Review
Merkel cell carcinoma adjuvant therapy: Current data support radiation but not chemotherapy

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Merkel cell carcinoma (MCC) 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. After excision of detectable cancer, optimal adjuvant therapy is not well established. A role for adjuvant radiotherapy is increasingly supported by observational data. These data suggest that a regimen of surgery plus adjuvant radiotherapy is associated with both a lower loco-regional recurrence rate and longer overall survival when compared with surgery alone. 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 MCC: lack of evidence for improved survival; the associated morbidity and mortality; important differences between small-cell lung cancer and MCC; 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 MCC. Taken together, these arguments suggest that adjuvant radiation may be indicated for many MCC patients while adjuvant chemotherapy should largely be restricted to clinical trials.

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Data support adjuvant radiotherapy for MCC

Adjuvant radiotherapy is associated with a marked decrease in local recurrences and a trend to improved survival in multiple retrospective studies. A meta-analysis was carried out on 1254 patients with MCC 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 were included regarding recurrence and survival.5 In this study, patients who received adjuvant radiation therapy

Adjuvant chemotherapy for MCC is not currently supported by data

Many patients with MCC receive adjuvant chemotherapy in analogy to a more common neuroendocrine tumor, small-cell carcinoma of the lung (SCLC). However, there are several important differences between SCLC and MCC that suggest that therapy established for one disease should not automatically be extended to the other. Below are 6 issues that raise concern about the routine use of adjuvant chemotherapy in MCC.

1. Adjuvant chemotherapy for MCC has not been shown to improve survival. Several recent

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Supported by Harvard/National Cancer Institute Skin Cancer Specialized Program of Research Excellence (SPORE), Merkel cell carcinoma patient fund, National Institutes of Health K02-AR050993.

Conflicts of interest: None declared.

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