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Radiation versus resection for Merkel cell carcinoma

The rising incidence of Merkel cell carcinoma (MCC) has heightened awareness and interest in this rare and aggressive form of skin cancer. Approximately 25% of patients diagnosed withMCC have clinically apparent lymph node involvement or metastatic disease at the time of initial presentation and an additional 23% to 32% are found to have microscopic regional lymph node metastases with further evaluation. The stage of disease at presentation appears to be prognostic; however, optimal treatment strategies are still heavily debated. In this issue of Cancer, Fang et al report their outcomes in patients withMCC and regional lymph node metastases. Because MCC is a radiosensitive tumor, 1 of the major controversies is whether surgical resection or radiotherapy (RT) represents the optimal treatment for MCC patients with regional spread of disease. Fang et al compared patients treated with either lymph node radiation monotherapy or completion lymph node dissection (CLND) with or without RT. Another highly controversial issue, the role of systemic chemotherapy for this disease, is outside the realm of this report. From a data repository at the Fred Hutchinson Cancer Research Center, 86 patients with regional lymph node metastases at presentation were identified. Fifty patients met the inclusion criteria of pathologically confirmed regional lymph node involvement, adequate follow-up after regional therapy, and lack of distant metastasis. Lymph node involvement was classified as either clinically palpable or microscopically detected by sentinel lymph node biopsy (SLNB). Patients were seen either for treatment or for consultation only, with treatments rendered elsewhere. The authors conclude that lymph node basin RT provides regional control and survival rates that are comparable to CLND, regardless of tumor burden. The authors describe the treatment and outcome of 2 distinct patient populations: those with microscopic tumor burden in the regional lymph node basin detected by SLNB, and those with clinically apparent lymph node disease. None of the patients with microscopic lymph node disease detected on SLNB developed regional disease recurrence regardless of the treatment modality. However, the excellent regional control rate is most likely due to the early detection of minimal tumor burden and not choice of treatment. In fact, it may even be reasonable to postulate that selective lymphadenectomy itself is therapeutic if the only focus of metastatic disease is removed during the diagnostic procedure, and that both CLND and RT represent adjuvant therapies. The authors’ conclusion that CLND and RT are equally effective in this group of patients with micrometastatic disease is further confounded by the finding that greater than half of the patients who underwent CLND subsequently underwent adjuvant RT as well. The second distinct patient population described includes patients who presented with clinically apparent lymph node disease. Drawing meaningful conclusions from this cohort of patients is challenging. Among 24 patients with palpable lymph nodes, only 6 were truly treated with radiation monotherapy because excision of the clinically apparent lymph node essentially changes the lymph node status from macroscopic to microscopic (or nil) disease. The authors observed a total of 5 patients with regional disease recurrences in this group with clinically apparent disease. Although these are extremely small numbers, 3 patients with palpable lymphadenopathy who underwent CLND alone did not develop