Feochromocytoma – Rokowania, prognozy i postęp choroby

Feochromocytoma
Rokowania, prognozy i postęp choroby

Feochromocytoma to rzadki neuroendokrynny guz nadnerczy, charakteryzujący się potencjałem przerzutowym, co zgodnie z klasyfikacją WHO 2017 dotyczy wszystkich przypadków, niezależnie od obecności przerzutów w chwili diagnozy. Rokowanie jest zróżnicowane, z 5-letnim przeżyciem w przypadku przerzutowego guza wynoszącym od 11,8% do poniżej 50%, natomiast po radykalnym leczeniu chirurgicznym wskaźniki przeżycia 5- i 10-letniego wynoszą odpowiednio 90,8% i 78,7%, a przeżycie wolne od przerzutów po 5 latach to 87,0%. Kluczowe czynniki prognostyczne obejmują wielkość guza (>5,5 cm), poziom wydalania kwasu wanilinomigdałowego (>2,1 mg/dzień/cm), fenotyp wydzielniczy (wysoka noradrenalina, niski stosunek adrenaliny), indeks proliferacji Ki67 (≥10%), lokalizację podprzeponową, funkcjonalność guza, wiek pacjenta, płeć, poziom chromograniny A oraz wyniki badań obrazowych (np. negatywny wychwyt MIBG). Systemy oceny takie jak PASS, GAPP, M-GAPP, COPPs i ASES oferują narzędzia prognostyczne, jednak żadna z nich nie jest w pełni wiarygodna i wymaga dalszej walidacji.

Prognozy Feochromocytoma

Wskaźniki prognostyczne
Czynniki wpływające na rokowanie

Systemy oceny i predykcji potencjału przerzutowego

System PASS (Pheochromocytoma of the Adrenal Gland Scaled Score)
System GAPP (Grading system for Adrenal Pheochromocytoma and Paraganglioma)
Zmodyfikowane systemy oceny
Nomogramy prognostyczne

Znaczenie leczenia chirurgicznego
Monitorowanie i obserwacja
Podsumowanie badań nad prognozą feochromocytoma

Kolejne rozdziały

Prognozy Feochromocytoma

Feochromocytoma (łac. phaeochromocytoma) to rzadki guz neuroendokrynny wywodzący się z rdzenia nadnerczy. Przewidywanie potencjału przerzutowego tego nowotworu stanowi istotne wyzwanie kliniczne, gdyż zgodnie z klasyfikacją WHO z 2017 roku wszystkie feochromocytomy mają potencjał przerzutowy, w przeciwieństwie do tradycyjnego podziału na łagodne i złośliwe guzy w oparciu o obecność przerzutów odległych w momencie diagnozy¹. Choć w diagnozowaniu i przewidywaniu przebiegu choroby wykorzystuje się wiele różnych wskaźników (genetycznych, histopatologicznych, biochemicznych), żaden z nich nie ma 100% skuteczności w przewidywaniu przerzutów²³.

Wskaźniki prognostyczne

W przypadku złośliwego feochromocytoma wskaźniki 5-letniego przeżycia są zróżnicowane w zależności od badania, jednak wskazują na istotne ryzyko śmiertelności. Według niektórych źródeł 5-letnie przeżycie u pacjentów z przerzutowym feochromocytoma wynosi mniej niż 50%⁴, a według innych badań może wynosić zaledwie 11,8%⁵. Z kolei dla pacjentów po radykalnym leczeniu chirurgicznym wskaźniki przeżycia są znacznie lepsze. Badanie populacyjne wykazało, że pacjenci po radykalnym zabiegu chirurgicznym mają 5-letnie i 10-letnie przeżycie po operacji wynoszące odpowiednio 90,8% i 78,7%⁶.

Przeżycie wolne od przerzutów po 5 latach od zabiegu operacyjnego wynosi 87,0%, a po 10 latach – 75,7%⁷. Ogólny wskaźnik 5-letniego przeżycia wolnego od przerzutów w jednym z badań wynosił 84,4%⁸. Te dane podkreślają znaczenie wczesnej diagnozy i radykalnego leczenia chirurgicznego dla pomyślnego rokowania⁹.

