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

Background Tumor biomarkers (TBMs) reflect disease burden and correlate with survival for small bowel neuroendocrine tumors (SBNETs). This study sought to determine the performance of chromogranin A (CgA), pancreastatin (PST), neurokinin A (NKA), and serotonin (5HT) during follow-up assessment of resected SBNETs. Methods An institutional database identified patients undergoing surgery for SBNETs. Tumor biomarker levels were assessed as categorical (normal vs elevated) and continuous variables for association with progression-free survival (PFS) and overall survival (OS) via the Kaplan-Meier method with Cox multivariable models adjusted for confounders. Sensitivity, specificity, and predictive values of TBM levels in identifying imaging-confirmed progression were calculated. Results 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, 49.6 months). 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). Conclusion 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 PST should replace CgA for SBNET surveillance.

Automated summary

This study found that elevated levels of CgA, PST, and NKA during follow-up after surgery for SBNETs were associated with lower progression-free survival and overall survival, with PST demonstrating better discrimination of outcomes. Using PST most accurately detected disease progression during the follow-up period.