Survival outcomes associated with treatment modalities in stage 4 gallbladder neuroendocrine tumors: A nationwide analysis.

Abstract

e16295 Background: Gallbladder neuroendocrine tumors (GNETs) are rare, heterogeneous, and aggressive tumors of the gallbladder. GNETs usually present in the elderly ( > 60 years) and there are no clear clinical guidelines to treat stage 4 GNETs due to rarity. We evaluated therapeutic options for stage 4 GNETs. Methods: We included stage 4 GNETs diagnosed between 2004-2020 in the National Cancer Database. Treatment was stratified into combination therapy (Comb) - surgery (Sx) and chemotherapy (CT), Sx alone and CT alone. Survival outcomes were expressed as Kaplan-Meier curves and Cox proportional hazard model adjusting for age, Charlson-Deyo score (CDS) and sociodemographic variables like sex, race, ethnicity, insurance status, and facility location. We expressed survival outcomes as median overall survival (mOS, 95% CI) and time-dependent survival as hazard ratio (HR, 95% CI). Results: Of 242 patients with stage 4 GNETs, the median age was 64 years (range 29-90+ years), 62.4% were female, 66.9% had CDS of 0, 22.4% had CDS of 1, 10.8% had CDS ≥2, 98.7% had poorly differentiated tumor (grade 3 or 4), 70.3% were White, 85.9% were non-Hispanic, median size of the primary tumor was 10.7 cm (range 0.8-14.1 cm) and 47.8% were treated at academic or research program. 46 (19.0%) patients received Comb, 171 (70.7%) received CT and 25 (10.3%) patients received Sx alone. The mOS was 11.5 months (9.3-18.4), 9.4 months (7.9-11.2), 4.2 months (2.3-6.3) for Comb, CT and Sx, respectively (P < 0.001). Pairwise log-rank revealed no significant differences between Comb and CT groups (P = 0.07). In univariate Cox analysis, CDS ≥2 showed HR of 1.6 (1.0-2.4; p = 0.04), Sx showed HR of 1.7 (1.1-2.7; P = 0.02), and Medicare had HR of 1.35 (1.02-1.78; p = 0.037). However, on multivariate analysis, uninsured patients (HR = 5.16; 95% CI 1.50-17.7; P = 0.009) and those receiving Sx alone (HR = 2.09; 95% CI 1.27-3.46; P = 0.004) had unfavorable outcomes. Conclusions: The combination of primary site surgery with CT improves survival in stage 4 GNETs as compared to resection alone. However, there is no significant difference in survival in combination therapy and CT. We emphasize the need for robust prospective studies comparing the efficacy of chemotherapy, neoadjuvant and adjuvant chemotherapy for stage 4 GNETs.[Table: see text]