Materiały źródłowe

• #1 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. Identifying patients with prognostically favorable disease is important, since they may derive substantial benefit, including prolonged survival, from directed treatment. In CUP cases, a focused search for the primary tumor is recommended. […] The criteria for CUP include a biopsy-proven malignancy for which the anatomic origin is unknown after a medical history has been obtained, a detailed physical examination has been performed, and liver and kidney function tests, blood tests, chest radiography, abdomen and pelvis computed tomography (CT), and mammography or a prostate-specific antigen (PSA) test have been performed.

• #2 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  Carcinoma of unknown primary (CUP) is a rare disease in which malignant (cancer) cells are found in the body but the place the cancer began is not known. […] Because the place where the cancer started is not known, many tests and procedures may be done to search for the primary cancer. […] If tests show there may be cancer, a biopsy is done. […] When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of CUP may be made. […] Tests and procedures used to find the primary cancer depend on where the cancer has spread. […] Sometimes the primary cancer is never found. […] The signs and symptoms of CUP are different, depending on where the cancer has spread in the body. […] Tests are done to find where the primary cancer began and to get information about where the cancer has spread. When tests are able to find the primary cancer, the cancer is no longer a CUP and treatment is based on the type of primary cancer.

• #3 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Patients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. […] A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). […] When dealing with a potential CUP diagnosis, clinical practice guidelines suggest a thorough diagnostic workup, which includes routine clinical evaluation, extensive physical examination, blood/biochemical analyses, and radiological tests.

• #4 Carcinoma of unknown primary – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/carcinoma-unknown-primary/symptoms-causes/syc-20370683

  Carcinoma of unknown primary is a diagnosis healthcare professionals give when they can’t find where a cancer started. A carcinoma of unknown primary is an advanced cancer that has spread in the body. […] In carcinoma of unknown primary, healthcare professionals find the metastatic cancer. But they can’t find the primary cancer. Carcinoma of unknown primary also is called occult primary cancer. […] Healthcare teams often use the kind of primary cancer you have to help decide on the treatment. If you’re found to have carcinoma of unknown primary, this piece of information is missing. Your healthcare team will work to find out what kind of cancer you have. […] The cause of carcinoma of unknown primary often isn’t known. Healthcare professionals use this diagnosis when they find signs of cancer that has spread but can’t find where the cancer started. The place where a cancer started growing is called the primary cancer.

• #5 Carcinoma of Unknown Primary (CUP): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6139-carcinoma-of-unknown-primary

  Carcinoma of unknown primary (CUP) is when cancer spreads from one area of your body, but healthcare providers cant find the original cancer. Providers treat carcinoma of unknown primary based on what they learn from tests. These tests indicate the most likely type of cancer. […] Healthcare providers diagnose carcinoma of unknown primary when they cant find the primary tumor. This can happen if the primary tumor was removed during an unrelated surgery or if tests dont detect it. […] Diagnosing CUP takes time. Healthcare providers first step is to try to identify the primary cancer. A provider will start that process by doing a physical examination. […] Initial tests to diagnose CUP may include: Complete blood count, Basic metabolic panel, Fecal occult blood test, Urinalysis. […] Your oncologist may do other tests as well, including: Imaging tests like CT scans, MRI and PET scans to see how far the cancer is spreading or where it may have started, Endoscopy to check your organs and tissues, Tumor marker test to look for signs of substances that certain kinds of cancer release into your blood.

• #6 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #7 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. Identifying patients with prognostically favorable disease is important, since they may derive substantial benefit, including prolonged survival, from directed treatment. In CUP cases, a focused search for the primary tumor is recommended. […] The criteria for CUP include a biopsy-proven malignancy for which the anatomic origin is unknown after a medical history has been obtained, a detailed physical examination has been performed, and liver and kidney function tests, blood tests, chest radiography, abdomen and pelvis computed tomography (CT), and mammography or a prostate-specific antigen (PSA) test have been performed.

• #8 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  Cancer of unknown primary (CUP) means that cancer has already spread, or metastasized, to other parts of the body, but doctors dont know where it started (called the primary site). So the focus of diagnosis is finding out the type of CUP, the primary site and all the places the cancer has spread. The process of diagnosis may seem long and frustrating. Its normal to worry, but try to remember that knowing where your cancer started can help your healthcare team decide on the best treatment options for you. […] An important early step in diagnosis is to try to find out the type of CUP. Different types of cells are found in different parts of the body. A pathologist will look at the cancer cells to try to identify the type of cell they started from. This can give the healthcare team clues to where the primary site might be.

• #9 Cancer of Unknown Primary Diagnosis | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/cancer-of-unknown-primary/cancer-of-unknown-primary-diagnosis.html

  With new scientific advances, doctors increasingly are able to find where cancer of unknown primary (CUP) began. In fact, now the primary site can be found in about four of five cases that originally were diagnosed as CUP. […] The first step in diagnosing CUP is a thorough history and physical examination. The doctor will ask you questions about your current and past health and risk factors, such as smoking or family history. […] If your doctor suspects cancer of unknown primary, one or more of the following tests may be done: […] Different methods are used to perform biopsies for CUP, depending on where the cancer is and the type of cancer. […] Staging is a way of determining how much disease is in the body and where it has spread. This information is important because it determines the type of treatment you will receive and the outlook for your recovery (prognosis). […] Cancer of unknown primary cannot be staged the way other cancers are because the origin of the primary cancer is not known. But doctors can make some predictions based on: […] MD Anderson patients have access to clinical trials offering promising new treatments that cannot be found anywhere else.

• #10 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  A complete family and personal medical history along with physical examination are essential in CUP cases, with attention to previous surgeries and lesions. A detailed pathologic examination of biopsied tissue is also mandatory and typically consists of hematoxylin-and-eosin staining and immunohistochemical tests. […] A fine-needle aspiration biopsy is usually sufficient in CUP cases, though a core biopsy may be performed if feasible. Biopsied tissue should first be evaluated by light microscopy with hematoxylin-and-eosin staining. […] Immunohistochemical markers, usually peroxidase-labeled antibodies against specific tumor antigens, are helpful in determining the tumor lineage. […] The role of positron emission tomography (PET) in the diagnostic algorithm of patients with disseminated (noncervical) CUP remains controversial, with most of the data being retrospective. […] A focused search for the primary tumor is recommended in CUP cases. Identifying patients with prognostically favorable disease is important, since they may have substantial benefit from directed treatment and experience prolonged survival.

• #11 Carcinoma of Unknown Primary – Clinical Tree

  https://clinicalpub.com/carcinoma-of-unknown-primary/

  Carcinoma of unknown primary is a diverse group of heterogeneous cancers that accounts for about 2% to 4% of all cancers. […] There is not universal agreement on the extent of the appropriate initial evaluation to find a primary cancer; a focused evaluation is recommended. […] Early biopsy of a metastatic site is recommended to establish the diagnosis and help direct further workup. […] Comprehensive history and physical examination (including breast and pelvic examinations in women and testis and prostate examinations in men) are essential. […] Routine laboratory tests, chestabdominalpelvic computed tomography scan, and mammography in women should be performed when indicated. […] Directed additional invasive tests should be based on symptomatology and pathologic evaluation of the tumor tissue.

• #12 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #13 Carcinoma of Unknown Primary (CUP): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6139-carcinoma-of-unknown-primary

  Carcinoma of unknown primary (CUP) is when cancer spreads from one area of your body, but healthcare providers cant find the original cancer. Providers treat carcinoma of unknown primary based on what they learn from tests. These tests indicate the most likely type of cancer. […] Healthcare providers diagnose carcinoma of unknown primary when they cant find the primary tumor. This can happen if the primary tumor was removed during an unrelated surgery or if tests dont detect it. […] Diagnosing CUP takes time. Healthcare providers first step is to try to identify the primary cancer. A provider will start that process by doing a physical examination. […] Initial tests to diagnose CUP may include: Complete blood count, Basic metabolic panel, Fecal occult blood test, Urinalysis. […] Your oncologist may do other tests as well, including: Imaging tests like CT scans, MRI and PET scans to see how far the cancer is spreading or where it may have started, Endoscopy to check your organs and tissues, Tumor marker test to look for signs of substances that certain kinds of cancer release into your blood.

• #14 Tests for a Cancer of Unknown Primary | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/how-diagnosed.html

  Cancers of unknown primary (CUP) are usually found as the result of signs or symptoms a person is having. However, when the primary tumor cannot be located, specialized pathologic and molecular tests can be used to help find where the cancer started. […] If your symptoms and the results of your physical exam suggest cancer, the doctor may use the following different types of tests to look for cancer, see what kind it is, and find out where it is located (and where it might have started): Imaging tests such as x-rays, ultrasound, CT (computed tomography) or MRI (magnetic resonance imaging) scans, Endoscopy exams to look at organs through a lighted tube placed into a body opening such as the mouth, nose, or anus, Blood tests, Biopsies to remove samples of tissues or cells and look at them with a microscope or test them in the lab.

• #15 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #16 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  Carcinoma of unknown primary (CUP) is a rare disease in which malignant (cancer) cells are found in the body but the place the cancer began is not known. […] Because the place where the cancer started is not known, many tests and procedures may be done to search for the primary cancer. […] If tests show there may be cancer, a biopsy is done. […] When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of CUP may be made. […] Tests and procedures used to find the primary cancer depend on where the cancer has spread. […] Sometimes the primary cancer is never found. […] The signs and symptoms of CUP are different, depending on where the cancer has spread in the body. […] Tests are done to find where the primary cancer began and to get information about where the cancer has spread. When tests are able to find the primary cancer, the cancer is no longer a CUP and treatment is based on the type of primary cancer.

• #17 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. Identifying patients with prognostically favorable disease is important, since they may derive substantial benefit, including prolonged survival, from directed treatment. In CUP cases, a focused search for the primary tumor is recommended. […] The criteria for CUP include a biopsy-proven malignancy for which the anatomic origin is unknown after a medical history has been obtained, a detailed physical examination has been performed, and liver and kidney function tests, blood tests, chest radiography, abdomen and pelvis computed tomography (CT), and mammography or a prostate-specific antigen (PSA) test have been performed.

• #18 Carcinoma of unknown primary – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/carcinoma-unknown-primary/diagnosis-treatment/drc-20433758

  To diagnose carcinoma of unknown primary, a healthcare professional might start by examining your body. Other procedures might include imaging tests and a biopsy. If your healthcare team finds carcinoma of unknown primary, they’ll do other tests to find the place where the cancer started. […] A biopsy is a procedure to remove a sample of tissue for testing in a lab. In the lab, tests can show whether cells in the tissue are cancerous. Other tests can show the kind of cells involved in the cancer. In carcinoma of unknown primary, tests show that the cancer cells spread from somewhere else. […] If a biopsy finds cells that spread from somewhere else, your healthcare team works to find where they started. The place where a cancer started growing is called the primary cancer. […] Tests to find the primary cancer might include: Physical exam. A healthcare professional might do a full body exam to look for signs of cancer. Imaging tests. Imaging tests might include CT and PET scans. Organ function tests. Blood tests that measure organ function tell the healthcare team how well the organs are working. The results might give the team clues about whether cancer might be affecting certain organs, such as the kidneys and liver. Tumor marker tests. Some cancers release proteins that can be detected in the blood. Tests to detect these proteins, called tumor marker tests, might help find the primary cancer. Examples of tumor marker tests include prostate-specific antigen test for prostate cancer and cancer antigen 125 test for ovarian cancer. Testing cancer cells in the lab. Healthcare professionals in the lab might run more tests on the cancer cells to get more clues about where they started. […] Sometimes these tests can find the primary cancer. If this happens, you no longer have carcinoma of unknown primary. For some people, the primary cancer is never found. If this happens, your healthcare team will use information from all of your tests to make a treatment plan.

• #19 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  The following tests are commonly used to try to find the primary site. After a health history, physical exam and basic imaging with CT scan, a biopsy is done. The results of these tests will help the healthcare team decide what other tests you may have. Your doctor may also order other tests to check your general health and to help plan your treatment. […] During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a lab. The report from the lab will confirm whether or not cancer cells are present in the sample. […] In the case of CUP, this biopsy tells doctors that there is cancer present, but they cant tell what kind of cancer it is. More biopsies may be done in some cases to try to find the primary site. […] Immunochemistry is an important part of diagnosis for CUP. It can help doctors identify the primary site and how aggressively the cancer behaves. This information helps doctors decide on the best treatment options and make a prognosis.

