Integrating Tumour Biology into Surgical Decision-Making for Metastatic Colorectal Cancer: A Real-World Cohort Analysis Adapted for Clinical Colorectal Cancer

Background: Metastatic colorectal cancer (mCRC) is biologically heterogeneous, resulting in variable outcomes despite similar disease burden and treatment. Although metastasectomy offers the only potentially curative option for selected patients, surgical selection remains largely anatomy based. Whether biological factors continue to influence outcomes after resection remains unclear. Methods: We retrospectively analysed 290 consecutive patients with stage IV colorectal adenocarcinoma treated at a Brazilian tertiary oncology centre (2003–2019). Tumour sidedness, RAS mutational status, and metastasectomy were evaluated for overall survival (OS) using Kaplan–Meier analysis and multivariable Cox regression in the overall cohort and the metastasectomy subgroup. Results: Median OS was 40.2 months. Patients undergoing metastasectomy had significantly longer survival than those managed non-operatively (median 116.0 vs. 30.1 months; 5-year OS 63% vs. 14%; p < 0.001). The following variables remained independently associated with improved survival: metastasectomy (HR 4.58, 95% CI 2.82–7.44; p < 0.001), RAS status (wild type vs. mutated: HR 2.77, 95% CI 1.65–4.64; p < 0.001), age (>70 ys vs. ≤ 70 HR 0.58, 95% CI 0.37–0.92; p = 0.021) and metastatic presentation (synchronous vs. metachronous: HR 0.61 95% CI 0.39–0.95; p = 0.028). RAS status remained associated with survival in patients undergoing metastasectomy (HR 3.75, 95% CI 1.46–9.60; p = 0.006). Conclusions: Tumour biology remains a dominant determinant of survival in mCRC even after metastasectomy. These data challenge purely anatomy-based surgical paradigms and support integrating molecular and clinicopathological risk into post-resection management and treatment planning.