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

J Am Acad Dermatol. 2025 Mar;92(3):520-527. doi: 10.1016/j.jaad.2024.10.096. Epub 2024 Nov 20.

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.

Keywords: AJCC staging; Merkel cell carcinoma; SEER; prognostication; skin cancer; survival.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Carcinoma, Merkel Cell* / diagnosis
  • Carcinoma, Merkel Cell* / mortality
  • Carcinoma, Merkel Cell* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Risk Assessment / methods
  • Sex Factors
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • United Kingdom / epidemiology
  • United States / epidemiology