• #20 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  A complete family and personal medical history along with physical examination are essential in CUP cases, with attention to previous surgeries and lesions. A detailed pathologic examination of biopsied tissue is also mandatory and typically consists of hematoxylin-and-eosin staining and immunohistochemical tests. […] A fine-needle aspiration biopsy is usually sufficient in CUP cases, though a core biopsy may be performed if feasible. Biopsied tissue should first be evaluated by light microscopy with hematoxylin-and-eosin staining. […] Immunohistochemical markers, usually peroxidase-labeled antibodies against specific tumor antigens, are helpful in determining the tumor lineage. […] The role of positron emission tomography (PET) in the diagnostic algorithm of patients with disseminated (noncervical) CUP remains controversial, with most of the data being retrospective. […] A focused search for the primary tumor is recommended in CUP cases. Identifying patients with prognostically favorable disease is important, since they may have substantial benefit from directed treatment and experience prolonged survival.

• #21 Cancer of Unknown Primary Diagnosis | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/cancer-of-unknown-primary/cancer-of-unknown-primary-diagnosis.html

  With new scientific advances, doctors increasingly are able to find where cancer of unknown primary (CUP) began. In fact, now the primary site can be found in about four of five cases that originally were diagnosed as CUP. […] The first step in diagnosing CUP is a thorough history and physical examination. The doctor will ask you questions about your current and past health and risk factors, such as smoking or family history. […] If your doctor suspects cancer of unknown primary, one or more of the following tests may be done: […] Different methods are used to perform biopsies for CUP, depending on where the cancer is and the type of cancer. […] Staging is a way of determining how much disease is in the body and where it has spread. This information is important because it determines the type of treatment you will receive and the outlook for your recovery (prognosis). […] Cancer of unknown primary cannot be staged the way other cancers are because the origin of the primary cancer is not known. But doctors can make some predictions based on: […] MD Anderson patients have access to clinical trials offering promising new treatments that cannot be found anywhere else.

• #22 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  A complete family and personal medical history along with physical examination are essential in CUP cases, with attention to previous surgeries and lesions. A detailed pathologic examination of biopsied tissue is also mandatory and typically consists of hematoxylin-and-eosin staining and immunohistochemical tests. […] A fine-needle aspiration biopsy is usually sufficient in CUP cases, though a core biopsy may be performed if feasible. Biopsied tissue should first be evaluated by light microscopy with hematoxylin-and-eosin staining. […] Immunohistochemical markers, usually peroxidase-labeled antibodies against specific tumor antigens, are helpful in determining the tumor lineage. […] The role of positron emission tomography (PET) in the diagnostic algorithm of patients with disseminated (noncervical) CUP remains controversial, with most of the data being retrospective. […] A focused search for the primary tumor is recommended in CUP cases. Identifying patients with prognostically favorable disease is important, since they may have substantial benefit from directed treatment and experience prolonged survival.

• #23 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  An accurate pathological assessment of biopsy material is essential in the initial evaluation of the patient with suspected CUP. […] The initial pathological assessment of the biopsy specimen is by light microscopic examination of paraffin sections stained with hematoxylin and eosin. […] Immunohistochemical markers play a significant role in the diagnosis and workup of CUP. […] The potential role of serum tumor markers in the evaluation and management of patients with CUP has been reviewed. […] The laboratory evaluation of patients with suspected CUP should begin with a complete blood count to screen for anemia. […] Bilateral mammography should be a part of the routine evaluation of most women with CUP. […] Computed tomography (CT) of the abdomen and pelvis is routinely performed as part of the diagnostic evaluation of CUP to locate the primary tumor, to evaluate the extent of disease, and to select the most favorable biopsy site.

• #24 Tests for a Cancer of Unknown Primary | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/how-diagnosed.html

  Physical exams, imaging tests, and blood tests can sometimes strongly suggest a cancer is present, but in most cases a biopsy (removing some of the tumor for viewing with a microscope and other lab testing) is needed to know for certain that cancer is present. A biopsy is also usually needed to tell what kind of cancer it is (like adenocarcinoma or squamous cell carcinoma) and can give clues about where the cancer started. A biopsy is needed to diagnose CUP. […] After initial lab tests, the pathologist classifies a cancer of unknown primary into 1 of the 5 main types: Squamous cell carcinoma, Adenocarcinoma, Poorly differentiated carcinoma, Neuroendocrine carcinoma.

• #25 Cancer of Unknown Primary: Diagnosis

  https://healthinfo.universityhealthsystem.com/Library/TestsProcedures/Neurological/34,BCUPD3

  You may have 1 or more of these tests to look for the primary site and spread of CUP: Urine and blood tests, Imaging tests, Biopsy and tissue tests. […] A biopsy is a test to take tiny pieces of tissue, called samples, from your body. If fluid has collected where it shouldn’t, like in the space around your lung, it can be taken out, too. A pathologist tests the tissue or fluid for signs of cancer. The way the cells look and the lab test results can help healthcare providers tell where the cancer started. […] If the primary site, or the place the cancer started, can’t be found after many tests, you may be diagnosed with cancer of unknown primary. A pathologist will review your biopsy samples. They will then classify the cancer as 1 of these 5 most common types: Squamous cell carcinoma, Adenocarcinoma, Poorly differentiated carcinoma, Neuroendocrine carcinoma, Poorly differentiated malignant neoplasm. […] This classification will help your provider decide on a treatment plan, even if the primary site of the cancer isn’t known.

• #26 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  A complete family and personal medical history along with physical examination are essential in CUP cases, with attention to previous surgeries and lesions. A detailed pathologic examination of biopsied tissue is also mandatory and typically consists of hematoxylin-and-eosin staining and immunohistochemical tests. […] A fine-needle aspiration biopsy is usually sufficient in CUP cases, though a core biopsy may be performed if feasible. Biopsied tissue should first be evaluated by light microscopy with hematoxylin-and-eosin staining. […] Immunohistochemical markers, usually peroxidase-labeled antibodies against specific tumor antigens, are helpful in determining the tumor lineage. […] The role of positron emission tomography (PET) in the diagnostic algorithm of patients with disseminated (noncervical) CUP remains controversial, with most of the data being retrospective. […] A focused search for the primary tumor is recommended in CUP cases. Identifying patients with prognostically favorable disease is important, since they may have substantial benefit from directed treatment and experience prolonged survival.

• #27 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  The following tests are commonly used to try to find the primary site. After a health history, physical exam and basic imaging with CT scan, a biopsy is done. The results of these tests will help the healthcare team decide what other tests you may have. Your doctor may also order other tests to check your general health and to help plan your treatment. […] During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a lab. The report from the lab will confirm whether or not cancer cells are present in the sample. […] In the case of CUP, this biopsy tells doctors that there is cancer present, but they cant tell what kind of cancer it is. More biopsies may be done in some cases to try to find the primary site. […] Immunochemistry is an important part of diagnosis for CUP. It can help doctors identify the primary site and how aggressively the cancer behaves. This information helps doctors decide on the best treatment options and make a prognosis.

• #28 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Sometimes, however, even when doctors use very sophisticated methods to try to identify the primary site, the part of the body the cancer cells came from cannot be determined. About 2 to 4 percent of all cancer patients have a cancer whose primary site is never found. Identifying the primary tumor site is important because knowing its location and type often helps doctors plan the best treatment. […] Immunohistochemistry including cytokeratin 7 and cytokeratin 20 can give a clue about possible origins of carcinomas of unknown primary site. […] CUP may be classified by its appearance under a light microscope. The majority of cancers of unknown primary, about 90%, are adenocarcinomas, with 60% appearing as moderately to well-differentiated adenocarcinoma, while about 30% are poorly differentiated adenocarcinoma.

• #29 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Once the epithelial origin is established, the expression of two keratins, K7 and K20, which broadly define the subsets of carcinoma, is mostly used for CUP primary site predictions. […] International guidelines for tumor treatment are essentially based on primary site definition. With no evidence of a primary site, CUP patients cannot be treated with site-specific therapy; thus, they are managed based on their clinicopathological characteristics. […] An indication of a site of origin in these patients, or an approach based on personalized medicine, may assist the physicians in the selection of the best treatment options, potentially improving CUPs prognosis and survival.

• #30 Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11563-1

  Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. […] The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). […] Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. […] Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. […] P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas.

• #31 Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11563-1

  We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. […] The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. […] Molecular testing is also predictive of survival rates. […] Identification of the primary tumor site is pivotal for the treatment and prognosis of patients with CUP. […] Various panels of IHC markers have been employed on the basis of morphological findings for the identification of the CUP primary sites, particularly in poorly differentiated or undifferentiated tumors. […] However, previous studies have revealed accurate identification by IHC analysis in only 5065% of metastatic cancers. […] Our results demonstrated no diagnostic value of IHC testing in the identification of primary tumors in approximately half of all patients.

• #32 Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling – PubMed

  https://pubmed.ncbi.nlm.nih.gov/22987975/

  Carcinoma of unknown primary (CUP) remains a common and challenging clinical problem. The aim of diagnostic work-up in CUP is to classify as specifically as possible the cancer affecting the patient, according to the broad tumour type, subtype and, where possible, site of origin. This classification currently best predicts patient outcome and guides optimal treatment. a stepwise approach to diagnostic work-up is described. although pathology is based on morphology, the assessment of tissue-specific genes through immunohistochemistry (IHC) substantially helps tumour classification at each diagnostic step. […] For IHC in CUP, recent improvements include more standardised approaches and marker panels plus new markers. Tissue-specific genes are also being used in CUP work-up through molecular profiling. Large-scale profiles of hundreds of tumours of different types have been generated, compared and used to generate diagnostic algorithms. Commercial tests for CUP classification have been developed at the mRNa and microRNA and (miRNA) levels and validated in metastatic tumours and CUPs. While currently optimal pathology and IHC remain the 'gold standard’ for CUP diagnostic work-up, and full clinical correlation is vital, the molecular tests appear to perform well: in the main diagnostic challenge of undifferentiated or poorly differentiated tumours, molecular profiling performs as well as or better than IHC.

• #33 Tests for cancer of unknown primary (CUP) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/cancer-unknown-primary-cup/getting-diagnosed/tests-cancer-unknown-primary-cup

  Cancer of unknown primary (CUP) means that there are cancer cells in your body but your doctors dont know where the cancer started. The tests you have to help diagnose CUP depend on your symptoms and where in your body the cancer is. […] You have a number of tests to try to find out the cause of your symptoms. If tests show that you have secondary cancer, then you usually have more tests to try to find out where the cancer started. You have a confirmed cancer of unknown primary (cCUP) if doctors cant find the primary cancer after having the tests. […] Your specialist usually does more tests. These might include: taking a sample of tissue called a biopsy, CT scan, MRI scan, ultrasound scan, PET-CT scan, tumour marker tests. […] A biopsy means taking a sample of tissue so that it can be looked at under a microscope. This is the only way to find out if an abnormal area is cancer or not.

• #34 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  Tumour markers are substances in the blood that may mean cancer is present. Tumour marker tests are generally used to check your response to cancer treatment. They can also be used to help find the primary tumour in a person with CUP and can guide which other tests may be done. […] A CT scan is used to look at the head and neck, chest, abdomen and pelvis for any evidence of the primary site. Doctors will use other tests, such as a biopsy, to examine any abnormal areas found with a CT scan. […] An endoscopy allows a doctor to look inside the body cavities using a tube with a light and lens on the end (called an endoscope). During an endoscopy, the doctor can also take samples from any abnormal areas. A pathologist examines the samples to see if it is cancer, which can help the healthcare team identify the primary site.

• #35 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  A complete family and personal medical history along with physical examination are essential in CUP cases, with attention to previous surgeries and lesions. A detailed pathologic examination of biopsied tissue is also mandatory and typically consists of hematoxylin-and-eosin staining and immunohistochemical tests. […] A fine-needle aspiration biopsy is usually sufficient in CUP cases, though a core biopsy may be performed if feasible. Biopsied tissue should first be evaluated by light microscopy with hematoxylin-and-eosin staining. […] Immunohistochemical markers, usually peroxidase-labeled antibodies against specific tumor antigens, are helpful in determining the tumor lineage. […] The role of positron emission tomography (PET) in the diagnostic algorithm of patients with disseminated (noncervical) CUP remains controversial, with most of the data being retrospective. […] A focused search for the primary tumor is recommended in CUP cases. Identifying patients with prognostically favorable disease is important, since they may have substantial benefit from directed treatment and experience prolonged survival.

• #36 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  Positron emission tomography with 18fluoro-2-deoxy-d-glucose (18F-FDG-PET) is a noninvasive nuclear imaging technique that has been proven to be a valuable diagnostic tool in identifying primary malignant tumors and the extent of metastatic disease. […] The premise for studying the role of molecular profiling in CUP cancers is that metastatic tumors have molecular signatures that match their tissue of origin. […] The MD Anderson Cancer Center, in collaboration with our colleagues at Sarah Cannon Cancer Center, reported the first large CUP series that evaluated the feasibility of a 10-gene RT-PCR assay to identify the ToO in CUP patients. […] There are several challenges in the field of molecular profiling and CUP. […] Given the heterogeneity of the CUP cancers, it is difficult to interpret clinical trials and definite benefit of any particular combination in CUP cancers.