Czynniki wpływające na rokowanie

Wyodrębniono szereg czynników, które mogą wpływać na rokowanie u pacjentów z feochromocytoma:

Wielkość guza – guzy o wymiarach powyżej 5,5 cm wiążą się z wyższym prawdopodobieństwem złośliwości¹⁰
Poziom wydalania kwasu wanilinomigdałowego (VMA) – minimalnie podwyższone wydalanie VMA (>2,1 mg/dzień/cm) może wskazywać na wyższe ryzyko złośliwości¹¹
Fenotyp wydzielniczy – wyższe poziomy nor adrenaliny i niższy stosunek adrenaliny do sumy adrenaliny i noradrenaliny są związane z chorobą przerzutową¹²
Wychwyt MIBG – negatywny wychwyt MIBG może być związany z gorszym przeżyciem całkowitym (OS)¹³
Indeks proliferacji Ki67 – wartości Ki67 ≥10% mogą wiązać się z krótszym czasem do progresji choroby¹⁴
Lokalizacja guza – umiejscowienie pod przeponą może być związane z gorszym rokowaniem¹⁵
Funkcjonalność guza – guzy wydzielające katecholaminy mogą mieć gorsze rokowanie¹⁶
Wiek pacjenta – młodszy wiek w momencie diagnozy często wiąże się z bardziej agresywnym przebiegiem choroby, głównie ze względu na korelację z zespołami dziedzicznymi¹⁷
Płeć męska, starszy wiek w momencie diagnozy, podwyższone poziomy dopaminy, synchroniczne przerzuty i nieradykalny zabieg chirurgiczny wiążą się z gorszym rokowaniem¹⁸
Poziom chromograniny A (CgA) – istotnie różni się w łagodnym i przerzutowym feochromocytoma i koreluje z ryzykiem nawrotu¹⁹

Systemy oceny i predykcji potencjału przerzutowego

W celu lepszego przewidywania potencjału przerzutowego feochromocytoma opracowano kilka systemów oceny i klasyfikacji. Żaden z nich nie jest jednak w pełni wiarygodny i wszystkie wymagają dalszej walidacji w badaniach wieloośrodkowych²⁰.

System PASS (Pheochromocytoma of the Adrenal Gland Scaled Score)

PASS jest najwcześniejszym opracowanym systemem oceny, który stanowi podstawę dla późniejszych badań²¹. System ten bazuje na cechach histopatologicznych guza. Wyniki badań wskazują, że wyższe wartości PASS wiążą się z szybszą progresją choroby, a pacjenci z PASS>7 mają istotnie gorsze rokowanie²²²³. Chociaż zdolność systemu PASS do przewidywania przerzutów nie jest zadowalająca, jego wartość w przewidywaniu braku przerzutów nadaje mu dużą wartość w określonych zastosowaniach klinicznych²⁴.

System GAPP (Grading system for Adrenal Pheochromocytoma and Paraganglioma)

System GAPP został opracowany przez Kimurę i współpracowników w 2014 roku jako modyfikacja systemu PASS, w której wykluczono niektóre słabo skorelowane cechy histologiczne²⁵. Wykazano istotną korelację między wynikami GAPP a potencjałem przerzutowym – średnie wyniki GAPP dla grup bez przerzutów i z przerzutami wynosiły odpowiednio 2,08±0,17 i 5,33±0,43²⁶. Stwierdzono również istotną ujemną korelację między wynikiem GAPP a czasem do wystąpienia przerzutów (r=0,438, P<0,01)²⁷. 5-letnie przeżycie pacjentów z niskim, średnim i wysokim wynikiem GAPP wynosiło odpowiednio 100%, 66,8% i 22,4%²⁸.

Zmodyfikowane systemy oceny

W oparciu o system GAPP opracowano zmodyfikowany system oceny dla nadnerczowego feochromocytoma i przyzwojaków (M-GAPP), który łączy utratę barwienia SDHB z istotnymi parametrami systemu GAPP²⁹. Innym systemem jest COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score), który obejmuje trzy cechy kliniczno-histopatologiczne w połączeniu z indeksem proliferacji PS100 i inaktywacją SDHB w celu przewidywania ryzyka przerzutów³⁰.

