MCC staging system stratifies disease-specific death better than overall survival

Key takeaways:

• The authors posit the Fine and Gray (FG) Competing Risk model may be a welcome addition to the current staging methods.
• The FG model found additional factors to drive disease specific death.

The American Joint Committee on Cancer eighth edition staging system for Merkel cell carcinoma can risk-stratify disease-specific death better than overall survival with room for improvement, according to a study.

As a rare and highly aggressive form of skin cancer, Merkel cell carcinoma (MCC) affects elderly patients more commonly than younger patients. Unfortunately, the prognostication for MCC is currently unclear, putting this population at risk for serious health outcomes and death.

“Prognostication using [the American Joint Committee on cancer (AJCC) eighth edition staging system] is currently limited by its dependence on estimated overall survival (OS) rather than disease-specific death (DSD), endpoints which account for the high rate of competing risks in elderly MCC populations,” Tom W. Andrew, MBChB, MSc, of the Translation and Clinical Research Institute at Newcastle University and the department of plastic and reconstructive surgery at Royal Victoria Infirmary, and colleagues wrote.

In this retrospective study, the authors set out to determine if AJCC eighth edition staging was better at stratifying OS or DSD as a survival endpoint among patients with MCC. They pulled data on 10,958 histologically-confirmed MCC cases from the U.S. cohort of the NIH Surveillance, Epidemiology and End Results database and 30 U.K. National Health Service hospitals for analysis.

Results showed that the AJCC eighth edition staging was a better predictor of DSD than OS (concordance index, 0.65 vs. 0.58; P < .001) according to findings from a multivariable Fine and Gray (FG) Competing Risk model.

The study stated that AJCC staging stratified survival probabilities into four distinct prognostic groups using DSD endpoints, but failed to stratify survival probabilities between certain stage groups using OS endpoints.

According to the authors, the FG model was better at identifying risk among MCC patients as it combined the AJCC staging method and non-staging features. For example, the model found that driving factors for DSD were truncal vs. upper limb lesions (subdistribution HR [SHR] = 1.96; 95% CI, 1.53-2.18), being aged older than 84 years vs. younger than 64 years (SHR = 1.79; 95% CI, 1.61-2.01), male vs. female sex (SHR = 1.32; 95% CI, 1.2-1.41), unmarried vs. married status (SHR = 1.09; 95% CI, 1.01-1.19) and tumor invasion beyond subcutis vs. confined to dermis (SHR = 2.34; 95% CI, 1.83-2.85) — factors that are not included in AJCC staging.

“MCC AJCC pathological staging criteria can risk-stratify DSD better than OS,” the authors concluded. “The additional non-staging features identified in this study should be considered in future research as we approach the next update of MCC AJCC staging.”