• #37 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  Tumour markers are substances in the blood that may mean cancer is present. Tumour marker tests are generally used to check your response to cancer treatment. They can also be used to help find the primary tumour in a person with CUP and can guide which other tests may be done. […] A CT scan is used to look at the head and neck, chest, abdomen and pelvis for any evidence of the primary site. Doctors will use other tests, such as a biopsy, to examine any abnormal areas found with a CT scan. […] An endoscopy allows a doctor to look inside the body cavities using a tube with a light and lens on the end (called an endoscope). During an endoscopy, the doctor can also take samples from any abnormal areas. A pathologist examines the samples to see if it is cancer, which can help the healthcare team identify the primary site.

• #38 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  The following tests and procedures may be done to find where the cancer first began: CT scan (CAT scan), MRI (magnetic resonance imaging), PET scan (positron emission tomography scan), Mammogram, Endoscopy, Tumor marker test. […] Sometimes, none of the tests can find the primary cancer site. In these cases, treatment may be based on what the doctor thinks is the most likely type of cancer. […] The prognosis depends on the following: Where the cancer began in the body and where it has spread, The number of organs with cancer in them, The way the tumor cells look when viewed under a microscope, Whether the patient is male or female, Whether the cancer has just been diagnosed or has recurred (come back). […] There are different types of treatment for patients with carcinoma of unknown primary (CUP).

• #39 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #40 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  The U.S. Food and Drug Administration (FDA) has approved some novel targeted therapies when a molecular target is identified in a cancer, regardless of primary site (including when no primary site is evident with metastases). […] A meta-analysis of five studies including 1,114 patients compared site-specific therapy from genomic profiling versus empiric therapy. […] In a retrospective analysis, a cohort of 97 patients with CUP underwent NGS of tissue- or blood-derived cell-free DNA. […] The median number of pathogenic genomic alterations found in tissue was four (range, 0-25), and the median number of genomic alterations found in cfDNA was two (range, 0-9). […] The presence of elevated serum or tissue levels of AFP and/or beta-hCG suggests testicular cancer or extragonadal germ cell tumor in males.

• #41 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #42 Unknown Primary Carcinomas: Diagnosis and Management

  https://www.cancernetwork.com/view/unknown-primary-carcinomas-diagnosis-and-management

  The role of tumor markers in the evaluation of patients with unknown primary tumors is unclear. Most tumor markers are nonspecific, and they may be most useful in monitoring a patient’s response to therapy. Tumor markers do not appear to be predictive of response to chemotherapy, but their directed use seems valuable in complementing the overall evaluation of patients with unknown primary cancers. […] Using the diagnostic approach outlined, it is possible to detect a primary neoplasm in 20% to 30% of patients presenting with unknown primary malignancies. […] It is clearly inappropriate to think of all patients with unknown primary neoplasms as having an untreatable disease and a poor outlook. Significant benefit may be achieved by administering regional or specific systemic therapies, and many of these patients can expect a prolonged survival. All patients should undergo a directed diagnostic evaluation for the primary tumor.

• #43 Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling – PubMed

  https://pubmed.ncbi.nlm.nih.gov/22987975/

  Carcinoma of unknown primary (CUP) remains a common and challenging clinical problem. The aim of diagnostic work-up in CUP is to classify as specifically as possible the cancer affecting the patient, according to the broad tumour type, subtype and, where possible, site of origin. This classification currently best predicts patient outcome and guides optimal treatment. a stepwise approach to diagnostic work-up is described. although pathology is based on morphology, the assessment of tissue-specific genes through immunohistochemistry (IHC) substantially helps tumour classification at each diagnostic step. […] For IHC in CUP, recent improvements include more standardised approaches and marker panels plus new markers. Tissue-specific genes are also being used in CUP work-up through molecular profiling. Large-scale profiles of hundreds of tumours of different types have been generated, compared and used to generate diagnostic algorithms. Commercial tests for CUP classification have been developed at the mRNa and microRNA and (miRNA) levels and validated in metastatic tumours and CUPs. While currently optimal pathology and IHC remain the 'gold standard’ for CUP diagnostic work-up, and full clinical correlation is vital, the molecular tests appear to perform well: in the main diagnostic challenge of undifferentiated or poorly differentiated tumours, molecular profiling performs as well as or better than IHC.

• #44 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  Cancers of unknown primary (CUP) origin account for 3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. […] Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. […] With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. […] Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. […] The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

• #45 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  Accurate prediction of the tissue of origin using immunohistochemical staining and/or gene expression profiling is now possible in certain CUP cases. Appropriate classification, based upon all available evidence, is essential to identify patients for whom a specific treatment may be particularly useful and site-specific therapy based on these predictions is replacing empiric chemotherapy as the new treatment standard (J. Hainsworth F. Greco, 2023). […] Presently, patients are initially placed into one of four categories (adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma, poorly differentiated) based upon the light microscopic examination of the initial biopsy. This classification is then used to guide further evaluation as indicated below (J. D. Hainsworth F. A. Greco, 2023):

• #46 Molecular Diagnostic Classification for Cancers of Unknown Primary (CUP): Post-Testing Diagnosis and Treatment Impact Analysis From Real-World Claims Data – Tempus

  https://www.tempus.com/publications/molecular-diagnostic-classification-for-cancers-of-unknown-primary-cup-post-testing-diagnosis-and-treatment-impact-analysis-from-real-world-claims-data/?srsltid=AfmBOopnIPbfY79RQmglbX8BoK-sxZNYM4T8Rx-072n8fccwkdfYf0-O

  Molecular Diagnostic Classification for Cancers of Unknown Primary (CUP): Post-Testing Diagnosis and Treatment Impact Analysis From Real-World Claims Data […] Background: Next-generation sequencing-based molecular diagnostic classifiers can help identify the tissue of origin for CUP, and enable the selection of site-specific therapies (as opposed to empiric chemotherapy) for this vulnerable population with high unmet need. NCCN guidelines do not endorse the use of tissue of origin classifiers as standard of care for CUP patients due to limited clinical evidence. Here, we linked results of a commercial molecular diagnostic classifier with claims data to understand how this test impacted patient care. […] Methods: We assessed de-identified claims data from the Komodo Healthcare Map (a database including provider visits, laboratory tests, procedures, imaging, and prescriptions) linked to the Tempus Tumor Origin (TO) test a machine learning classifier that uses RNA-seq data to classify tumors into one of 68 histological subtypes. Eligible patients had pathologist-confirmed CUP and were classified as one of 9 subtypes (each having n10). Impact was determined by identifying either one or more new diagnostic codes or new subtype-related medication claims following TO testing.

• #47 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  Cancers of unknown primary (CUP) origin account for 3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. […] Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. […] With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. […] Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. […] The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

• #48 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  CUPLR comprises an ensemble of binary random forest classifiers that each discriminate one of 35 cancer types with an overall recall of 90%. […] We find that while RMD and mutational signatures were highly predictive of cancer type, the incorporation of SV features improves prediction performance for cancer types that currently lack highly informative features. […] Furthermore, we have ensured that the output of CUPLR, namely the prediction probabilities and the features supporting each prediction, are humanly interpretable to facilitate diagnostic use and clinical decision-making with CUPLR. […] We thus demonstrate that CUPLR can potentially clarify the TOO for over half of patients with CUP.

• #49 Molecular Diagnostic Classification for Cancers of Unknown Primary (CUP): Post-Testing Diagnosis and Treatment Impact Analysis From Real-World Claims Data – Tempus

  https://www.tempus.com/publications/molecular-diagnostic-classification-for-cancers-of-unknown-primary-cup-post-testing-diagnosis-and-treatment-impact-analysis-from-real-world-claims-data/?srsltid=AfmBOopnIPbfY79RQmglbX8BoK-sxZNYM4T8Rx-072n8fccwkdfYf0-O

  Molecular Diagnostic Classification for Cancers of Unknown Primary (CUP): Post-Testing Diagnosis and Treatment Impact Analysis From Real-World Claims Data […] Background: Next-generation sequencing-based molecular diagnostic classifiers can help identify the tissue of origin for CUP, and enable the selection of site-specific therapies (as opposed to empiric chemotherapy) for this vulnerable population with high unmet need. NCCN guidelines do not endorse the use of tissue of origin classifiers as standard of care for CUP patients due to limited clinical evidence. Here, we linked results of a commercial molecular diagnostic classifier with claims data to understand how this test impacted patient care. […] Methods: We assessed de-identified claims data from the Komodo Healthcare Map (a database including provider visits, laboratory tests, procedures, imaging, and prescriptions) linked to the Tempus Tumor Origin (TO) test a machine learning classifier that uses RNA-seq data to classify tumors into one of 68 histological subtypes. Eligible patients had pathologist-confirmed CUP and were classified as one of 9 subtypes (each having n10). Impact was determined by identifying either one or more new diagnostic codes or new subtype-related medication claims following TO testing.

• #50 Molecular Diagnostic Classification for Cancers of Unknown Primary (CUP): Post-Testing Diagnosis and Treatment Impact Analysis From Real-World Claims Data – Tempus

  https://www.tempus.com/publications/molecular-diagnostic-classification-for-cancers-of-unknown-primary-cup-post-testing-diagnosis-and-treatment-impact-analysis-from-real-world-claims-data/?srsltid=AfmBOopnIPbfY79RQmglbX8BoK-sxZNYM4T8Rx-072n8fccwkdfYf0-O

  Results: We analyzed data from 490 patients: 483 for the diagnosis analysis and 213 for the medication analysis (206 patients appear in both, due to differences in timing of diagnosis vs. medication claims). We found that post-TO testing, 49.9% (n=241) of patients had a diagnostic code change, 63.8% (n=136) had a treatment change, and 41% (n=85) had both. In total, 59.6% (n=292) of patients were impacted by the use of this classifier, with variation according to predicted subtype. Cancer types with specific treatment options were more likely to have changes in diagnostic code or treatment. For CUP predicted as lung adenocarcinomas, 85% of the cases had a new subtype-aligned medication, and 78% were specifically placed on immunotherapy (IO) compared with 24% of overall patients. […] Conclusions: Using real-world claims data, we show that molecular diagnostic testing utilizing Tempus TO impacted care for a majority of CUP patients. This cohort will be followed to identify how TO testing decisions impact outcomes.

• #51 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  The NCCN lists two primary applications of molecular profiling in management of CUP; using gene expression profiling and molecular cancer classifier assays to determine tissue of origin for site-specific therapy, and identifying actionable mutations for targeted therapy (NCCN, 2024). […] The 2023 NCCN guidelines for the workup of an occult primary malignancy address the use of molecular methods in the classification of tumors. The guidelines state Gene sequencing to predict tissue of origin is not recommended. […] Overall, the NCCN states that the clinical benefit of using molecular profiling to guide treatment decisions in CUP remains to be determined. […] A 2010 clinical guideline from NICE, which was reaffirmed in 2017, recommended against the use of gene expression-based profiling to identify primary tumors in patients with provisional CUPs.

• #52 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  In 2023, EMSO updated their clinical practice guidelines for the diagnosis, treatment, and follow-up of cancer of unknown primary. The guideline states that The clinical utility of gene expression profiling to help elucidate the likely primary is not currently supported by high-level evidence. […] The NCI acknowledges the possible utility of gene expression profiling and next generation sequencing to identify a potential site of origin in patients with CUP (NCI, 2023). […] The American Cancer Society acknowledges the possible use of gene expression profiling and molecule genetic testing for the diagnosis of cancers of unknown primary. However, they note that molecular genetic testing is not needed in most cases, but its sometimes helpful in classifying some cancers when other tests have not provided clues regarding their origin.

• #53 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Based on the classification and the location of the metastatic cancer of unknown primary, doctors decide which additional tests should be done. […] The classification and location also help the doctor decide what other imaging tests may be helpful in looking for the primary site. […] Tests will be done to look at these areas thoroughly for signs of where the cancer may have started. […] Imaging tests like CT or MRI scans of the sinuses and neck area may be used to look for small cancers that may have already spread to lymph nodes in the neck. […] If a breast cancer diagnosis cannot be confirmed, tests to look for lung cancer may be done. […] Tests for CA-125 in the blood and tumor samples are positive in most ovarian and fallopian tube cancers, and can be used to help determine whether the primary tumor is likely to be from there or some other organ.

