Real-World Outcomes of Adjuvant Immunotherapy and Radiation Therapy for Stage III Merkel Cell Carcinoma

OBJECTIVES: Immune checkpoint inhibitors demonstrate meaningful promise in advanced unresectable Merkel cell carcinoma (MCC), but their role in the adjuvant setting is evolving. We assessed the association between adjuvant immunotherapy (IO), radiation therapy (RT), or their combination and overall survival (OS) in a real-world cohort. METHODS: Using the National Cancer Database (NCDB), we identified 2538 stage III MCC patients diagnosed between 2017 and 2022 with known adjuvant IO and RT status. Patients were stratified into clinically (n=720) and occult node-positive (n=1818) subgroups. Multivariable logistic regression identified predictors of receipt of adjuvant therapy, while Cox proportional hazards models assessed factors associated with OS. RESULTS: Overall, 25% of patients received neither adjuvant IO nor RT, 6% received both therapies, 5% received IO alone, and 66% received RT alone. Adjuvant IO utilization increased from 4.3% to 13.1% of patients between 2017 and 2022. Receipt of combined IO and RT, as well as RT alone, was associated with improved OS in clinically and occult node-positive patients. Treatment at high-volume centers was associated with improved OS in occult node-positive patients. CONCLUSIONS: In this retrospective cohort, adjuvant IO combined with RT showed the strongest association with improved survival. This OS benefit was particularly pronounced in clinically node-positive patients. These real-world findings complement emerging randomized trial data and suggest that multimodal treatment strategies warrant further investigation in MCC.