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

Abstract

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 American Joint Cancer Committee eighth edition staging. (2) To develop a multivariable model for enhanced MCC survival predictions.

Methods

A retrospective analysis of 10,958 histologically confirmed MCC patients between January 2000 and December 2020 was performed. Patient and tumor features were analyzed from 2 cohorts: a US cohort and an external validation UK cohort. A multivariable Fine and Gray competing risk (FG) model was utilized to account for the competing risk.

Results

DSD demonstrated greater discriminatory power as a survival endpoint when compared with OS. Multivariate FG analysis identified the most impactful features of DSD: truncal lesions (subdistribution hazard ratios [SHRs] = 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 the US (C-index 0.75 vs 0.64, P < .001) and external validation UK cohort (C-index 0.77).

Conclusions

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