Comprehensive Complication Index Predicts Cancer-specific Survival After Resection of Colorectal Metastases Independent of RAS Mutational Status

Objective: To investigate prognostic impact of postoperative complications for colorectal liver metastases (CLM) in the era of RAS mutation analysis. Background: Postoperative complications have been associated with cancer-specific outcomes in multiple malignancies. Methods: We identified 575 patients with known RAS mutation status who underwent hepatic resection for CLM during 2008 to 2014. Postoperative complications were scored with the comprehensive complication index (CCI), and the neutrophil-to-lymphocyte ratio (NLR) was used as an indicator of systemic inflammation before and after surgery. Survival after resection of CLM was stratified by CCI (high, ≥26.2; low, <26.2). Results: Eighty-eight patients had high and 487 low CCI. Recurrence-free survival (RFS) and cancer-specific survival (CSS) after hepatic resection were worse in patients with high CCI than in patients with low CCI (RFS at 3 yrs 26% vs. 41%, P = 0.003; CSS at 5 yrs 46% vs. 64%, P = 0.003). High CCI (odds ratio 3.99, P <0.001) was associated with high NLR (>5) 3 months after hepatic resection. Five factors were associated with worse CSS: high CCI [hazard ratio (HR) 1.61, P = 0.022], primary positive node (HR 1.70, P = 0.003), multiple CLM (HR 1.72, P = 0.001), CLM ≥3 cm (HR 1.73, P <0.001), and mutant RAS (HR 2.04, P <0.001). Receiver operating characteristic and area under receiver operating characteristic curves revealed CCI to be a more sensitive, specific, and accurate predictor of RFS and CSS than NLR. Conclusions: High CCI is a potent predictor of worse RFS and CSS after resection of CLM. The ramifications of postsurgical complications extend beyond direct influence on patient outcomes to impact cancer-related survival.