A Nationwide Analysis of Adjuvant Therapy Use after Inadequate Operation for Early-Stage Gallbladder Cancer

INTRODUCTION: Most patients with T1b-T3 gallbladder cancer do not undergo adequate oncologic resection. Adjuvant therapy is guideline indicated after oncologic resection of T1b-T3 gallbladder cancer; however, the role of adjuvant therapy after inadequate operation, cholecystectomy alone, is undefined. We describe adjuvant therapy use after inadequate operation for T1b-T3 gallbladder cancer. METHODS: Using the National Cancer Database, we identified patients who underwent operation for T1b-T3 gallbladder cancer between 2004 and 2016. Those who underwent cholecystectomy alone were analyzed by adjuvant treatment: none, chemotherapy, or chemoradiotherapy. Survival by treatment strategy was described using Kaplan-Meier and Cox proportional hazard models. RESULTS: Of 3,076 patients who underwent operation for T1b-T3 gallbladder cancer, 2,060 (67%) underwent cholecystectomy alone. Among these, most were older than 65 years (66%), female (72%), non-Hispanic White (64%), and had a Charlson Comorbidity Index of 0 (69%). After cholecystectomy alone, 62% received no adjuvant therapy, 23% received chemotherapy, and 15% received chemoradiotherapy. For patients with T1b/T2 tumors (n = 1,211) and T3 tumors (n = 875), adjuvant chemoradiotherapy improved survival over adjuvant chemotherapy. Adjusting for patient characteristics, there was a statistically significant decreased hazard of death with adjuvant chemoradiotherapy relative to adjuvant chemotherapy or inadequate operation alone (p < 0.05). Chemoradiotherapy was associated with improved overall survival relative to chemotherapy for all T stages with positive nodes or margins (p ≤ 0.05). CONCLUSION: Most patients do not receive adjuvant therapy after inadequate operation for T1b-T3 gallbladder cancer. Adjuvant chemoradiotherapy was significantly associated with improved survival after cholecystectomy alone for T1b-T3 gallbladder cancer and should be considered for these surgically undertreated patients.