Is the Addition of Chemotherapy to Adjuvant Radiation in Merkel Cell Cancer Beneficial? Real-World Data with Long-Term Follow-Up.

BACKGROUND

The role of adding chemotherapy to adjuvant radiation therapy in resectable Merkel cell carcinoma (MCC) remains controversial. Previous studies have shown conflicting results, and long-term outcome data are limited.

OBJECTIVES

In this study, we aimed to evaluate the long-term survival outcomes of patients with resectable MCC treated with surgery followed by either radiation alone or combined chemoradiation.

METHODS

This retrospective multicenter cohort study analyzed 105 patients with resectable MCC treated between 1985 and 2023. Patients received either adjuvant radiation alone ( = 53) or chemoradiation ( = 52) following surgery. The primary endpoints were overall survival and disease-free survival. The secondary endpoints included an analysis of prognostic factors and treatment-related characteristics. The median follow-up was 12 years.

RESULTS

The 20-year overall survival rates were 53.4% for chemoradiation versus 30.7% for radiation alone ( = 0.324). Median survival in the chemoradiation groups was not reached during the follow-up period; in the radiation group, it was 8.8 years. Likewise, the twenty-year disease-free survival rates were not significantly different between the chemoradiation and radiation groups: 47% vs. 29.3%, respectively, = 0.495. The chemoradiation group had significantly more advanced disease (88% vs. 28.3% stage III) but was younger (median 65.9 vs. 77.3 years, = 0.002) and received higher radiation doses (median 50 Gy vs. 45 Gy, = 0.002). After controlling for age, stage, and tumor location in a multivariable analysis, the survival differences were still not significantly different (hazard ratio (HR) = 1.36, 95% CI 0.61-3.00, = 0.450).

CONCLUSIONS

While the multivariate analysis did not indicate a survival advantage to adding chemotherapy to radiation, the comparable survival outcomes despite significantly more advanced disease in the chemoradiation group suggest a possible benefit in high-risk patients. Our results indicate the need for prospective studies with larger, stage-matched cohorts to definitively establish the role of adjuvant chemotherapy in high-risk resectable MCC.