Interplay of Tumor Morphology and Biology with Postoperative Complications: Prognostic Implications After Resection of Colorectal Liver Metastasis

Abstract Objective We sought to evaluate the differential prognostic impact of postoperative complications on recurrence-free survival (RFS) and overall survival (OS) relative to clinicopathologic and clinical biologic indicators associated with colorectal liver metastases (CRLM). Methods Patients who underwent curative-intent resection for CRLM between 2000 and 2023 were identified from an international, multi-institutional database. The Genetic And Morphological Evaluation (GAME) score was utilized to risk stratify patients based on KRAS status, carcinoembryonic antigen levels, primary tumor lymph node metastasis, tumor burden score, and extrahepatic disease. The comprehensive complication index (CCI) was used to categorize postoperative complications. Results Among 887 patients included in the analytic cohort, the overall incidence of postoperative morbidity was 22. 3% (n = 197), with 18. 8% (n = 167) of patients having a high CCI (≥ 26. 2). Overall, on multivariable Cox regression analysis, high CCI was independently associated with worse RFS (hazard ration HR 1. 45 95% confidence interval CI 1. 18 – 1. 78; p = 0. 001) but not with OS (HR 1. 14 95% CI 0. 98 – 1. 27; p = 0. 075). Among patients with a low GAME score, high CCI was associated with both worse RFS (HR 2. 17 95% CI 1. 55 – 3. 03; p = 0. 001) and worse OS (HR1. 78 95% CI 1. 22 – 2. 58; p = 0. 001). In contrast, among patients with medium- and high-risk GAME scores, high CCI was associated with neither RFS (HR 0. 97 95% CI 0. 70 – 1. 34; p = 0. 540) nor OS (HR 0. 99 95% CI 0. 67 – 1. 46; p = 0. 290). Conclusion Postoperative complications had a variable prognostic impact on patients undergoing resection for CRLM depending on the severity of the complication and the overall biologic risk of the underlying disease. Patients with more favorable underlying tumor biology were more likely to have adverse oncologic long-term outcomes after experiencing severe postoperative complications.