Doubling Time of Residual Tumor Volume for Metastatic Neuroendocrine Tumors Determines Survival Outcomes after Hepatic Resection

Abstract

Introduction: Estimates of the percentage of resectable tumor to guide debulking surgery for metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) does not account for tumor biology and absolute hepatic tumor burden. Thus, we studied the growth kinetics of residual metastatic disease after debulking surgery for GEP-NET to determine whether these tumor-specific factors correlated with survival. Methods: Patients with measurable residual metastatic disease by imaging after debulking surgery for GEP-NET with or without resection of primary tumors between 2000-2017 were studied. Residual tumor volumes were measured over time to determine tumor growth kinetics. The primary outcome of interest was time from debulking surgery to adjuvant therapy or death. Results: Twenty-eight patients had residual metastatic GEP-NET and half had an estimated ≥90% debulking resection. Median residual tumor volume (Y0) after debulking surgery was 3.0 (IQR 0.45-20.8) ml. Median tumor volume doubling time was 53.9 (IQR 29-159.2) weeks. Grade of tumor differentiation, Ki-67 index, and estimated percentage of debulking were not associated with outcomes. Multi-variate analysis showed that, after adjusting for Y0 and the use of somatostatin-analogues post-operatively, only tumor volume doubling time ≥52 weeks was associated with the time to adjuvant therapy or death (HR 0.17 95%CI 0.04-0.82). Patients with a tumor doubling time ≥52 weeks had improved overall survival at 1, 3, and 5 years when compared to a doubling time < 52 weeks (100.0%, 90.9%, 90.9% vs 92.3%, 68.4%, 68.4%; p=0.034). Conclusions: Tumor volume doubling time, not the proportion of debulking performed, determines outcomes after debulking surgery for residual metastatic GEP-NET.