System ASES wykazuje niską czułość (61%) i specyficzność (80%), z dokładnością przewidywania nieprzerzutowego feochromocytoma na poziomie 97%, ale jedynie 18% w przypadku guzów przerzutowych³¹.

Nomogramy prognostyczne

Opracowano również nomogramy do przewidywania 3- i 5-letniego przeżycia całkowitego (OS) oraz przeżycia specyficznego dla nowotworu (CSS) u pacjentów ze złośliwym feochromocytoma³². Niezależnymi czynnikami prognostycznymi dla OS były: wiek, płeć, typ guza, stadium guza i zabieg chirurgiczny, podczas gdy dla CSS były to: wiek, stadium guza i zabieg chirurgiczny³³. Najistotniejszym wskaźnikiem w obu modelach było stadium guza³⁴. Nomogramy te mogą być wykorzystane jako niezależne narzędzia do oceny rokowania i kierowania spersonalizowanym postępowaniem klinicznym u pacjentów ze złośliwym feochromocytoma³⁵.

Znaczenie leczenia chirurgicznego

Interwencja chirurgiczna ma istotny wpływ na rokowanie pacjentów z feochromocytoma. Badania wykazały, że pacjenci poddani radykalnemu leczeniu chirurgicznemu mają znacznie lepsze rokowanie długoterminowe – około trzech czwartych pacjentów żyje ponad dziesięć lat po operacji³⁶. Natomiast pacjenci, którzy nie przeszli radykalnego zabiegu, stanowią niejednorodną grupę z relatywnie krótką oczekiwaną długością życia³⁷.

Co istotne, nawet w przypadku choroby przerzutowej lub nawrotowej interwencja chirurgiczna skierowana na zmiany przerzutowe znacząco poprawia rokowanie³⁸³⁹. Pacjenci, którzy przeszli operację z powodu przerzutów lub nawrotu choroby, mieli znacznie lepsze wskaźniki przeżycia⁴⁰.

Monitorowanie i obserwacja

Średni czas do wystąpienia przerzutów po początkowej operacji wynosi 5,5±2,6 lat⁴¹, co podkreśla znaczenie długoterminowej obserwacji. Wytyczne Europejskiego Towarzystwa Endokrynologicznego sugerują, że pacjenci z wysokim ryzykiem potencjału przerzutowego powinni być obserwowani przez całe życie, a nie tylko przez 10 lat⁴².

Monitorowanie ciśnienia tętniczego po udanym zabiegu chirurgicznym może dostarczyć wskazówek dotyczących potencjalnego rozwoju późniejszych przerzutów⁴³. Pacjenci z grupy ryzyka powinni przejść bardziej rygorystyczną obserwację z wykorzystaniem technik obrazowania, takich jak pooperacyjna tomografia komputerowa i skanowanie MIBG przez co najmniej 2 lata, oraz badań biochemicznych, takich jak ocena niskiego 24-godzinnego wydalania katecholamin z moczem w ciągu 4 miesięcy po operacji⁴⁴.

Niedawny przegląd systematyczny i metaanaliza oszacowały wskaźnik nawrotów na około 1% rocznie⁴⁵, co potwierdza potrzebę regularnej obserwacji.

Podsumowanie badań nad prognozą feochromocytoma

Ze względu na rzadkość występowania feochromocytoma, dostępne dane dotyczące rokowania są ograniczone i pochodzą głównie z ośrodków referencyjnych, co może prowadzić do potencjalnego błędu selekcji⁴⁶⁴⁷. Ponadto, jakość dostępnych dowodów jest niska ze względu na istotne błędy selekcji i heterogeniczność badań, które często obejmują pacjentów niepoddanych radykalnej terapii, określając jedynie ryzyko choroby przerzutowej⁴⁸.

