Background: The role of adjuvant radiotherapy for high-risk cutaneous squamous cell carcinomas after surgery with negative margins is unclear. Objective: To conduct a systematic review and meta-analysis examining the risk of poor outcomes for patients treated with surgery alone versus surgery and adjuvant radiotherapy. Methods: A comprehensive search of articles was executed in PubMed, Embase, and the Cochrane Database. Random-effected meta-analyses were conducted. Results: Thirty-three studies comprising 3867 high-risk cutaneous squamous cell carcinomas were included. There were no statistically significant differences in poor outcomes between the surgery only group and surgery with adjuvant radiotherapy group. Estimates for local recurrence for the surgery alone group versus the surgery with adjuvant radiotherapy group were 15.2% (95% confidence interval [CI], 6.3%-27%) versus 8.8% (95% CI, 1.6%-20.9%); for regional metastases, 11.5% (95% CI, 7.2%-16.7%) versus 4.4% (95% CI, 0%-18%); for distant metastases, 2.6% (95% CI, 0.6%-6%) versus 1.7% (95% CI, 0.2%-4.5%); and for disease-specific deaths, 8.2% (95% CI, 1.2%-20.6%) versus 19.7% (95% CI, 3.8%-43.7%), respectively. Limitations: Retrospective nature of most studies with the lack of sufficient patient-specific data. Conclusions: For patients with high-risk cutaneous squamous cell carcinomas treated with margin-negative resection, there were no significant differences in poor outcomes between the surgery only group and the surgery with adjuvant radiotherapy group. Randomized controlled trials are necessary to define the benefit of adjuvant radiotherapy in this setting.
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