Incidental Gallbladder Cancer: Residual Cancer Discovered at Oncologic Extended Resection Determines Outcome: A Report from High- and Low-Incidence Countries

Background: Gallbladder cancer detected incidentally after cholecystectomy (IGBC) currently is the most common diagnosis of gallbladder cancer, and oncologic extended resection (OER) is recommended for tumors classified higher than T1b. However, the precise prognostic significance of residual cancer (RC) found at the time of OER has not been well established. This analysis aimed to determine the prognostic impact of RC found in patients with IGBC undergoing OER. Methods: Outcomes for IGBC at a center for a low-incidence country (USA) and a high-incidence country (Chile) between January 1999 and June 2015 were analyzed. Residual cancer was defined as histologically proven cancer at OER. Predictors of disease-specific survival (DSS) were analyzed. Results: Of 187 patients, 171 (91.4%) achieved complete resection (R0) at OER. The rates of surgical mortality and severe morbidity were respectively 1.1 and 9.6%. Of the 187 patients, 73 (39%) had RC. Perineural invasion and/or lymphovascular invasion and T3 stage were associated with the presence of RC. In both countries, RC was associated with a significantly shorter median survival (23% vs not reached; p < 0.001) and lower 5-year DSS rate (19% vs. 74%; p < 0.001) despite R0 resection. In the multivariable analysis, RC was an independent poor predictor of DSS (hazard ratio [HR], 4.00; 95% confidence interval [CI], 2.13–7.47; p < 0.001), as were lymphovascular and/or perineural invasion (HR, 1.95; 95% CI, 1.19–3.21; p = 0.008). Conclusions: The presence of RC in patients undergoing OER for IGBC is associated with poor DSS in both high- and low-incidence countries, even when R0 resection is achieved. Residual cancer defines a high-risk cohort for whom adjuvant therapy may be beneficial.