Mimo że wiele zmiennych zostało powiązanych z rokowaniem feochromocytoma, czy to z genetycznego, histopatologicznego, czy klinicznego punktu widzenia, do tej pory nie istnieją zwalidowane modele wieloczynnikowe ani skale uznane za wiarygodne predyktory potencjału przerzutowego lub ryzyka nawrotu feochromocytoma⁴⁹. Wyniki badań dotyczących potencjalnych czynników prognostycznych powinny być dalej walidowane w niezależnych i większych kohortach⁵⁰.

Podkreśla to potrzebę opracowania prostych i zwalidowanych narzędzi do lepszego określenia agresywności choroby i ustalenia zindywidualizowanego leczenia pacjentów oraz protokołów obserwacji⁵¹. W kontekście nowych odkryć dotyczących potencjału przerzutowego wszystkich feochromocytoma, dokładne przewidywanie tego potencjału nabiera kluczowego znaczenia w praktyce klinicznej⁵².

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Materiały źródłowe

#1 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#2 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#3 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. […] In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patientsâ treatments and follow-ups. […] The clinical signs and symptoms of PPGLs are very variable and non-specific; thus, the consequent delayed or missed diagnosis could be fatal or lead to significant complications and adverse outcomes. PPGLs are also very heterogeneous in the clinical course with a variable prognosis concerning the development of metastases. Despite most of these neoplasms are radically cured by surgery, all PPGLs have potentially metastatic properties, and no reliable clinical, histopathological, or biochemical predictors are established to determine with certainty whether a PPGL could be potentially metastatic. […] Although many studies have examined the potential prognostic role of various clinical, biochemical, genetic, and histopathological features, there is not a single feature that can be used alone to reliably predict tumor recurrence and, therefore, guide clinical practice.
#4 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#5 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#6 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#7 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#8 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#9 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#10 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#11 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#12 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#13 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p = 0.13). […] Our results should be further validated in independent and larger cohorts.
#14 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p = 0.13). […] Our results should be further validated in independent and larger cohorts.
#15 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p = 0.13). […] Our results should be further validated in independent and larger cohorts.
#16 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p = 0.13). […] Our results should be further validated in independent and larger cohorts.
#17 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#18 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#19 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#20 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#21 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#22 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. […] Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. […] A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. […] Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. […] The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. […] The prognosis of metastatic or recurrent PPGL is a major concern for clinicians and patients, as these tumors have a poor prognosis and limited treatment options.
#23 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Our study revealed significantly higher PASS in the rapid progression group. In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our analysis revealed two main findings. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Surgery for recurrent/metastatic disease was associated with better survival rates. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] The prognosis and survival rates for these patients are not well-established.
#24 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#25 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#26 Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma in: Endocrine-Related Cancer Volume 21 Issue 3 (2014)
https://erc.bioscientifica.com/view/journals/erc/21/3/405.xml
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. […] GAPP scores of the non-metastatic and metastatic groups were 2.08Â±0.17 and 5.33Â±0.43 (meanÂ±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5Â±2.6 years. [...] The five-year survival of these groups was 100%, 66.8% and 22.4% respectively. [...] Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.
#27 Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma in: Endocrine-Related Cancer Volume 21 Issue 3 (2014)
https://erc.bioscientifica.com/view/journals/erc/21/3/405.xml
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. […] GAPP scores of the non-metastatic and metastatic groups were 2.08Â±0.17 and 5.33Â±0.43 (meanÂ±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5Â±2.6 years. [...] The five-year survival of these groups was 100%, 66.8% and 22.4% respectively. [...] Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.
#28 Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma in: Endocrine-Related Cancer Volume 21 Issue 3 (2014)
https://erc.bioscientifica.com/view/journals/erc/21/3/405.xml
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. […] GAPP scores of the non-metastatic and metastatic groups were 2.08Â±0.17 and 5.33Â±0.43 (meanÂ±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5Â±2.6 years. [...] The five-year survival of these groups was 100%, 66.8% and 22.4% respectively. [...] Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.
