Survival benefit of adjuvant chemotherapy for perihilar cholangiocarcinoma: Impact of log odds of metastatic lymph node count

Objective: We hypothesized that log odds of metastatic lymph nodes may be an indicator of cancer burden in perihilar cholangiocarcinoma and be used to identify patients who would benefit most from adjuvant chemotherapy. We sought to investigate the interplay between log odds of metastatic lymph nodes and survival benefit of adjuvant chemotherapy in patients with perihilar cholangiocarcinoma. Methods: Data on patients undergoing curative-intent resection with lymph node dissection for perihilar cholangiocarcinoma were obtained from an international multi-institutional database. Overall survival was examined using multivariable Cox proportional hazards models, including an interaction term between log odds of metastatic lymph nodes and receipt of adjuvant chemotherapy. Results: Among 388 patients, the median log odds of metastatic lymph nodes was -1.7 (interquartile range: -2.7, -1.1). On multivariable Cox regression, preoperative carbohydrate antigen 19-9 (hazard ratio 1.00, 95% confidence interval 1.00-1.00, P = .035) and undifferentiated tumors (hazard ratio 1.43, 95% confidence interval 1.05-1.95, P = .023) were independent predictors of overall survival. Notably, there was an interaction between log odds of metastatic lymph nodes and adjuvant chemotherapy (hazard ratio 0.79, 95% confidence interval 0.64-0.99, P = .039). In restricted cubic spline analysis, patients with log odds of metastatic lymph nodes ≥ -2.0 were more likely to benefit from adjuvant chemotherapy, whereas patients with log odds of metastatic lymph nodes < -2.0 demonstrated no survival advantage. Among 228 patients with log odds of metastatic lymph nodes ≥ -2.0, adjuvant chemotherapy was associated with improved overall survival (31.3 months vs 20.1 months, P = .030), whereas there was no survival benefit in 160 patients with log odds of metastatic lymph nodes < -2.0 (69.2 months vs 51.0 months, P = .560). Conclusion: Log odds of metastatic lymph nodes is a predictor of survival benefit from adjuvant chemotherapy in perihilar cholangiocarcinoma. Patients with log odds of metastatic lymph nodes ≥ -2.0 derived survival benefits from adjuvant chemotherapy, whereas patients with log odds of metastatic lymph nodes < -2.0 did not, highlighting the utility of log odds of metastatic lymph nodes to guide adjuvant treatment.