• #54 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Results of blood tests and stains of the cancer cells for alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are often positive in germ cell tumors. […] Its important to identify germ cell tumors because they often respond well to certain combinations of chemotherapy drugs with good outcomes and sometimes, cures. […] Treatment of melanoma depends on whether it has spread only to lymph nodes or whether internal organs are also involved. […] The main goal in trying to determine the source of a CUP is to see if you have a cancer that may respond well to specific treatments. […] Tests of the cancer cells for thyroglobulin can identify many thyroid cancers, which are often effectively treated with radioactive iodine injections. […] A type of poorly differentiated malignant neoplasm called small cell carcinoma or poorly differentiated neuroendocrine carcinoma can develop in the lungs and, less often, in other organs.

• #55 Adenocarcinoma of unknown primary site – UpToDate

  https://www.uptodate.com/contents/adenocarcinoma-of-unknown-primary-site

  Adenocarcinoma of unknown primary site […] Cancer of unknown primary site (CUP) is a relatively common clinical entity, accounting for approximately 2 percent of all invasive cancers. CUP is diagnosed in patients with metastatic cancer, but no anatomic primary site identified on a comprehensive initial evaluation. Cancers from many primary sites with varying biology are represented in patients with CUP. In many patients with CUP, improved diagnostic methods such as molecular cancer classifier assays (MCCAs; also known as gene expression profile assays) and immunohistochemistry (IHC) staining can predict the site of tumor origin. However, patients with CUP remain a clinically distinct group since the anatomic primary site is usually not detected during the clinical course. The diagnosis and management of patients with adenocarcinoma of unknown primary site are reviewed here. The diagnosis and management of the other CUPs are discussed separately.

• #56 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Sometimes, however, even when doctors use very sophisticated methods to try to identify the primary site, the part of the body the cancer cells came from cannot be determined. About 2 to 4 percent of all cancer patients have a cancer whose primary site is never found. Identifying the primary tumor site is important because knowing its location and type often helps doctors plan the best treatment. […] Immunohistochemistry including cytokeratin 7 and cytokeratin 20 can give a clue about possible origins of carcinomas of unknown primary site. […] CUP may be classified by its appearance under a light microscope. The majority of cancers of unknown primary, about 90%, are adenocarcinomas, with 60% appearing as moderately to well-differentiated adenocarcinoma, while about 30% are poorly differentiated adenocarcinoma.

• #57 Unknown Primary Squamous Cell Cancer (Evaluation and Management) | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/unknown-primary-squamous-cell-cancer-evaluation-and-management

  The „unknown primary” refers to cancer identified in the neck suspected to represent metastasis from a primary site not readily determined. This discussion is limited to squamous cell carcinoma. […] Unknown primary represents about 1-2% of head and neck squamous cell cancers. […] The incidence of unknown primary cancers has diminished with the advent of advanced radiographic imaging (CT, MRI, PET) and routing use of flexible fiberoptic endoscopic examination in the clinic. […] With increased incidence and recognition of the impact of human papillomavirus (HPV), unknown primary cancers are increasingly identified as oropharyngeal tumors. […] The working diagnosis is cervical lymphadenitis. […] Persistence after single course of antibiotics warrants pathologic assessment. […] The FNA diagnosis of squamous cell carcinoma is generally uncomplicated.

• #58 Carcinoma of Unknown Primary: Diagnostics and the Potential of Transoral Surgery | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_12

  The topic of the unknown primary tumour in head and neck cancer (CUP) has been extensively studied. The increasing incidence of Human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) as well as the emerging role of transoral robotic surgery (TORS) has led to revision and evolution of diagnostic and treatment paradigms. The concept of tongue base mucosectomy (TBM) has gained its place in the diagnostic pathway. […] Since identification of the primary tumour has implications for treatment and prognosis, the interest in improvement of diagnostics and surgery is growing. […] Currently, it is general practice to at least perform p16 immunohistochemistry (IHC) after FNA or CNB in case of proven cervical metastasis of SCC. […] Algorithms for CUP over the past 5 years have shown increasing uniformity with a prominent role for tongue base mucosectomy (TBM), also called lingual tonsillectomy (LT) in HPV-positive CUP.

• #59 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Cancer of unknown primary origin (CUP) is a cancer that is determined to be at the metastatic stage at the time of diagnosis, but a primary tumor cannot be identified. A diagnosis of CUP requires a clinical picture consistent with metastatic disease and one or more biopsy results inconsistent with a tumor cancer. […] In recent years, microscopic and other diagnostic techniques have improved dramatically. However, the tissue of origin can be still determined only about in one in four cases of CUPs with these methods. […] The initial work-up of a cancer of unknown primary includes a CT scan of the chest, abdomen, and pelvis, with IV contrast. […] When the cancer cells are poorly differentiated (that is, they look less evolved than normal cells when viewed under a microscope), the cancer may be either a lymphoma or a germ cell tumor.

• #60 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  When the type of cancer cells or tissue removed is different from the type of cancer cells expected to be found, a diagnosis of CUP may be made. […] The following tests and procedures may be used: Physical exam and health history, Urinalysis, Blood chemistry studies, Complete blood count, Fecal occult blood test. […] A biopsy is the removal of cells or tissues so they can be viewed under a microscope by a pathologist. […] If cancer is found, one or more of the following laboratory tests may be used to study the tissue samples and find out the type of cancer: Genetic analysis, Histologic study, Immunohistochemistry, Reverse transcription-polymerase chain reaction (RT-PCR) test, Cytogenetic analysis, Light and electron microscopy. […] In some cases, the part of the body where cancer cells are first found helps the doctor decide which diagnostic tests will be most helpful.

• #61 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Results of blood tests and stains of the cancer cells for alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are often positive in germ cell tumors. […] Its important to identify germ cell tumors because they often respond well to certain combinations of chemotherapy drugs with good outcomes and sometimes, cures. […] Treatment of melanoma depends on whether it has spread only to lymph nodes or whether internal organs are also involved. […] The main goal in trying to determine the source of a CUP is to see if you have a cancer that may respond well to specific treatments. […] Tests of the cancer cells for thyroglobulin can identify many thyroid cancers, which are often effectively treated with radioactive iodine injections. […] A type of poorly differentiated malignant neoplasm called small cell carcinoma or poorly differentiated neuroendocrine carcinoma can develop in the lungs and, less often, in other organs.

• #62 Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11563-1

  The sensitivity of INSM1 was found to be 80.0%, thus indicating its role as a valuable marker of neuroendocrine differentiation in both primary and metastatic neuroendocrine neoplasms. […] We propose a diagnostic strategy using highly sensitive markers including TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing for identification of primary tumor sites in clinical practice. […] Canhelp-Origin molecular testing can identify the tissue of origin in most CUPs, and thus serve as a prognostic factor.

• #63 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Based on the classification and the location of the metastatic cancer of unknown primary, doctors decide which additional tests should be done. […] The classification and location also help the doctor decide what other imaging tests may be helpful in looking for the primary site. […] Tests will be done to look at these areas thoroughly for signs of where the cancer may have started. […] Imaging tests like CT or MRI scans of the sinuses and neck area may be used to look for small cancers that may have already spread to lymph nodes in the neck. […] If a breast cancer diagnosis cannot be confirmed, tests to look for lung cancer may be done. […] Tests for CA-125 in the blood and tumor samples are positive in most ovarian and fallopian tube cancers, and can be used to help determine whether the primary tumor is likely to be from there or some other organ.

• #64 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Based on the classification and the location of the metastatic cancer of unknown primary, doctors decide which additional tests should be done. […] The classification and location also help the doctor decide what other imaging tests may be helpful in looking for the primary site. […] Tests will be done to look at these areas thoroughly for signs of where the cancer may have started. […] Imaging tests like CT or MRI scans of the sinuses and neck area may be used to look for small cancers that may have already spread to lymph nodes in the neck. […] If a breast cancer diagnosis cannot be confirmed, tests to look for lung cancer may be done. […] Tests for CA-125 in the blood and tumor samples are positive in most ovarian and fallopian tube cancers, and can be used to help determine whether the primary tumor is likely to be from there or some other organ.

• #65 Unknown Primary Squamous Cell Cancer (Evaluation and Management) | Iowa Head and Neck Protocols

  https://medicine.uiowa.edu/iowaprotocols/unknown-primary-squamous-cell-cancer-evaluation-and-management

  The „unknown primary” refers to cancer identified in the neck suspected to represent metastasis from a primary site not readily determined. This discussion is limited to squamous cell carcinoma. […] Unknown primary represents about 1-2% of head and neck squamous cell cancers. […] The incidence of unknown primary cancers has diminished with the advent of advanced radiographic imaging (CT, MRI, PET) and routing use of flexible fiberoptic endoscopic examination in the clinic. […] With increased incidence and recognition of the impact of human papillomavirus (HPV), unknown primary cancers are increasingly identified as oropharyngeal tumors. […] The working diagnosis is cervical lymphadenitis. […] Persistence after single course of antibiotics warrants pathologic assessment. […] The FNA diagnosis of squamous cell carcinoma is generally uncomplicated.

• #66 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Based on the classification and the location of the metastatic cancer of unknown primary, doctors decide which additional tests should be done. […] The classification and location also help the doctor decide what other imaging tests may be helpful in looking for the primary site. […] Tests will be done to look at these areas thoroughly for signs of where the cancer may have started. […] Imaging tests like CT or MRI scans of the sinuses and neck area may be used to look for small cancers that may have already spread to lymph nodes in the neck. […] If a breast cancer diagnosis cannot be confirmed, tests to look for lung cancer may be done. […] Tests for CA-125 in the blood and tumor samples are positive in most ovarian and fallopian tube cancers, and can be used to help determine whether the primary tumor is likely to be from there or some other organ.

• #67 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  Women with peritoneal carcinomatosis of an undifferentiated adenocarcinoma or serous histology in the absence of an ovarian, fallopian tube, or uterine primary site should undergo diagnostic testing and a therapeutic approach for ovarian cancer. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile. […] Immunological therapy using checkpoint inhibitors such as nivolumab has been given to a general population with unfavorable CUP, resulting in a 22% overall response rate. […] Patients with unfavorable CUP who are not candidates for molecular targeted therapy or immunotherapy are candidates for clinical trials. […] Cytotoxic chemotherapy can be a palliative therapy, but the choice of drugs has been based on a few small clinical studies, with no randomized trials establishing their benefit over best supportive care.

• #68 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Results of blood tests and stains of the cancer cells for alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are often positive in germ cell tumors. […] Its important to identify germ cell tumors because they often respond well to certain combinations of chemotherapy drugs with good outcomes and sometimes, cures. […] Treatment of melanoma depends on whether it has spread only to lymph nodes or whether internal organs are also involved. […] The main goal in trying to determine the source of a CUP is to see if you have a cancer that may respond well to specific treatments. […] Tests of the cancer cells for thyroglobulin can identify many thyroid cancers, which are often effectively treated with radioactive iodine injections. […] A type of poorly differentiated malignant neoplasm called small cell carcinoma or poorly differentiated neuroendocrine carcinoma can develop in the lungs and, less often, in other organs.

• #69 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  Women with peritoneal carcinomatosis of an undifferentiated adenocarcinoma or serous histology in the absence of an ovarian, fallopian tube, or uterine primary site should undergo diagnostic testing and a therapeutic approach for ovarian cancer. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile. […] Immunological therapy using checkpoint inhibitors such as nivolumab has been given to a general population with unfavorable CUP, resulting in a 22% overall response rate. […] Patients with unfavorable CUP who are not candidates for molecular targeted therapy or immunotherapy are candidates for clinical trials. […] Cytotoxic chemotherapy can be a palliative therapy, but the choice of drugs has been based on a few small clinical studies, with no randomized trials establishing their benefit over best supportive care.

• #70 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  Women with peritoneal carcinomatosis of an undifferentiated adenocarcinoma or serous histology in the absence of an ovarian, fallopian tube, or uterine primary site should undergo diagnostic testing and a therapeutic approach for ovarian cancer. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile. […] Immunological therapy using checkpoint inhibitors such as nivolumab has been given to a general population with unfavorable CUP, resulting in a 22% overall response rate. […] Patients with unfavorable CUP who are not candidates for molecular targeted therapy or immunotherapy are candidates for clinical trials. […] Cytotoxic chemotherapy can be a palliative therapy, but the choice of drugs has been based on a few small clinical studies, with no randomized trials establishing their benefit over best supportive care.

