Improving survival prognostication of gastroenteropancreatic neuroendocrine neoplasms: Revised staging criteria.
Current staging criteria for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), while useful, have limitations. In this study, we used a population-based registry to evaluate the prognostic utility of the current staging systems and assess whether evidence-based modifications can improve survival predictions.



We identified patients with confirmed GEP-NENs from the Surveillance, Epidemiology and End Results registry. We assigned tumour-node-metastasis status according to American Joint Committee on Cancer and European Neuroendocrine Tumor Society criteria. We derived a revised staging classification using Kaplan-Meier methods and Cox regression to assess disease-specific survival and compared the accuracy of potential models based on the Akaike Information Criterion (AIC) and Harrell's C-index. The revised classification was validated in an independent set.



We identified 10,268 patients with GEP-NENs. We found that multiple stages, as determined by current criteria, misclassified patients' prognosis. In particular, stage IIIB (T1-4N1) had overlapping survival with stage IIIA (T4N0). A revised system which reclassifies N1 disease into different stages based on T status (T1-2N1, T3N1 and T4N1) had an improved AIC (difference = 38) and C-index (0.86) compared to current staging. These revisions improved predictions in patients with both low and high-grade tumours from all primary sites. Results also were confirmed across all primary sites in the validation set.



Current staging guidelines misclassify the prognosis of N1 patients. Our results suggest that a revised system could lead to better prognostication for GEP-NEN patients. Further validation followed by implementation of these revisions may improve treatment selection and design of clinical trials.
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA.
Jacob A
JA
Martin
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA.
Richard R P
RR
Warner
Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA.
Juan P
JP
Wisnivesky
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA. Electronic address: michelle.kim@mountsinai.org.
Michelle Kang
MK
Kim
D000328:Adult; D000368:Aged; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000145:classification / Q000401:mortality / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D018426:SEER Program; D015996:Survival Rate
Carcinoid; Gastroenteropancreatic neuroendocrine tumours; Neuroendocrine tumour; Prognosis; Staging; Survival analysis