Development and internal validation of the CLIP-M score for advanced mucosal malignant melanoma: exploratory prognostic stratification and comparative assessment with the RMH score

BACKGROUND: Mucosal malignant melanoma (MMM) is a rare, aggressive malignancy with poor prognosis in the advanced setting. Although the Royal Marsden Hospital (RMH) score is widely used in advanced malignancies, its utility in advanced MMM remains insufficiently characterized. We aimed to develop a composite prognostic score and compare its performance with RMH. METHODS: We analyzed 80 patients with advanced MMM (metastatic or unresectable) from a multicenter database. Pretreatment inflammatory indices and clinical variables were evaluated. The CLIP-M score (Clinical and Inflammatory Prognostic Score in Mucosal Melanoma) was derived from independent predictors in multivariable Cox regression and internally validated by bootstrap resampling. Predictive accuracy was compared with RMH using time-dependent AUCs, Harrell's C-index, and Kaplan-Meier estimates. RESULTS: During a median follow-up of 65.2 months, 63 deaths occurred. SII was selected as the biological component. CLIP-M integrated high SII (≥ 789; derived by 12-month time-dependent ROC analysis), age ≥ 65 years, and non-head & neck primary location. Time-dependent AUCs numerically favored CLIP-M over RMH at 12 months (0.731 vs. 0.613), 24 months (0.824 vs. 0.680), and 36 months (0.863 vs. 0.697), with a nominal 36-month between-model difference that did not remain significant after correction for three time horizons (ΔAUC = 0.166; nominal p = 0.039). Bootstrap internal validation showed moderate discrimination, with apparent and optimism-corrected C-indices of 0.648, and acceptable 12-month calibration. CLIP-M stratified patients into low-risk (score 0-1) and high-risk (score 2-3) groups with divergent median overall survival (24.8 vs. 6.4 months; HR 4.03, 95% CI 2.25-7.22; p < 0.001). CONCLUSION: CLIP-M provided exploratory, clinically interpretable risk stratification in advanced MMM and showed numerically higher discrimination than RMH; however, optimism-corrected performance was moderate and external validation is required before clinical implementation.