Randomized controlled trials of radiation therapy for cutaneous malignancies: a systematic review

In cutaneous oncology, radiotherapy use is largely based on retrospective studies, institutional experience, and expert consensus, with limited high-level evidence to guide practice. We summarize randomized controlled trials in cutaneous radiation oncology and identify gaps in contemporary treatment warranting additional study.

We searched Ovid MEDLINE ALL, Embase.com, and the Cochrane Central Register of Controlled Trials for randomized controlled trials of radiotherapy for cutaneous malignancies: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, and Merkel cell carcinoma. Outcomes of interest included recurrence, survival, toxicity and cosmesis. Study inclusion required approval by three authors, with discrepancies resolved by an additional author.

Thirteen trials entailing fewer than 2500 patients were identified, with only four studies published in the last decade. Three BCC studies compared radiotherapy with other treatments, while two additional BCC studies and one mixed BCC/SCC study compared dose-fractionation regimens. One SCC study evaluated adjuvant radiotherapy versus chemoradiotherapy. Among five melanoma trials, four evaluated adjuvant radiotherapy, including one for the primary tumor site and three for the regional nodal basin, and one compared definitive radiotherapy with topical imiquimod for unresectable melanoma in situ. One Merkel cell carcinoma trial evaluated lymph node basin radiotherapy.

Randomized trials of radiotherapy for cutaneous malignancies are limited, small and heterogeneous, relative to the frequency of these diseases and clinical trials of other therapeutic interventions. Modern randomized trials are needed to bridge these gaps.