• #71 Adenocarcinoma of unknown primary site – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/791

  Adenocarcinoma of unknown primary site is a common clinical entity, comprising 2% to 4% of all incident cancers worldwide. […] A key goal in the diagnostic workup is to identify subsets of patients with a more favorable clinicopathologic subtype and likely better outcome. […] Adenocarcinoma of unknown primary site (AUP) is the major subgroup in the common clinical entity of cancer of unknown primary site (CUP). It is defined as metastatic adenocarcinoma for which the primary site is undetectable at presentation, despite thorough physical exam, and laboratory and radiographic investigation. […] Key diagnostic factors include bone pain and family history of cancer. […] Other diagnostic factors include jaundice, ascites, personal history of previous cancer, history of smoking, pain, palpable mass, symptoms of postobstructive pneumonia, neurologic pain or weakness, headaches, seizures, cervical chain adenopathy, constitutional symptoms, depression, delirium, history of heavy alcohol consumption, hepatomegaly, and hemoptysis.

• #72 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Results of blood tests and stains of the cancer cells for alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) are often positive in germ cell tumors. […] Its important to identify germ cell tumors because they often respond well to certain combinations of chemotherapy drugs with good outcomes and sometimes, cures. […] Treatment of melanoma depends on whether it has spread only to lymph nodes or whether internal organs are also involved. […] The main goal in trying to determine the source of a CUP is to see if you have a cancer that may respond well to specific treatments. […] Tests of the cancer cells for thyroglobulin can identify many thyroid cancers, which are often effectively treated with radioactive iodine injections. […] A type of poorly differentiated malignant neoplasm called small cell carcinoma or poorly differentiated neuroendocrine carcinoma can develop in the lungs and, less often, in other organs.

• #73 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Because CUP refers to many different cancers, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. […] If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. […] Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. […] Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

• #74 Carcinomas of an unknown primary origin—diagnosis and treatment | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2011.158

  Carcinomas of an unknown primary origin (CUP) account for 35% of all malignancies and are thus among the ten most-frequent cancers worldwide. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost’ CUP origins. In the future, genome-wide screening may change the management of patients with CUP. […] Medical oncologists should use validated prognostic scores to define the treatment strategy; for example, the French prognostic score based on performance score and lactate dehydrogenase levels.

• #75 Carcinomas of an unknown primary origin—diagnosis and treatment | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2011.158

  15% of carcinomas of an unknown primary origin (CUP) have an identifiable subcategory, including adenocarcinoma in axillary lymph nodes, peritoneal papillary serous carcinoma, squamous carcinoma involving cervical lymph nodes, and poorly differentiated neuroendocrine CUP. […] The remaining 85% of patients that do not fit into these specific subgroups require empiric chemotherapy, which usually consists of cisplatin-based dual chemotherapy.

• #76 Cancer of Unknown Primary: Diagnosis and Treatment

  https://www.ekjm.org/journal/view.php?number=25767

  Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. […] It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. […] Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of 1 year. […] Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking.

• #77 Cancer of Unknown Primary: Diagnosis and Treatment

  https://www.ekjm.org/journal/view.php?number=25767

  Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. […] It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. […] Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of 1 year. […] Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking.

• #78 Carcinoma of Unknown Primary Treatment – NCI

  https://www.cancer.gov/types/unknown-primary/patient/unknown-primary-treatment-pdq

  The following tests and procedures may be done to find where the cancer first began: CT scan (CAT scan), MRI (magnetic resonance imaging), PET scan (positron emission tomography scan), Mammogram, Endoscopy, Tumor marker test. […] Sometimes, none of the tests can find the primary cancer site. In these cases, treatment may be based on what the doctor thinks is the most likely type of cancer. […] The prognosis depends on the following: Where the cancer began in the body and where it has spread, The number of organs with cancer in them, The way the tumor cells look when viewed under a microscope, Whether the patient is male or female, Whether the cancer has just been diagnosed or has recurred (come back). […] There are different types of treatment for patients with carcinoma of unknown primary (CUP).

• #79 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Because CUP refers to many different cancers, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. […] If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. […] Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. […] Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

• #80 Carcinomas of an unknown primary origin—diagnosis and treatment | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2011.158

  Carcinomas of an unknown primary origin (CUP) account for 35% of all malignancies and are thus among the ten most-frequent cancers worldwide. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost’ CUP origins. In the future, genome-wide screening may change the management of patients with CUP. […] Medical oncologists should use validated prognostic scores to define the treatment strategy; for example, the French prognostic score based on performance score and lactate dehydrogenase levels.

• #81 Cancer of Unknown Primary Site (CUPS) | Mays Cancer Center

  https://cancer.uthscsa.edu/cancer-care/types-and-treatments/cancer-unknown-primary-site-cups

  Cancers of unknown primary site (CUPS) can be challenging to treat. The doctors at Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center, have specialized expertise to treat these complex conditions precisely. […] Cancer of unknown primary site (CUPS) is what doctors call a cancer when diagnostic tests cannot determine where the cancer started. You may also hear the term occult primary cancer. Our team includes specialists who understand how to diagnose and treat these complex conditions. […] Our cancer doctors use a wide range of diagnostic tools to learn as much as we can about a cancer. These tests help us recommend treatments that are appropriate for you. […] All CUPS diagnoses at Mays Cancer Center are reviewed by at least two pathologists. Our team includes pathology doctors who have substantial experience evaluating these uncommon cancers.

• #82 Cancer of Unknown Primary Diagnosis | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/cancer-unknown-primary-origin/cancer-unknown-primary-diagnosis

  For cancers of unknown primary, doctors at Memorial Sloan Kettering use a combination of sophisticated tests to determine the type of cancer and to prepare treatment plans. Treatment is managed by a team of doctors. We work together to ensure that every individual receives personalized care. […] First, the tumor tissue from a biopsy or surgery is reviewed by an MSK pathologist. Next, a doctor will review the studies that have already been performed on the individual. Care teams may recommend additional tests to help identify the primary site of disease. […] For many people, however, the primary site cannot be found. In these cases, the diagnosis focuses on identifying the location of the cancer and the type of cells that make up the tumor to develop a care plan. […] For most people with cancer of unknown primary, doctors rely on information from blood tests, imaging studies, molecular analysis, and pathology tests to learn more about a tumor.

• #83 Metastatic Cancer With Unknown Primary Site: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2006637-overview

  In metastatic cancer, the primary site of the cancer usually dictates the treatment, expected outcome, and overall prognosis. Consequently, in patients who present with metastatic cancer without a known primary site, the search for the primary site has high priority. This search is best conducted by a multidisciplinary team, consisting at a minimum of clinicians, radiologist, internist, radiation oncologist, and pathologist for resolving the most challenging cases. Molecular profiling is essential for all patients, as discovery of a targetable mutation can sometimes dramatically alter the patient’s prognosis. […] Examination of an additional tissue sample very often proves helpful in this diagnostic process, and is often done if the initial biopsy result is equivocal. Special stains and genomic and proteomic testing can be done with a clear plan of action. If those do not yield a diagnosis, the pattern of organ system involvement and the cytologic diagnosis may help in identifying the primary site. Clinical reassessment of the patient, including close questioning about signs and symptoms, may bring to light previously unreported issues that may help guide diagnosis.

• #84 Cancer of Unknown Primary Site (CUPS) | Mays Cancer Center

  https://cancer.uthscsa.edu/cancer-care/types-and-treatments/cancer-unknown-primary-site-cups

  Cancers of unknown primary site (CUPS) can be challenging to treat. The doctors at Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center, have specialized expertise to treat these complex conditions precisely. […] Cancer of unknown primary site (CUPS) is what doctors call a cancer when diagnostic tests cannot determine where the cancer started. You may also hear the term occult primary cancer. Our team includes specialists who understand how to diagnose and treat these complex conditions. […] Our cancer doctors use a wide range of diagnostic tools to learn as much as we can about a cancer. These tests help us recommend treatments that are appropriate for you. […] All CUPS diagnoses at Mays Cancer Center are reviewed by at least two pathologists. Our team includes pathology doctors who have substantial experience evaluating these uncommon cancers.

• #85 Cancer of Unknown Primary Diagnosis | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/cancer-unknown-primary-origin/cancer-unknown-primary-diagnosis

  For cancers of unknown primary, doctors at Memorial Sloan Kettering use a combination of sophisticated tests to determine the type of cancer and to prepare treatment plans. Treatment is managed by a team of doctors. We work together to ensure that every individual receives personalized care. […] First, the tumor tissue from a biopsy or surgery is reviewed by an MSK pathologist. Next, a doctor will review the studies that have already been performed on the individual. Care teams may recommend additional tests to help identify the primary site of disease. […] For many people, however, the primary site cannot be found. In these cases, the diagnosis focuses on identifying the location of the cancer and the type of cells that make up the tumor to develop a care plan. […] For most people with cancer of unknown primary, doctors rely on information from blood tests, imaging studies, molecular analysis, and pathology tests to learn more about a tumor.

• #86 Cancer of Unknown Primary Diagnosis | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/cancer-unknown-primary-origin/cancer-unknown-primary-diagnosis

  Many people with a tumor designated as cancer of unknown primary have already had some of these tests when they come to MSK. Our doctors may do additional laboratory and imaging tests to narrow down the possible organs or parts of the body where the cancer began. Tests may also be needed to identify the kinds of cells in the tumors. With these results, our doctors can recommend the most-effective treatment possible. […] A biopsy (removal of tumor tissue or fluid for examination under a microscope) is commonly performed to confirm a diagnosis of cancer of unknown primary and to obtain cells for further study under a microscope. A pathologist examines the sample to determine the type of cells involved. […] In many cases, routine laboratory tests do not provide enough information about a cancer of unknown primary to identify or narrow down the possible primary site. Memorial Sloan Ketterings pathologists are highly experienced in identifying subtle cell patterns that may indicate certain types of cancer.

• #87 Carcinoma of Unknown Primary | Oncohema Key

  https://oncohemakey.com/carcinoma-of-unknown-primary/

  In the past, minimalist diagnostic strategies had been advocated, limiting the scope of initial evaluations to differentiate only between treatable and untreatable disease. Others have supported a more aggressive approach, wherein a complete assessment of the extent of the disease and detection of the primary tumor site are attempted. An important determinant of the appropriate extent of evaluation for any patient with CUP is whether the data obtained by a diagnostic test will influence treatment decisions. If a treatable or potentially curable cancer is strongly suspected, further investigation should proceed until a precise clinical diagnosis can be made, provided that therapy is not unreasonably delayed. The recommended general approach at the present time is thus one of a directed evaluation based on clinical presentation and pathologic findings; predictions of tumor origin or mutations from molecular profiling techniques may also play a role in streamlining the scope of evaluation.

• #88 Carcinoma of Unknown Primary | Oncohema Key

  https://oncohemakey.com/carcinoma-of-unknown-primary/

  In the absence of contraindications, a baseline intravenous contrast CT scan of the chest, abdomen, and pelvis is the standard of care, as supported by the National Comprehensive Cancer Network and National Institute for Health and Clinical Excellence CUP radiology guidelines. Patients with CUP should then be approached in a directed fashion. All pathologic material obtained at biopsy from a patient with CUP should be evaluated by an experienced pathologist who is familiar with CUP workup. The pathologist should also be informed of the patients pertinent history and clinical findings so that he or she can recommend further analysis on the basis of this information. In the CUP world, pathology trumps radiology. Collaboration between the pathologist and treating oncologist is critical. Adequate tissue sampling is essential.

• #89 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  The diagnostic utility of positron emission tomography (PET) is poorly defined; it is beneficial in selected patients. […] The role of tissue of origin molecular profiling assays continues to evolve; these tests are beneficial in selected patients. […] The management of CUP has been evolving, and recently developed sophisticated diagnostic modalities and novel therapies present both an opportunity and a challenge. […] The inability to identify a primary carcinoma also generates anxiety for the patient, who may feel that the physicians evaluation has been inadequate or that the prognosis would be improved if a primary site could be established. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival and provide a reasonable probability of locating the primary anatomic site without compromising the quality of life with difficult and time-consuming diagnostic studies.

• #90 Unknown Primary Carcinomas: Diagnosis and Management

  https://www.cancernetwork.com/view/unknown-primary-carcinomas-diagnosis-and-management

  The treatment of malignancy is traditionally based on the identification of the origin of the tumor, and treatment is chosen and initiated based upon the natural history and the most specific therapies available for a certain type of tumor. Without knowledge of the primary site, the oncologist is often hesitant to recommend therapy. […] An important determinant of the appropriate extent of evaluation for a given patient with an unknown primary carcinoma is whether the data obtained by a diagnostic test will influence treatment decisions. If the initial data point to a treatable or potentially curable cancer (eg, a germ-cell tumor or lymphoma), then further investigation should proceed until a precise clinical diagnosis can be made. Clinical data support the belief that patients who have unknown primary tumors that are later proved to have originated from a given site or from unique histology have an overall prognosis similar to that of patients who present with a known primary tumor.

