Assessing prognosis of neuroendocrine neoplasms: Results of a collaborative multinational effort including over 10.000 european patients-The ENETS registry
Abstract
Background: Global European high quality epidemiologic data on Neuroendocrine Neoplasms (NEN) are lacking. There is limited knowledge on the contribution of prognostic factors on patient (pt) management.
Methods: The multinational ENETS registry (www.enets.org/the_registry.html) was launched in 2015. To date, data from 7 countries (Belgium, Czech republic, Germany, Greece, Poland, Spain, Switzerland) were analyzed, including age, gender, primary site, functional syndrome, WHO grade, stage according to TNM/ENETS, treatment modalities and overall survival (OS).
Results: High quality data from 10.102 pts are presented. Median age at diagnosis is 59 y (10-102y), female represent 48%.
Pancreas (2722 pts, 26%) and small intestine (2132 pts, 21%) NEN are the most frequent primaries. Functional syndrome is present in 26.9% of pts, 80% being carcinoid syndrome.
Stage at diagnosis (n = 6297 pts) is IV in 46%, III in 16%, II in 11% and I in 27%. WHO grading (n = 7400) is G1 in 48%, G2 in 36% and G3 in 16%.
Among metastatic pts (46% of total), liver is the most frequent site (77%), followed by lymph nodes (44%), bone, lung and peritoneum (10-15%). Surgery was performed in 71%, somatostatin analogues were given to 1/3 of pts, chemotherapy to 20%, molecular targeted therapies to 8% and PRRT to 9%.
Median OS of all pts is 178 months. Five-year and 10-year OS are 74.5% and 60.9% respectively.
OS is influenced by grade (G1: 279 months, G2: 167m, G3: 18m) and stage (I: Not reached, II: 225m, III: 160m, IV: 75m). Multivariable analyses show that grade and stage are independent predictors of OS: grade 2 vs grade 1 (HR 1.49, p < 0.001), grade 3 vs grade 1 (HR 7.56, p < 0.001), stage 3 vs stage 1 (1.59, p = 0.001) and stage 4 vs stage 1 (HR 3.99, p < 0.001).
Conclusions: This analysis represents the largest multinational dataset of NEN patients to date, and highlights the crucial role of WHO grading (Ki67) for predicting patients' prognosis. In addition, it provides valuable information on patients' demographics, tumor characteristics and applied therapies.