Perioperative chemotherapy for clinical stage IIIB gallbladder cancer: a review of the National Cancer Database

Abstract Background Gallbladder cancer is rare with high mortality and limited treatments. Patients with IIIB disease (T1-3, N1, M0) are typically not offered resection and may receive palliative chemotherapy. This study evaluates survival of IIIB patients undergoing surgery with or without systemic therapy. Methods Patients with stage IIIB gallbladder cancer who underwent curative-intent surgery were identified from the National Cancer Database (2004–2020). Outcomes were analyzed by chemotherapy sequence using Kaplan-Meier curves and Cox proportional hazards models. Lymphadenectomy type and margin status were also compared. Results 409 patients were included. Mean age was 60 in neoadjuvant, 65 in adjuvant and 72 in no chemotherapy classes ( p < 0.01). The median overall survival (OS) in months was 33.8 (95% CI 23.8 - NA) in neoadjuvant, 22.6 (95% CI 19.8–27.2) in adjuvant and 9.4 (95% CI 7.3–14.3) in no chemotherapy groups ( p < 0.01). Compared to adjuvant therapy, hazard ratios (HR) for OS were 0.76 (95% CI 0.46–1.26, p = 0.29) for neoadjuvant and 1.87 (95% CI 1.45–2.42, p < 0.01) for no chemotherapy. Age, tumor size, number of positive regional nodes, and positive margins (R1) were significant covariables. Regional lymphadenectomies were performed in 79%, 87%, and 84% for neoadjuvant, adjuvant, and no chemotherapy classes. R0 margins were obtained in 86%, 76%, and 81%, respectively. Conclusion Surgery with systemic therapy should be considered in stage IIIB gallbladder cancer. Perioperative chemotherapy was associated with longer survival but occurred more in younger patients. Perioperative chemotherapy, particularly neoadjuvant, may benefit appropriately selected patients.