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 (n = 53) or chemoradiation (n = 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 (p = 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, p = 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, p = 0.002) and received higher radiation doses (median 50 Gy vs. 45 Gy, p = 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, p = 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.