#29 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#30 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#31 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#32 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma […] This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. […] The prediction accuracy of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. […] Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). [...] Based on these factors, we successfully constructed the OS and CSS nomograms. [...] We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL.
#33 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma […] This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. […] The prediction accuracy of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. […] Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). [...] Based on these factors, we successfully constructed the OS and CSS nomograms. [...] We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL.
#34 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
The nomograms could inform personalized clinical management of the patients. […] The most significant indicator on the patientsâ OS and CSS in both models was the tumor stage. […] The OS prediction model comprises of age, gender, tumor type, tumor stage, and surgery, while the CSS prediction model consists of age, tumor stage, and surgery. […] Overall, this study has given insight and laid the foundation for further interrogation of the relationship between demographic features and disease prognosis. […] In conclusion, we have successfully established nomograms for the prediction of 3- and 5-year OS and CSS in patients with PPGL. The nomogram proved to be accurate and reliable in the prediction of the disease outcome. The nomogram can be used as an independent tool to assess the prognosis and guide personalized follow-up for clinical management of malignant PPGL patients.
#35 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
The nomograms could inform personalized clinical management of the patients. […] The most significant indicator on the patientsâ OS and CSS in both models was the tumor stage. […] The OS prediction model comprises of age, gender, tumor type, tumor stage, and surgery, while the CSS prediction model consists of age, tumor stage, and surgery. […] Overall, this study has given insight and laid the foundation for further interrogation of the relationship between demographic features and disease prognosis. […] In conclusion, we have successfully established nomograms for the prediction of 3- and 5-year OS and CSS in patients with PPGL. The nomogram proved to be accurate and reliable in the prediction of the disease outcome. The nomogram can be used as an independent tool to assess the prognosis and guide personalized follow-up for clinical management of malignant PPGL patients.
#36 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#37 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#38 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. […] Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. […] A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. […] Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. […] The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. […] The prognosis of metastatic or recurrent PPGL is a major concern for clinicians and patients, as these tumors have a poor prognosis and limited treatment options.
#39 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Our study revealed significantly higher PASS in the rapid progression group. In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our analysis revealed two main findings. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Surgery for recurrent/metastatic disease was associated with better survival rates. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] The prognosis and survival rates for these patients are not well-established.
#40 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Our study revealed significantly higher PASS in the rapid progression group. In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our analysis revealed two main findings. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Surgery for recurrent/metastatic disease was associated with better survival rates. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] The prognosis and survival rates for these patients are not well-established.
#41 Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma in: Endocrine-Related Cancer Volume 21 Issue 3 (2014)
https://erc.bioscientifica.com/view/journals/erc/21/3/405.xml
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. […] GAPP scores of the non-metastatic and metastatic groups were 2.08Â±0.17 and 5.33Â±0.43 (meanÂ±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5Â±2.6 years. [...] The five-year survival of these groups was 100%, 66.8% and 22.4% respectively. [...] Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.
#42 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#43 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#44 :: ICU :: Investigative and Clinical Urology
https://icurology.org/DOIx.php?id=10.4111/kju.2011.52.4.241
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. […] Large tumor size (5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery. […] The overall 5-year metastasis-free survival rate was 84.4%. […] The 5-year survival rate of patients with malignant pheochromocytoma was 11.8%. […] Monitoring arterial blood pressure after successful surgery may provide a clue for potential development of subsequent metastasis. […] These findings suggest that patients at risk should undergo more rigorous follow-up with the use of imaging modalities such as postoperative CT and MIBG scanning for at least 2 years and with the use of biochemical modalities such as low 24-hour urinary catecholamine excretion within 4 months after surgery.
#45 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#46 Mortality in patients with Pheochromocytoma: a population-based study 1977–2016 | ECE2018 | 20th European Congress of Endocrinology | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0056/ea0056gp44
