Prognostic Significance of Skin Toxicity in Patients with Ras Wild-Type Metastatic Colorectal Cancer Treated with...

Background and Aim: Anti-epidermal growth factor receptor (EGFR) therapy is commonly associated with skin toxicity, which may reflect treatment response. This study evaluated the prognostic significance of anti-EGFR-related skin toxicity in patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Materials and Methods: We retrospectively analyzed 256 RAS wild-type mCRC patients treated with anti-EGFR monoclonal antibodies at Erciyes University, Kayseri, Turkey (June 2011-February 2024). Survival was estimated using the Kaplan-Meier method with log-rank comparisons. A landmark analysis at 2 months was performed to address guarantee-time bias. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Results: The median PFS was 17 months in patients with grade ≥ 2 skin toxicity versus 8 months in those with grade < 2 skin toxicity (p < 0.001). The median OS was 32 and 21 months, respectively (p < 0.001). In the landmark-adjusted multivariate analysis, grade ≥ 2 skin toxicity was an independent prognostic factor for both PFS (HR 0.52, 95% CI 0.39-0.70, p < 0.001) and OS (HR 0.50, 95% CI 0.37-0.68, p < 0.001). Additional independent factors for OS included albumin, LDH, peritoneal metastasis, age, tumor sidedness, and BMI. The objective response rates were 53.9% and 11.3% in the grade ≥ 2 and grade < 2 groups, respectively (p < 0.001). Conclusions: Grade ≥ 2 skin toxicity was significantly associated with longer PFS, OS, and a higher response rate, and was confirmed as an independent prognostic factor in multivariate analysis. These findings suggest that skin toxicity may serve as a non-invasive marker of treatment efficacy. Prospective studies with time-dependent methodologies are needed to validate these results.