Merkel cell carcinoma is a skin cancer with 30% mortality and an incidence that has tripled in the past 15 years. There is agreement that surgical excision with negative margins is an appropriate therapeutic first step and that sentinel lymph node biopsy is a powerful prognostic indicator. Following excision of detectable cancer, optimal adjuvant therapy is not well established. A role for adjuvant radiotherapy is increasingly supported by retrospective data suggesting a nearly four-fold decrease in local recurrences if radiation is added to surgery. In contrast, a role for adjuvant chemotherapy is not well supported. The rationale for chemotherapy in this disease is based on small-cell lung cancer, a more common neuroendocrine tumor for which chemotherapy is the primary treatment modality. Several issues call into question the routine use of adjuvant chemotherapy in Merkel cell carcinoma: lack of evidence for improved survival; the associated morbidity and mortality; important differences between small-cell lung cancer and Merkel cell carcinoma; and rapid development of resistance to chemotherapy. Importantly, chemotherapy suppresses immune function that plays an unusually large role in defending the host from the development and progression of Merkel cell carcinoma. Taken together, these arguments suggest that adjuvant chemotherapy for Merkel cell carcinoma patients should largely be restricted to clinical trials.

Merkel cell carcinoma is a neuroendocrine cancer that typically presents as a rapidly growing non-specific nodule on sun exposed skin in people over 65 years of age. The recent increase in incidence to over 1000 cases a year in the United States has led Merkel cell carcinoma to become the second most common cause of non-melanoma skin cancer death.^1,2 Optimal management for Merkel cell carcinoma beyond surgical excision is not agreed on, and no randomized trials have been carried out. Sentinel lymph node biopsy has been shown to be powerful in predicting subsequent recurrences as well as in determining if further nodal treatment is indicated.^3,4

Adjuvant radiotherapy is associated with a marked decrease in local recurrences and a trend to improved survival in multiple retrospective studies. Although no prospective trials of radiation therapy have been performed, many retrospective studies find that adjuvant radiotherapy is associated with better outcomes in MCC. A meta-analysis was carried out on 1254 Merkel cell carcinoma patients previously reported in the literature who met the following criteria: a single primary tumor arising on skin that was excised with negative surgical margins on whom follow-up data was included regarding recurrence and survival.⁵ In this study, patients who received adjuvant radiation therapy had improved outcomes compared to those who received surgical excision only. Specifically, local recurrences at 5 years were three times less likely (12% vs 39%, p < .001) if adjuvant radiation was given, and a similar association was found for regional recurrences (23% vs 56%, p < .001) (see Figure 1). Patients who received adjuvant radiation also had an improved overall and cause specific survival, although this was not statistically significant. In a subgroup analysis excluding single-patient case reports and non-comparative studies there was a significant cause-specific survival advantage associated with adjuvant radiation to the local site (hazard ratio for death = 0.62, p = 0.04). Although one large single institution study did not find a statistically significant improvement in outcomes if radiation therapy was given, only 13% of patients in this study received adjuvant radiation and those that received surgery mono-therapy had exceptional results with only 8% experiencing local recurrences.⁴ Although retrospective and not randomized, in aggregate these studies strongly suggest improved outcomes in Merkel cell carcinoma with the addition of adjuvant radiation therapy.