A single institution's 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram

Abstract

Objective: To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature.

Background: The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease.

Methods: Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration.

Results: Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74.

Conclusions: Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

FIGURE 1

A, Kaplan-Meier Survival Curves for 2010 AJCC Staging System. B, Kaplan-Meier Curve for 2006 ENETS Staging System. C, Kaplan-Meier Curve for WHO Ki-67 Grading System.

FIGURE 2

Nomogram for predicted survival of those with nonsyndromic, nonfunctional PanNETs based on our proposed model (grade, age, and sex). ^*Sum together ‘Points’ from Ki-67, age at surgery (≤ 63, > 63) and sex collected from the first line and then find the corresponding result on the ’Total Points’ line. From the Total Points’ line, find the corresponding 5-year overall survival and median survival time. For example, a female patient (’Points’ = 0) who is 75-years old at surgery (’Points’ = 18) and has a PanNET surgical specimen with a Ki-67 index of 3% (’Points’ = 50) has a ’Total Points’ of 68 which corresponds to a 5-year overall survival of approximately 76% with a median overall survival time of 9 years.