A multivariable disease specific model enhances prognostication beyond current Merkel cell carcinoma staging: an international cohort study of 10,958 patients.

Background: Merkel cell carcinoma (MCC) is a highly aggressive cutaneous malignancy for which accurate prognostication is necessary to support clinical management.

Objective: 1. To determine which survival endpoint - disease-specific-death (DSD) or overall survival (OS)- was better stratified by MCC AJCC 8^th edition staging. 2. To develop a multivariable model for enhanced MCC survival predictions.

Methods: Retrospective analysis of 10,958 histologically confirmed MCC between January 2000 and December 2020 was performed. Patient and tumor features were analysed from two cohorts: a US cohort and an external validation UK cohort. A multivariable Fine and Gray Competing Risk (FG) model was utilised to account for competing risk.

Results: DSD demonstrated greater discriminatory power as a survival endpoint when compared to OS. Multivariate FG analysis identified the most impactful features for DSD: truncal lesions (subdistribution hazard ratios (SHR) 1.96, p<.001), age >84 years (SHR 1.79, p<.001), male sex (SHR 1.34, p<.001) and marital status (SHR 1.09, p<.001). A second FG model incorporating those impactful features enhanced survival predictions beyond current MCC staging criteria alone in both US (C-index 0.75 vs 0.64, p<.001) and external validation cohorts. cohort (C-index 0.77).

Conclusions: MCC staging can stratify DSD better than OS. Additional patient and tumour features enhanced prognostication beyond current staging systems.