Adjuvant local irradiation for Merkel cell carcinoma.

Objectives: To determine the effect of adjuvant local irradiation on (1) disease recurrence and (2) survival rates in Merkel cell carcinoma (MCC).

Data Sources: An Ovid MEDLINE search (January 1966-May 26, 2004) was performed using the following criteria: group 1, "Merkel cell OR trabecular OR neuroendocrine skin OR APUDoma skin OR primary small cell skin OR primary undifferentiated skin OR endocrine skin OR neuroepithelial" AND group 2, "carcinoma OR tumor OR cancer" with mapping modifiers "-title, -abstract, -keyword, -subject heading." The search yielded 843 citations.

Study Selection: The Ovid set was then searched using the following criteria: "surgery OR radiation OR radiotherapy," which yielded 242 discrete citations. Reports from all 242 citations were reviewed. For the remaining 601 citations, abstracts (when available) were reviewed to assess the level of relevance for potential inclusion; reports from 63 of these citations were reviewed. An additional 28 secondary references were reviewed, for a total of 333 reports.

Data Extraction: The following criteria for inclusion were applied to each potential patient: (1) a histopathologic diagnosis of MCC; (2) a single, primary tumor arising on the skin, for which (3) the primary treatment was surgical excision (local excision, wide excision, or Mohs surgery) with or without the use of adjuvant irradiation (to the tumor bed); (4) following surgery, negative (clear) surgical margins were obtained; (5) during the postoperative follow-up period, disease recurrence, progression, and survival and/or duration of event-free interval was documented with (6) a minimum follow-up of 1 month. A total of 1254 patients were included in the analysis.

Results: Statistically significant reductions in local (hazard ratio [HR], 0.27; P < .001) and regional (HR, 0.34; P < .001) recurrence were observed among patients treated with combination therapy compared with surgery alone. Similar rates of distant metastasis were observed between treatment groups (HR, 0.79; P = .31). Overall survival rates were 87% (1 year) and 49% (5 years). Cause-specific survival rates were 90% (1 year) and 62% (5 year). In general, differences in overall (HR, 0.78; P = .16) and cause-specific (due to MCC: HR, 0.72; P = .14) survival rates between treatment groups did not reach statistical significance. A subgroup analysis that excluded single-patient case reports and studies of only 1 treatment group revealed a significant overall (HR, 0.63; P = .02) and cause-specific (HR, 0.62; P = .04) survival advantage after treatment with combination therapy.

Conclusions: Surgery plus local adjuvant irradiation was associated with significantly lower rates of local and regional recurrence of MCC than surgery alone. Prospective investigation is needed to clarify the presence of a survival benefit from combination therapy.