It Is Time to Rethink Biomarkers for Surveillance of Small Bowel Neuroendocrine Tumors.

Abstract

Tumor biomarkers(TBMs)reflect disease burden andcorrelate withsurvival for small bowel neuroendocrine tumors (SBNETs).This study sought to determine the performance ofchromogranin A (CgA),pancreastatin(PST), neurokinin A (NKA), and serotonin (5HT) duringfollow-up assessmentof resected SBNETs. An institutional database identified patients undergoing surgery for SBNETs. Tumor biomarker levels were assessed as categorical (normal vs elevated) and continuous variables for association withprogression-free survival (PFS) and overall survival (OS)viathe Kaplan-Meier method withCoxmultivariable models adjusted for confounders. Sensitivity, specificity, and predictive values ofTBMlevels in identifying imaging-confirmed progression werecalculated. In 218 patients (44% female, 92% node + , 73% metastatic, 97% G1 or G2), higher levels of CgA, PST, NKA, and 5HT correlated with higher-grade and metastatic disease at presentation (p < 0.05). Elevated pre- and postoperative CgA, PST, and NKA correlated with lower PFS and OS (p < 0.05; median follow-up period, 49.6months). Normal CgA, PST, and NKA were present in respectively 20.3%, 16.9%, and 72.6% of the patients with progression, whereas elevated levels were present in respectively 69.5%, 24.8%, and 1.3% of the patients without progression. Using TBMs to determine progression showed superiority of PST (78.9% accuracy) over CgA (63.3% accuracy) or CgA and PST together (60.3% accuracy). Although specific for progression, NKA was rarely elevated, limiting its usefulness. Pre- and postoperative PST and CgA correlated with disease burden and survival, with PST providing better discrimination of outcomes. During the follow-up period, use of PST most accurately detected progression. These results suggest that PSTshouldreplaceCgAforSBNET surveillance.