Mortality in patients with Pheochromocytoma: a population-based study 1977-2016 […] Due to the rarity, limited data on prognosis exists and data are mainly from tertiary centers with potential referral bias. […] Radically operated (n=162, 81.8%) patients (median age 52.0 years (Q1Q3: 39.363.0)) had an overall 5- and 10-year survival after surgery of 90.8% (CI95%: 84.594.6) and 78.7% (CI95%: 69.885.2) and a recurrence-free 5- and 10-year survival of 87.0% (CI95%: 80.191.7) and 75.7% (CI95%: 66.782.7), respectively. […] PPGL patients who undergo radical surgery have a good long-term prognosis with three-fourths of patients living more than ten years after surgery. […] Those who are not radically operated are a heterogeneous patient group with a relatively short life expectancy. […] This, combined with the fact that PPGL was considered a direct or contributing cause of death in many patients diagnosed at autopsy, underlines the importance of early diagnosis and treatment of PPGL.
#47 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
The first scoring system proposed is the pheochromocytoma of the adrenal gland scaled score (PASS), elaborated through a retrospective study conducted on a cohort of 100 PCC cases. […] The authors found a positive correlation between GAPP score and metastatic potential and a negative correlation with metastasis-free interval. […] The authors showed that this score is able to correlate with progression-free survival (PFS) and metastatic behavior. […] Clinical experience on this topic is difficult to achieve due to the low prevalence of PPGLs. […] Although several variables have been found to be associated with PPGLs prognosis, either from a genetic, histopathological, or clinical point of view, to date there are still no validated multivariable models or scores recognized as reliable predictors of PPGL metastatic potential or recurrence risk.
#48 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
A recent systematic review and meta-analysis estimated a recurrence rate of around 1% every year. […] The authors also showed that poorer prognosis was related to male gender, larger primary tumor size, older age at diagnosis, elevated dopamine levels, synchronous metastases, and non-radical surgery. […] However, the authors highlighted scarce quality of the available evidence due to important referral bias and heterogeneity of the studies that often include patients not radically cured, defining only the risk of metastatic disease. Therefore, they concluded that further research is needed to obtain prognostic information in this field. […] Younger age at diagnosis is typically associated with more aggressive disease, mainly due to the correlation with hereditary syndromes. […] The literature data showed that the recurrence risk of PPGLs is associated with the secretory phenotype, reflected by higher norepinephrine levels and lower epinephrine/epinephrine + norepinephrine ratio in metastatic disease. […] The prognostic value of chromogranin A (CgA) was also explored in the literature. Rao et al. observed that CgA was significantly different in benign versus metastatic PCCs, and they also found a correlation between CaA levels and recurrence risk.
#49 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
The first scoring system proposed is the pheochromocytoma of the adrenal gland scaled score (PASS), elaborated through a retrospective study conducted on a cohort of 100 PCC cases. […] The authors found a positive correlation between GAPP score and metastatic potential and a negative correlation with metastasis-free interval. […] The authors showed that this score is able to correlate with progression-free survival (PFS) and metastatic behavior. […] Clinical experience on this topic is difficult to achieve due to the low prevalence of PPGLs. […] Although several variables have been found to be associated with PPGLs prognosis, either from a genetic, histopathological, or clinical point of view, to date there are still no validated multivariable models or scores recognized as reliable predictors of PPGL metastatic potential or recurrence risk.
#50 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p = 0.13). […] Our results should be further validated in independent and larger cohorts.
#51 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. […] In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patientsâ treatments and follow-ups. […] The clinical signs and symptoms of PPGLs are very variable and non-specific; thus, the consequent delayed or missed diagnosis could be fatal or lead to significant complications and adverse outcomes. PPGLs are also very heterogeneous in the clinical course with a variable prognosis concerning the development of metastases. Despite most of these neoplasms are radically cured by surgery, all PPGLs have potentially metastatic properties, and no reliable clinical, histopathological, or biochemical predictors are established to determine with certainty whether a PPGL could be potentially metastatic. […] Although many studies have examined the potential prognostic role of various clinical, biochemical, genetic, and histopathological features, there is not a single feature that can be used alone to reliably predict tumor recurrence and, therefore, guide clinical practice.
#52 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. European Society of Endocrinology Clinical Practice Guideline suggested that patients with high risk of metastatic potential should be followed-up for lifetime instead of 10 years. A precise prediction of metastatic potential would be important. Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies. The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) was designed by Kimura et al both for pheochromocytoma and paraganglioma in 2014, which was based on the PASS grading system by excluding some poorly concordant histological features and aimed to predict the metastatic potential and the prognosis of patients. The modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP) was proposed by Koh et al in 2017, which is a combination of the loss of SDHB staining and some significant parameters in the GAPP grading system. The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival. Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.