Because of the small size of these nonrandomized, retrospective series, the precise benefit from radiation therapy remains unproven.
When recommended, the radiation dose given has been at least 50 Gy to the surgical bed with margins and to the draining regional lymphatics, delivered in 2 Gy fractions. For patients with unresected tumors or tumors with microscopic evidence of spread beyond resected margins, higher doses of 56 Gy to 65 Gy to the primary site have been recommended.[5,10,11,14,15,27,31,35][Level of evidence: 3iiiDiii] These doses have not been studied prospectively in clinical trials.
Local and/or regional control of MCC with radiation alone has been reported in small, highly selected, nonrandomized case series of patients with diverse clinical characteristics.[29,36] Typically, these patients have had inoperable primary tumors and/or nodes or were considered medically inappropriate for surgery.[29,36][Level of evidence: 3iiiDiii]
Retrospective Surveillance, Epidemiology and End Results Program data suggest a survival value for adding radiation to surgery, but the conclusions are complicated by incomplete patient data, no protocol for evaluation and treatment, and potential sampling bias. Prospective randomized clinical trials will be required to assess whether combining surgery with radiation therapy affects survival.[33,34][Level of evidence: 3iiiDiii]
A variety of chemotherapy regimens have been used for patients with MCC in the settings of adjuvant, advanced, and recurrent therapy.[5,34,37,38] [Level of evidence: 3iiiDiii] Even though no phase III clinical trials have been conducted to demonstrate that adjuvant chemotherapy produces improvements in OS, some clinicians recommend its use in most cases because of the following:
- A biologic analogy is made between MCC and the histologically similar small cell carcinoma of the lung, which is considered a systemic disease.
- The risk of metastases and progression with MCC is high.
- Good initial clinical response rates have been noted with some chemotherapy regimens.
When possible, patients should be encouraged to participate in clinical trials.
From 1997 to 2001, the Trans-Tasman Radiation Oncology Group performed a phase II evaluation of 53 MCC patients with high-risk, local-regional disease. High risk was defined as recurrence after initial therapy, involved lymph nodes, primary tumor greater than 1 cm, gross residual disease after surgery, or occult primary with positive nodes. Therapy included local-regional radiation (50 Gy in 25 fractions), synchronous carboplatin (area under the curve [auc] 4.5), and intravenous etoposide (89 mg/m2 on days 1–3 in weeks 1, 4, 7, and 10). Surgery was not standardized for either the primary or the nodes, and 12 patients had close margins, positive margins, or gross residual disease. Twenty-eight patients had undissected nodal beds, and the remainder had a variety of nodal surgeries. With a median follow-up of 48 months, 3-year OS, local-regional control, and distant control were 76%, 75% and 76%, respectively. Radiation reactions in the skin and febrile neutropenia were significant clinical acute toxicities. Given the heterogeneity of the population and the nonstandardized surgery, it is difficult to infer a clear treatment benefit from the chemotherapy.[Level of evidence: 3iiiA]