• #91 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  A cancer of unknown primary (CUP) is defined as a biopsy-confirmed malignancy with no established primary site after pathological evaluation and radiographic studies. […] The pathologist has a central role in the evaluation of CUP. A thorough evaluation of an adequate specimen for histological, immunohistochemical, molecular diagnostics, next-generation sequencing (NGS), and, when appropriate, electron microscopic evaluations provides the most important clues in the diagnosis of CUP. […] The following tests may be used to diagnose CUP: Gene expression profiling and NGS may identify a potential site of origin in patients with CUP. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile.

• #92 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  The U.S. Food and Drug Administration (FDA) has approved some novel targeted therapies when a molecular target is identified in a cancer, regardless of primary site (including when no primary site is evident with metastases). […] A meta-analysis of five studies including 1,114 patients compared site-specific therapy from genomic profiling versus empiric therapy. […] In a retrospective analysis, a cohort of 97 patients with CUP underwent NGS of tissue- or blood-derived cell-free DNA. […] The median number of pathogenic genomic alterations found in tissue was four (range, 0-25), and the median number of genomic alterations found in cfDNA was two (range, 0-9). […] The presence of elevated serum or tissue levels of AFP and/or beta-hCG suggests testicular cancer or extragonadal germ cell tumor in males.

• #93 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  The NCCN lists two primary applications of molecular profiling in management of CUP; using gene expression profiling and molecular cancer classifier assays to determine tissue of origin for site-specific therapy, and identifying actionable mutations for targeted therapy (NCCN, 2024). […] The 2023 NCCN guidelines for the workup of an occult primary malignancy address the use of molecular methods in the classification of tumors. The guidelines state Gene sequencing to predict tissue of origin is not recommended. […] Overall, the NCCN states that the clinical benefit of using molecular profiling to guide treatment decisions in CUP remains to be determined. […] A 2010 clinical guideline from NICE, which was reaffirmed in 2017, recommended against the use of gene expression-based profiling to identify primary tumors in patients with provisional CUPs.

• #94 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  The NCCN lists two primary applications of molecular profiling in management of CUP; using gene expression profiling and molecular cancer classifier assays to determine tissue of origin for site-specific therapy, and identifying actionable mutations for targeted therapy (NCCN, 2024). […] The 2023 NCCN guidelines for the workup of an occult primary malignancy address the use of molecular methods in the classification of tumors. The guidelines state Gene sequencing to predict tissue of origin is not recommended. […] Overall, the NCCN states that the clinical benefit of using molecular profiling to guide treatment decisions in CUP remains to be determined. […] A 2010 clinical guideline from NICE, which was reaffirmed in 2017, recommended against the use of gene expression-based profiling to identify primary tumors in patients with provisional CUPs.

• #95 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  In 2023, EMSO updated their clinical practice guidelines for the diagnosis, treatment, and follow-up of cancer of unknown primary. The guideline states that The clinical utility of gene expression profiling to help elucidate the likely primary is not currently supported by high-level evidence. […] The NCI acknowledges the possible utility of gene expression profiling and next generation sequencing to identify a potential site of origin in patients with CUP (NCI, 2023). […] The American Cancer Society acknowledges the possible use of gene expression profiling and molecule genetic testing for the diagnosis of cancers of unknown primary. However, they note that molecular genetic testing is not needed in most cases, but its sometimes helpful in classifying some cancers when other tests have not provided clues regarding their origin.

• #96 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. Identifying patients with prognostically favorable disease is important, since they may derive substantial benefit, including prolonged survival, from directed treatment. In CUP cases, a focused search for the primary tumor is recommended. […] The criteria for CUP include a biopsy-proven malignancy for which the anatomic origin is unknown after a medical history has been obtained, a detailed physical examination has been performed, and liver and kidney function tests, blood tests, chest radiography, abdomen and pelvis computed tomography (CT), and mammography or a prostate-specific antigen (PSA) test have been performed.

• #97 Carcinoma of Unknown Primary – Clinical Tree

  https://clinicalpub.com/carcinoma-of-unknown-primary/

  We define patients with CUP as having a biopsy-proven malignancy for which the anatomic origin remains unidentified after history and physical examination, laboratory studies including liver and renal function tests, hemogram, computed tomography (CT) of the chest, abdomen, and pelvis; and mammography in women and measurement of prostate-specific antigen (PSA) in men based on presentation. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival based on extent of disease and performance status without compromising quality of life with difficult and time-consuming diagnostic studies. […] An accurate pathologic assessment of biopsy material is essential in the initial evaluation of the patient with suspected CUP; core biopsy is preferred over a fine-needle aspirate specimen.

• #98 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  The pathologist has an indispensable role in the evaluation of cancer of unknown primary origin. […] Patients with cancer of unknown primary origin are presumed to all have stage IV disease at the time of initial presentation. […] Guidelines from the European Society for Medical Oncology (ESMO) recommend selected marker assays as part of the basic immunohistochemical workup of cancers of unknown primary.

• #99 Carcinoma of Unknown Primary Origin

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2631214/

  Carcinoma of unknown primary origin (CUP) is a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. Identifying patients with prognostically favorable disease is important, since they may derive substantial benefit, including prolonged survival, from directed treatment. In CUP cases, a focused search for the primary tumor is recommended. […] The criteria for CUP include a biopsy-proven malignancy for which the anatomic origin is unknown after a medical history has been obtained, a detailed physical examination has been performed, and liver and kidney function tests, blood tests, chest radiography, abdomen and pelvis computed tomography (CT), and mammography or a prostate-specific antigen (PSA) test have been performed.

• #100 Metastatic Cancer With Unknown Primary Site Workup: Approach Considerations, Laboratory Studies, Imaging Studies

  https://emedicine.medscape.com/article/280505-workup

  A minimal basic workup for cancer of unknown primary origin comprises basic blood and biochemical analyses along with computed tomography (CT) scans of the abdomen and pelvis. […] When these investigations fail to reveal a potential primary lesion, a cancer of unknown primary origin is assumed. The goal of initial evaluation should be to detect the small subset of patients who warrant potentially curative management. […] Lab studies for metastatic cancer with an unknown primary site should include the following: Complete blood cell count (iron deficiency anemia may point toward an occult gastrointestinal malignancy leading to chronic blood loss). […] Imaging studies should include the following: Chest radiograph, Computed tomography (CT) of abdomen and pelvis, Mammography in women. […] The role of tumor markers, such as alpha-fetoprotein (AFP), betahuman chorionic gonadotropin (beta-HCG), cancer antigen 125 (CA125), CA 27.29, CA 19.9, and carcinoembryonic antigen (CEA), to establish a specific primary site or to identify patients who respond to chemotherapy remains unclear and should probably be limited to cases in which a particular primary site is favored.

• #101 Carcinoma of Unknown Primary – Clinical Tree

  https://clinicalpub.com/carcinoma-of-unknown-primary/

  We define patients with CUP as having a biopsy-proven malignancy for which the anatomic origin remains unidentified after history and physical examination, laboratory studies including liver and renal function tests, hemogram, computed tomography (CT) of the chest, abdomen, and pelvis; and mammography in women and measurement of prostate-specific antigen (PSA) in men based on presentation. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival based on extent of disease and performance status without compromising quality of life with difficult and time-consuming diagnostic studies. […] An accurate pathologic assessment of biopsy material is essential in the initial evaluation of the patient with suspected CUP; core biopsy is preferred over a fine-needle aspirate specimen.

• #102 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  An accurate pathological assessment of biopsy material is essential in the initial evaluation of the patient with suspected CUP. […] The initial pathological assessment of the biopsy specimen is by light microscopic examination of paraffin sections stained with hematoxylin and eosin. […] Immunohistochemical markers play a significant role in the diagnosis and workup of CUP. […] The potential role of serum tumor markers in the evaluation and management of patients with CUP has been reviewed. […] The laboratory evaluation of patients with suspected CUP should begin with a complete blood count to screen for anemia. […] Bilateral mammography should be a part of the routine evaluation of most women with CUP. […] Computed tomography (CT) of the abdomen and pelvis is routinely performed as part of the diagnostic evaluation of CUP to locate the primary tumor, to evaluate the extent of disease, and to select the most favorable biopsy site.

• #103 Carcinoma of Unknown Primary | Oncohema Key

  https://oncohemakey.com/carcinoma-of-unknown-primary/

  In the absence of contraindications, a baseline intravenous contrast CT scan of the chest, abdomen, and pelvis is the standard of care, as supported by the National Comprehensive Cancer Network and National Institute for Health and Clinical Excellence CUP radiology guidelines. Patients with CUP should then be approached in a directed fashion. All pathologic material obtained at biopsy from a patient with CUP should be evaluated by an experienced pathologist who is familiar with CUP workup. The pathologist should also be informed of the patients pertinent history and clinical findings so that he or she can recommend further analysis on the basis of this information. In the CUP world, pathology trumps radiology. Collaboration between the pathologist and treating oncologist is critical. Adequate tissue sampling is essential.

• #104 Testing for a Cancer of Unknown Primary by Location | American Cancer Society

  https://www.cancer.org/cancer/types/cancer-unknown-primary/detection-diagnosis-staging/testing-approach.html

  Based on the classification and the location of the metastatic cancer of unknown primary, doctors decide which additional tests should be done. […] The classification and location also help the doctor decide what other imaging tests may be helpful in looking for the primary site. […] Tests will be done to look at these areas thoroughly for signs of where the cancer may have started. […] Imaging tests like CT or MRI scans of the sinuses and neck area may be used to look for small cancers that may have already spread to lymph nodes in the neck. […] If a breast cancer diagnosis cannot be confirmed, tests to look for lung cancer may be done. […] Tests for CA-125 in the blood and tumor samples are positive in most ovarian and fallopian tube cancers, and can be used to help determine whether the primary tumor is likely to be from there or some other organ.

• #105 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  A cancer of unknown primary (CUP) is defined as a biopsy-confirmed malignancy with no established primary site after pathological evaluation and radiographic studies. […] The pathologist has a central role in the evaluation of CUP. A thorough evaluation of an adequate specimen for histological, immunohistochemical, molecular diagnostics, next-generation sequencing (NGS), and, when appropriate, electron microscopic evaluations provides the most important clues in the diagnosis of CUP. […] The following tests may be used to diagnose CUP: Gene expression profiling and NGS may identify a potential site of origin in patients with CUP. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile.

• #106 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  The U.S. Food and Drug Administration (FDA) has approved some novel targeted therapies when a molecular target is identified in a cancer, regardless of primary site (including when no primary site is evident with metastases). […] A meta-analysis of five studies including 1,114 patients compared site-specific therapy from genomic profiling versus empiric therapy. […] In a retrospective analysis, a cohort of 97 patients with CUP underwent NGS of tissue- or blood-derived cell-free DNA. […] The median number of pathogenic genomic alterations found in tissue was four (range, 0-25), and the median number of genomic alterations found in cfDNA was two (range, 0-9). […] The presence of elevated serum or tissue levels of AFP and/or beta-hCG suggests testicular cancer or extragonadal germ cell tumor in males.

• #107 Diagnosis of cancer of unknown primary | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/cancer-of-unknown-primary/diagnosis

  Understanding how cancer spreads also helps the healthcare team find out where CUP started. Some types of cancer spread in a predictable way from one part of the body to another. So the healthcare team will check if the CUP is a type of cancer that they know usually spreads to the organ or tissue where the CUP was found. Sometimes the symptoms that CUP causes can also help doctors decide where to look for the primary site. […] In most cases, doctors can eventually find the primary site. Once they identify the primary site, the cancer is treated like the type of cancer that was found. […] Sometimes doctors cant identify the primary site. This may be because the original tumour is very small and hard to find. In some cases, the bodys immune system may have destroyed the original tumour after the cancer spread. In these cases, a person is diagnosed with CUP.

• #108 Carcinoma of unknown primary | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/carcinoma-unknown-primary

  If a biopsy finds cells that spread from somewhere else, your healthcare team works to find where they started. The place where a cancer started growing is called the primary cancer. […] Sometimes these tests can find the primary cancer. If this happens, you no longer have carcinoma of unknown primary. For some people, the primary cancer is never found. If this happens, your healthcare team will use information from all of your tests to make a treatment plan.

• #109 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  The diagnostic utility of positron emission tomography (PET) is poorly defined; it is beneficial in selected patients. […] The role of tissue of origin molecular profiling assays continues to evolve; these tests are beneficial in selected patients. […] The management of CUP has been evolving, and recently developed sophisticated diagnostic modalities and novel therapies present both an opportunity and a challenge. […] The inability to identify a primary carcinoma also generates anxiety for the patient, who may feel that the physicians evaluation has been inadequate or that the prognosis would be improved if a primary site could be established. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival and provide a reasonable probability of locating the primary anatomic site without compromising the quality of life with difficult and time-consuming diagnostic studies.

