Real-World Survival Outcomes Following Metastasectomy in RAS Wild-Type mCRC: Insights from a Multicentre National Cohort Study

Abstract

Background: Metastasectomy is a cornerstone of multimodal management in metastatic colorectal cancer (mCRC), yet contemporary real-world data focusing specifically on RAS wild-type (RAS-WT) disease remain limited. We aimed to evaluate survival outcomes and prognostic factors associated with metastasectomy in patients with RAS-WT mCRC using a large national multicentre registry. Methods: This retrospective cohort study utilized data from the ONKO-KOLON T & uuml;rkiye registry. A total of 1079 patients with pathologically confirmed KRAS/NRAS wild-type mCRC were identified and categorized according to receipt of metastasectomy. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with log-rank tests across multiple clinically relevant time origins, including metastatic diagnosis, initial colorectal cancer diagnosis, and time of metastasectomy. Prognostic factors within the metastasectomy cohort were assessed using univariate Cox proportional hazards models. Serum CEA and CA19-9 were analyzed after log10 transformation. Results: Among 1079 patients, 185 (17.1%) underwent metastasectomy. Patients receiving metastasectomy demonstrated significantly longer OS compared with those managed non-surgically when survival was calculated from the time of metastatic diagnosis (hazard ratio [HR] for death 0.36, 95% CI 0.27-0.47; p < 0.001), as well as improved PFS (HR for progression or death 0.39, 95% CI 0.30-0.52; p < 0.001). The survival advantage remained consistent when OS was measured from the time of initial colorectal cancer diagnosis (HR 0.37, 95% CI 0.25-0.50; p < 0.001). Median OS following metastasectomy was 43 months (95% CI 31.4-45.6). In univariate analyses within the metastasectomy cohort, higher baseline CA19-9 levels were significantly associated with inferior OS when analyzed both as a continuous variable (per log10 increase; HR 1.81, 95% CI 1.20-2.75; p = 0.005) and as a categorical variable (above vs. below threshold; HR 0.37, 95% CI 0.16-0.86; p = 0.021). Other clinicopathologic factors, including age, CEA, tumor sidedness, grade, MSI status, and metastatic burden, were not significantly associated with survival. Conclusions: In this large, real-world national cohort of RAS-WT mCRC, metastasectomy was strongly associated with prolonged survival across multiple clinically relevant time frames. Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC.