Peptide Receptor Radionuclide Therapy Improves Survival in Patients Who Progress After Resection of Gastroenteropancreatic Neuroendocrine Tumors

Abstract

Background: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). We investigated a 2-decade experience with PRRT to determine whether PRRT confers a survival advantage to patients who progress after surgery versus other therapies. Methods: We identified patients from our clinic who had resection/cytoreduction of GEP-NETs, then disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan–Meier method assessed progression-free survival (PFS) and overall survival (OS), calculated from progression after surgery (no-PRRT group) or the start of PRRT. Cox regression with time-dependent covariates controlled for immortal time bias and other confounders. Results: Overall, 237 patients progressed after surgery; 95 received PRRT and 142 did not. No differences existed in sex, T or N stage, tumor grade/differentiation, primary site, or time to progression; 94% of PRRT patients had metastases at diagnosis versus 77% in the no-PRRT group. Median PFS was longer in the PRRT group versus the no-PRRT group (32.4 vs. 11.0 months, p < 0.001), as was median OS (49.8 vs. 38.4 months; p = 0.009). In subgroup analysis, the PRRT group had improved PFS in small bowel NETs and pancreatic NETs. Time-dependent covariate analysis revealed a lower risk of death associated with PRRT (hazard ratio 0.61, p = 0.028) after adjusting for sex, age, M stage, tumor grade, and primary site. Conclusion: Surgical resection and cytoreduction is an effective treatment for patients with GEP-NETs, but most patients with metastatic disease develop recurrent disease. Surgery followed by PRRT after progression conferred superior PFS and OS over no PRRT/other therapies, and is an effective strategy for managing patients with GEP-NETs.