• #110 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Patients with cancer of unknown primary site suffer the burden of an uncertain disease, which is characterized by the impossibility to identify the tissue where the tumor has originated. The identification of the primary site of a tumor is of great importance for the patient to have access to site-specific treatments and be enrolled in clinical trials. Therefore, patients with cancer of unknown primary have reduced therapeutic opportunities and poor prognosis. […] A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). […] When dealing with a potential CUP diagnosis, clinical practice guidelines suggest a thorough diagnostic workup, which includes routine clinical evaluation, extensive physical examination, blood/biochemical analyses, and radiological tests.

• #111 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  Positron emission tomography with 18fluoro-2-deoxy-d-glucose (18F-FDG-PET) is a noninvasive nuclear imaging technique that has been proven to be a valuable diagnostic tool in identifying primary malignant tumors and the extent of metastatic disease. […] The premise for studying the role of molecular profiling in CUP cancers is that metastatic tumors have molecular signatures that match their tissue of origin. […] The MD Anderson Cancer Center, in collaboration with our colleagues at Sarah Cannon Cancer Center, reported the first large CUP series that evaluated the feasibility of a 10-gene RT-PCR assay to identify the ToO in CUP patients. […] There are several challenges in the field of molecular profiling and CUP. […] Given the heterogeneity of the CUP cancers, it is difficult to interpret clinical trials and definite benefit of any particular combination in CUP cancers.

• #112 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  If this initial series of diagnostic tests is still insufficient to identify the site of the primary tumor, additional specific tests can be considered. […] Finally, the last and most critical step is represented by immunohistochemical testing, which remains the most important diagnostic tool in establishing the tissue of origin. If, after these attempts, the primary tumor remains elusive, a diagnosis of CUP is confirmed. […] The first IHC testing is made to exclude tumor types with specific treatment requirements, such as lymphoma, melanoma, germ-cell tumors, or sarcoma. […] Despite the existence of specific practice guidelines for CUP IHC testing and the definition of diagnostic algorithms to identify the tissue of origin, small pieces of biopsy tissue limit this diagnostic workup.

• #113 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  If this initial series of diagnostic tests is still insufficient to identify the site of the primary tumor, additional specific tests can be considered. […] Finally, the last and most critical step is represented by immunohistochemical testing, which remains the most important diagnostic tool in establishing the tissue of origin. If, after these attempts, the primary tumor remains elusive, a diagnosis of CUP is confirmed. […] The first IHC testing is made to exclude tumor types with specific treatment requirements, such as lymphoma, melanoma, germ-cell tumors, or sarcoma. […] Despite the existence of specific practice guidelines for CUP IHC testing and the definition of diagnostic algorithms to identify the tissue of origin, small pieces of biopsy tissue limit this diagnostic workup.

• #114 Metastatic Cancer With Unknown Primary Site: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2006637-overview

  Despite the increasing sophistication in the diagnostic workup for malignancies, detailed investigations fail to reveal a primary site of origin in a minority of patients with metastatic cancer. This is often referred to as carcinoma of unknown primary origin (CUP) or occult primary malignancy. […] The diagnosis of CUP thus generates anxiety among patients and caregivers, who may feel that the evaluation has been incomplete. […] Nevertheless, a precise pathologic diagnosis with next-generation sequencing may identify targetable mutations and help guide therapy. […] CUP is characterized by an aggressive course and resistance to conventional chemotherapy.

• #115 Cancer of unknown primary origin – Wikipedia

  https://en.wikipedia.org/wiki/Cancer_of_unknown_primary_origin

  Because CUP refers to many different cancers, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. […] If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. […] Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. […] Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

• #116 All About Cancer of Unknown Primary | OncoLink

  https://www.oncolink.org/cancers/carcinoma-of-unknown-primary/all-about-cancer-of-unknown-primary

  Your provider will ask you questions about your health history and will do a physical exam. You may need lab tests and imaging. Blood tests may look at how your organs are working and also look for certain tumor markers. Imaging tests may include x-rays, CTs, MRIs, PET scans, procedures done with scopes, and ultrasounds. You may also have a biopsy to look at the cells and to see what type they are. Your provider will talk to you about what tests you will need to have done. […] There is no standard staging used for cancer of unknown primary. […] Treatment for CUP depends on many factors, like your cancer stage, age, overall health, and testing results, especially the results of your biopsy. Your treatment may include some or all of the following: Surgery. Chemotherapy. Radiation Therapy. Hormone Therapy. Other Medications and Treatments. Clinical Trials.

• #117 All About Cancer of Unknown Primary | OncoLink

  https://www.oncolink.org/cancers/carcinoma-of-unknown-primary/all-about-cancer-of-unknown-primary

  Surgery is used to remove as much of the cancer as possible, called a resection. Surgery may also be done to remove lymph nodes affected by the cancer. You may receive chemotherapy or radiation therapy before or after surgery. Talk with your provider about your treatment options, including whether surgery is part of your plan. […] Chemotherapy is the use of anti-cancer medicines that go through your whole body to kill cancer cells. These medicines may be given through a vein (IV, intravenously) or by mouth. Chemotherapy is used often for CUP because it can attack cancer cells in many parts of your body. […] Your quality of life is very important and sometimes treatment like chemotherapy, radiation, surgery, and other treatments can be used to lessen symptoms or side effects that you may have. Treatments used to help you live a better life, rather than cure your cancer, are called palliative treatment. Palliative treatment can be used to manage pain, nutrition issues, and other side effects.

• #118 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #119 Cancer of Unknown Primary Diagnosis | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/cancer-of-unknown-primary/cancer-of-unknown-primary-diagnosis.html

  With new scientific advances, doctors increasingly are able to find where cancer of unknown primary (CUP) began. In fact, now the primary site can be found in about four of five cases that originally were diagnosed as CUP. […] The first step in diagnosing CUP is a thorough history and physical examination. The doctor will ask you questions about your current and past health and risk factors, such as smoking or family history. […] If your doctor suspects cancer of unknown primary, one or more of the following tests may be done: […] Different methods are used to perform biopsies for CUP, depending on where the cancer is and the type of cancer. […] Staging is a way of determining how much disease is in the body and where it has spread. This information is important because it determines the type of treatment you will receive and the outlook for your recovery (prognosis). […] Cancer of unknown primary cannot be staged the way other cancers are because the origin of the primary cancer is not known. But doctors can make some predictions based on: […] MD Anderson patients have access to clinical trials offering promising new treatments that cannot be found anywhere else.

• #120 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #121 Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling – PubMed

  https://pubmed.ncbi.nlm.nih.gov/22987975/

  Carcinoma of unknown primary (CUP) remains a common and challenging clinical problem. The aim of diagnostic work-up in CUP is to classify as specifically as possible the cancer affecting the patient, according to the broad tumour type, subtype and, where possible, site of origin. This classification currently best predicts patient outcome and guides optimal treatment. a stepwise approach to diagnostic work-up is described. although pathology is based on morphology, the assessment of tissue-specific genes through immunohistochemistry (IHC) substantially helps tumour classification at each diagnostic step. […] For IHC in CUP, recent improvements include more standardised approaches and marker panels plus new markers. Tissue-specific genes are also being used in CUP work-up through molecular profiling. Large-scale profiles of hundreds of tumours of different types have been generated, compared and used to generate diagnostic algorithms. Commercial tests for CUP classification have been developed at the mRNa and microRNA and (miRNA) levels and validated in metastatic tumours and CUPs. While currently optimal pathology and IHC remain the 'gold standard’ for CUP diagnostic work-up, and full clinical correlation is vital, the molecular tests appear to perform well: in the main diagnostic challenge of undifferentiated or poorly differentiated tumours, molecular profiling performs as well as or better than IHC.

• #122 Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11563-1

  Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. […] The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). […] Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. […] Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. […] P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas.

• #123 Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11563-1

  We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. […] The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. […] Molecular testing is also predictive of survival rates. […] Identification of the primary tumor site is pivotal for the treatment and prognosis of patients with CUP. […] Various panels of IHC markers have been employed on the basis of morphological findings for the identification of the CUP primary sites, particularly in poorly differentiated or undifferentiated tumors. […] However, previous studies have revealed accurate identification by IHC analysis in only 5065% of metastatic cancers. […] Our results demonstrated no diagnostic value of IHC testing in the identification of primary tumors in approximately half of all patients.

• #124 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #125 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  Cancers of unknown primary (CUP) origin account for 3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. […] Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. […] With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. […] Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. […] The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

• #126 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #127 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #128 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Our study proved that site-specific therapy contributed to a significantly longer median PFS compared to empirical chemotherapy (9.6 months vs. 6.6 months; p=0.017). […] This significant breakthrough not only opens a new chapter for the clinical management of CUP, but also establishes site-specific first-line treatment as a cornerstone in improving patient prognosis for cancer of unknown primary. […] These results demonstrate that second-line PD-1 blockade in combination with bevacizumab and nab-paclitaxel is an effective and well-tolerated treatment regimen for patients with CUP. […] In clinical practice, routine examinations for patients with cancer of unknown primary (CUP) include taking a medical history, conducting a physical examination, and detecting serum tumor markers. […] IHC or MTP-based methodologies were suggested to assist in identifying the tissue origin of CUP and guiding site-specific therapy for CUP.

• #129 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Our study proved that site-specific therapy contributed to a significantly longer median PFS compared to empirical chemotherapy (9.6 months vs. 6.6 months; p=0.017). […] This significant breakthrough not only opens a new chapter for the clinical management of CUP, but also establishes site-specific first-line treatment as a cornerstone in improving patient prognosis for cancer of unknown primary. […] These results demonstrate that second-line PD-1 blockade in combination with bevacizumab and nab-paclitaxel is an effective and well-tolerated treatment regimen for patients with CUP. […] In clinical practice, routine examinations for patients with cancer of unknown primary (CUP) include taking a medical history, conducting a physical examination, and detecting serum tumor markers. […] IHC or MTP-based methodologies were suggested to assist in identifying the tissue origin of CUP and guiding site-specific therapy for CUP.

• #130 Carcinoma of Unknown Primary: Diagnostics and the Potential of Transoral Surgery | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_12

  To improve the identification ratio in CUP, TBM has gained popularity in the diagnostic work up. […] Although there is sufficient proof for the added value of TBM, the question remains as to when and how to perform TBM. […] Identification of a primary lesion leads to appropriate staging and understanding of the disease. This is of importance for both the patient and the treating physician. […] In case the primary tumour is identified after thorough work up, the tumour should be staged and treated accordingly. […] The use of TBM (and PTE) in HPV-negative CUP is questionable since the detection rate in this category has proven to be very low.

• #131 Cancer of unknown primary site

  https://www.racgp.org.au/afp/2015/september/cancer-of-unknown-primary-site

  Published CUP clinical practice guidelines recommend diagnostic pathways that vary depending on the extent of metastasis, the involved site(s), the suspected origin and the overall health of the patient. […] For patients who undergo tumour biopsy or excision, immunohistochemistry can help to identify the subset with a favourable prognosis and guide treatment on the basis of the suspected tumour type. […] A pragmatic approach is usually taken, which involves targeted diagnostic investigations and treatment of treatable malignancies. […] The high rates of emergency department visits before and after diagnosis suggest gaps in care, or may simply reflect the need for urgent attention given the aggressive nature of CUP. […] Although most patients with CUP have poor prognoses, a recognised subset has a favourable prognosis and must be offered treatment according to published guidelines.

• #132 Cancer of Unknown Primary Diagnostics Are Advancing | Clinical Lab Products

  https://clpmag.com/disease-states/cancer/unknown-other-cancer/cancer-of-unknown-primary-diagnostics-are-advancing/

  Cancer of Unknown Primary Diagnostics Are Advancing […] Despite limited progress in prognosis over decades, recent advancements in molecular diagnostics and site-specific therapies are transforming the clinical management of cancer of unknown primary (CUP). […] CUP remains a major cause of cancer-related death due to its elusive primary origin and poor prognosis despite traditional chemotherapy. […] Modern molecular techniques have drastically improved CUP diagnostic accuracy, enabling tailored treatments. […] Advancements in the current era of molecular diagnostics, based on cytology, histology, gene expression profiling (GEP), and genomic and epigenomic analysis have greatly improved the diagnostic accuracy of cancer of unknown primary, surpassing 90%. […] Advancements in the diagnosis of CUP have laid a solid foundation for the application of site-specific therapies, ultimately improving patient outcomes for those affected by this condition.

