Timing Matters: Two Divergent Paths in the Multimodal Treatment of Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare but aggressive cutaneous neuroendocrine malignancy with high rates of recurrence and metastasis. Optimal management requires a multidisciplinary approach, including surgery, radiotherapy, and, increasingly, immunotherapy with checkpoint inhibitors. We present a comparative report of two male patients with axillary nodal involvement from MCC who underwent multimodal treatment. The first patient, a 73-year-old male with known primary cutaneous MCC of the forearm, underwent surgical lymphadenectomy followed by postoperative radiotherapy and immunotherapy with Avelumab between February and September 2021, achieving stable disease without progression. The second patient, a 66-year-old male with nodal MCC of unknown primary origin, initially progressed on cisplatin-etoposide chemotherapy. However, early initiation of Avelumab combined with preoperative radiotherapy, followed by surgical lymphadenectomy, resulted in significant tumor regression and a complete pathological response. These cases underscore the crucial importance of integrating early systemic immunotherapy, meticulous radiotherapy planning, and personalized sequencing of multimodal therapies to optimize disease control. The contrasting outcomes emphasize the need for flexible, patient-tailored strategies in the management of Merkel cell carcinoma, particularly in the era of immunotherapy.