• #133 Cancer of Unknown Primary Site (CUPS) | Mays Cancer Center

  https://cancer.uthscsa.edu/cancer-care/types-and-treatments/cancer-unknown-primary-site-cups

  Our specialists may recommend any combination of tests in an effort to identify where the cancer originated. Tests can also give doctors important details about a cancers makeup (genetic and molecular details). This information helps guide your personalized treatment recommendations. […] We may recommend imaging tests, such as X-rays, CT, PET or MRI scans, use different technologies to show abnormal growths (tumors) or cancer spread. […] Endoscopic tests use sophisticated tools that are guided through the mouth or nose to examine areas inside the body. Endoscopic tools enable doctors to inspect hard-to-reach areas where cancer can hide, areas that imaging tests wont detect. […] Biopsies analyze a tumor and blood sample in a laboratory. Molecular diagnostic tools can search for more than 600 cancer-causing genes at the same time and help to identify cancer types. Our doctors use the results to determine where the tumor originated from and what treatments could target the specific cancer-causing genes (targets) you have. […] In some cases, our doctors may identify where CUPS developed. If that happens, we refer you to cancer doctors on our team who specialize in treating cancers similar to the one affecting you.

• #134 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  Women with peritoneal carcinomatosis of an undifferentiated adenocarcinoma or serous histology in the absence of an ovarian, fallopian tube, or uterine primary site should undergo diagnostic testing and a therapeutic approach for ovarian cancer. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile. […] Immunological therapy using checkpoint inhibitors such as nivolumab has been given to a general population with unfavorable CUP, resulting in a 22% overall response rate. […] Patients with unfavorable CUP who are not candidates for molecular targeted therapy or immunotherapy are candidates for clinical trials. […] Cytotoxic chemotherapy can be a palliative therapy, but the choice of drugs has been based on a few small clinical studies, with no randomized trials establishing their benefit over best supportive care.

• #135 Metastatic Cancer With Unknown Primary Site: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2006637-overview

  Despite the increasing sophistication in the diagnostic workup for malignancies, detailed investigations fail to reveal a primary site of origin in a minority of patients with metastatic cancer. This is often referred to as carcinoma of unknown primary origin (CUP) or occult primary malignancy. […] The diagnosis of CUP thus generates anxiety among patients and caregivers, who may feel that the evaluation has been incomplete. […] Nevertheless, a precise pathologic diagnosis with next-generation sequencing may identify targetable mutations and help guide therapy. […] CUP is characterized by an aggressive course and resistance to conventional chemotherapy.

• #136 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  The diagnostic utility of positron emission tomography (PET) is poorly defined; it is beneficial in selected patients. […] The role of tissue of origin molecular profiling assays continues to evolve; these tests are beneficial in selected patients. […] The management of CUP has been evolving, and recently developed sophisticated diagnostic modalities and novel therapies present both an opportunity and a challenge. […] The inability to identify a primary carcinoma also generates anxiety for the patient, who may feel that the physicians evaluation has been inadequate or that the prognosis would be improved if a primary site could be established. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival and provide a reasonable probability of locating the primary anatomic site without compromising the quality of life with difficult and time-consuming diagnostic studies.

• #137 All About Cancer of Unknown Primary | OncoLink

  https://www.oncolink.org/cancers/carcinoma-of-unknown-primary/all-about-cancer-of-unknown-primary

  Your provider will ask you questions about your health history and will do a physical exam. You may need lab tests and imaging. Blood tests may look at how your organs are working and also look for certain tumor markers. Imaging tests may include x-rays, CTs, MRIs, PET scans, procedures done with scopes, and ultrasounds. You may also have a biopsy to look at the cells and to see what type they are. Your provider will talk to you about what tests you will need to have done. […] There is no standard staging used for cancer of unknown primary. […] Treatment for CUP depends on many factors, like your cancer stage, age, overall health, and testing results, especially the results of your biopsy. Your treatment may include some or all of the following: Surgery. Chemotherapy. Radiation Therapy. Hormone Therapy. Other Medications and Treatments. Clinical Trials.

• #138 Carcinoma of Unknown Primary | Oncohema Key

  https://oncohemakey.com/carcinoma-of-unknown-primary/

  In the past, minimalist diagnostic strategies had been advocated, limiting the scope of initial evaluations to differentiate only between treatable and untreatable disease. Others have supported a more aggressive approach, wherein a complete assessment of the extent of the disease and detection of the primary tumor site are attempted. An important determinant of the appropriate extent of evaluation for any patient with CUP is whether the data obtained by a diagnostic test will influence treatment decisions. If a treatable or potentially curable cancer is strongly suspected, further investigation should proceed until a precise clinical diagnosis can be made, provided that therapy is not unreasonably delayed. The recommended general approach at the present time is thus one of a directed evaluation based on clinical presentation and pathologic findings; predictions of tumor origin or mutations from molecular profiling techniques may also play a role in streamlining the scope of evaluation.

• #139 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  The diagnostic utility of positron emission tomography (PET) is poorly defined; it is beneficial in selected patients. […] The role of tissue of origin molecular profiling assays continues to evolve; these tests are beneficial in selected patients. […] The management of CUP has been evolving, and recently developed sophisticated diagnostic modalities and novel therapies present both an opportunity and a challenge. […] The inability to identify a primary carcinoma also generates anxiety for the patient, who may feel that the physicians evaluation has been inadequate or that the prognosis would be improved if a primary site could be established. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival and provide a reasonable probability of locating the primary anatomic site without compromising the quality of life with difficult and time-consuming diagnostic studies.

• #140 Carcinoma of Unknown Primary | Clinical Gate

  https://clinicalgate.com/carcinoma-of-unknown-primary-2/

  The diagnostic utility of positron emission tomography (PET) is poorly defined; it is beneficial in selected patients. […] The role of tissue of origin molecular profiling assays continues to evolve; these tests are beneficial in selected patients. […] The management of CUP has been evolving, and recently developed sophisticated diagnostic modalities and novel therapies present both an opportunity and a challenge. […] The inability to identify a primary carcinoma also generates anxiety for the patient, who may feel that the physicians evaluation has been inadequate or that the prognosis would be improved if a primary site could be established. […] An effective diagnostic strategy should take into account the projected natural history and duration of survival and provide a reasonable probability of locating the primary anatomic site without compromising the quality of life with difficult and time-consuming diagnostic studies.

• #141 Carcinomas of an unknown primary origin—diagnosis and treatment | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2011.158

  Carcinomas of an unknown primary origin (CUP) account for 35% of all malignancies and are thus among the ten most-frequent cancers worldwide. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost’ CUP origins. In the future, genome-wide screening may change the management of patients with CUP. […] Medical oncologists should use validated prognostic scores to define the treatment strategy; for example, the French prognostic score based on performance score and lactate dehydrogenase levels.

• #142 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  Cancers of unknown primary (CUP) origin account for 3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. […] Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. […] With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. […] Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. […] The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

• #143 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  Cancers of unknown primary (CUP) origin account for 3% of all cancer diagnoses, whereby the tumor tissue of origin (TOO) cannot be determined. […] Using a uniformly processed dataset encompassing 6756 whole-genome sequenced primary and metastatic tumors, we develop Cancer of Unknown Primary Location Resolver (CUPLR), a random forest TOO classifier that employs 511 features based on simple and complex somatic driver and passenger mutations. […] With CUPLR, we could determine the TOO for 82/141 (58%) of CUP patients. […] Although CUPLR is based on machine learning, it provides a human interpretable graphical report with detailed feature explanations. […] The comprehensive output of CUPLR complements existing histopathological procedures and can enable improved diagnostics for CUP patients.

• #144 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  CUPLR comprises an ensemble of binary random forest classifiers that each discriminate one of 35 cancer types with an overall recall of 90%. […] We find that while RMD and mutational signatures were highly predictive of cancer type, the incorporation of SV features improves prediction performance for cancer types that currently lack highly informative features. […] Furthermore, we have ensured that the output of CUPLR, namely the prediction probabilities and the features supporting each prediction, are humanly interpretable to facilitate diagnostic use and clinical decision-making with CUPLR. […] We thus demonstrate that CUPLR can potentially clarify the TOO for over half of patients with CUP.

• #145 Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features | Nature Communications

  https://www.nature.com/articles/s41467-022-31666-w

  CUPLR comprises an ensemble of binary random forest classifiers that each discriminate one of 35 cancer types with an overall recall of 90%. […] We find that while RMD and mutational signatures were highly predictive of cancer type, the incorporation of SV features improves prediction performance for cancer types that currently lack highly informative features. […] Furthermore, we have ensured that the output of CUPLR, namely the prediction probabilities and the features supporting each prediction, are humanly interpretable to facilitate diagnostic use and clinical decision-making with CUPLR. […] We thus demonstrate that CUPLR can potentially clarify the TOO for over half of patients with CUP.

• #146 Cancer of Unknown Primary: Diagnosis and Treatment

  https://www.ekjm.org/journal/view.php?number=25767

  Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. […] It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. […] Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of 1 year. […] Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking.

• #147 Cancer of Unknown Primary: Diagnosis and Treatment

  https://www.ekjm.org/journal/view.php?number=25767

  Two recent randomized clinical trials failed to show the benefit of TOO-based site-specific therapy over empirical chemotherapy. […] In an era of precision medicine, the use of comprehensive molecular profiling will provide opportunities to identify patient subsets who are susceptible to targeted therapies and immunotherapies.

• #148 Molecular Profiling for Cancers of Unknown Primary Origin

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/molecular-profiling-for-cancers-of-unknown-primary-origin/

  In 2023, EMSO updated their clinical practice guidelines for the diagnosis, treatment, and follow-up of cancer of unknown primary. The guideline states that The clinical utility of gene expression profiling to help elucidate the likely primary is not currently supported by high-level evidence. […] The NCI acknowledges the possible utility of gene expression profiling and next generation sequencing to identify a potential site of origin in patients with CUP (NCI, 2023). […] The American Cancer Society acknowledges the possible use of gene expression profiling and molecule genetic testing for the diagnosis of cancers of unknown primary. However, they note that molecular genetic testing is not needed in most cases, but its sometimes helpful in classifying some cancers when other tests have not provided clues regarding their origin.

• #149 Cancer of Unknown Primary: Challenges and Progress in Clinical Management

  https://www.mdpi.com/2072-6694/13/3/451

  Once the epithelial origin is established, the expression of two keratins, K7 and K20, which broadly define the subsets of carcinoma, is mostly used for CUP primary site predictions. […] International guidelines for tumor treatment are essentially based on primary site definition. With no evidence of a primary site, CUP patients cannot be treated with site-specific therapy; thus, they are managed based on their clinicopathological characteristics. […] An indication of a site of origin in these patients, or an approach based on personalized medicine, may assist the physicians in the selection of the best treatment options, potentially improving CUPs prognosis and survival.

• #150 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  Women with peritoneal carcinomatosis of an undifferentiated adenocarcinoma or serous histology in the absence of an ovarian, fallopian tube, or uterine primary site should undergo diagnostic testing and a therapeutic approach for ovarian cancer. […] Clinical, pathological, and molecular genetic tests have two goals. The first is to identify tumors that are responsive to available therapies. The second is to identify novel targeted therapies that might be applicable to the particular genetic profile. […] Immunological therapy using checkpoint inhibitors such as nivolumab has been given to a general population with unfavorable CUP, resulting in a 22% overall response rate. […] Patients with unfavorable CUP who are not candidates for molecular targeted therapy or immunotherapy are candidates for clinical trials. […] Cytotoxic chemotherapy can be a palliative therapy, but the choice of drugs has been based on a few small clinical studies, with no randomized trials establishing their benefit over best supportive care.

• #151 Cancer of Unknown Primary Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

  The U.S. Food and Drug Administration (FDA) has approved some novel targeted therapies when a molecular target is identified in a cancer, regardless of primary site (including when no primary site is evident with metastases). […] A meta-analysis of five studies including 1,114 patients compared site-specific therapy from genomic profiling versus empiric therapy. […] In a retrospective analysis, a cohort of 97 patients with CUP underwent NGS of tissue- or blood-derived cell-free DNA. […] The median number of pathogenic genomic alterations found in tissue was four (range, 0-25), and the median number of genomic alterations found in cfDNA was two (range, 0-9). […] The presence of elevated serum or tissue levels of AFP and/or beta-hCG suggests testicular cancer or extragonadal germ cell tumor in males.

• #152 Carcinomas of an unknown primary origin—diagnosis and treatment | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/nrclinonc.2011.158

  Carcinomas of an unknown primary origin (CUP) account for 35% of all malignancies and are thus among the ten most-frequent cancers worldwide. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost’ CUP origins. In the future, genome-wide screening may change the management of patients with CUP. […] Medical oncologists should use validated prognostic scores to define the treatment strategy; for example, the French prognostic score based on performance score and lactate dehydrogenase levels.

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