Adjuvant Radiation is Associated With Reduced Risks of Local Recurrence and Nodal Metastasis in High-Risk Localized Cutaneous Squamous Cell Carcinoma: A Retrospective Multicenter Cohort Study

Abstract

Purpose: High-risk cutaneous squamous cell carcinomas (HRCSCCs) have an increased likelihood of poor outcomes following surgery. Adjuvant radiation therapy (ART) may decrease this risk; however, there is limited data on its efficacy. The purpose of this study was to evaluate whether ART is associated with reduced risks of local recurrence, locoregional recurrence (LRR), nodal metastasis (NM), and disease-specific death in localized, fully resected HRCSCC.

Methods and materials: A retrospective, multicenter cohort study was conducted. Competing risk modeling was performed to evaluate ART, controlling for patient, tumor, and treatment factors.

Results: This study included 1267 HRCSCC, of which 155 (12.2%) received ART. ART was associated with a 50% reduction in the risk of local recurrence (CHR = 0.47; 95% CI, 0.23-0.96; P = .04), LRR (CHR = 0.47; 95% CI, 0.26-0.83; P = .01), and NM (CHR = 0.45; 95% CI, 0.21-0.98; P = .04). The effect on disease-specific death was small and not statistically significant (CHR = 0.83; 95% CI, 0.35-1.94; P = .66). In modeling, ART decreased the estimated 5-year cumulative incidence of local recurrence from 11.9% (95% CI, 9.4%-14.0%) to 5.9% (2.8%-9.8%), of LRR from 17.8% (15.1%-20.3%) to 9.0% (5.1%-13.6%), and of NM from 9.5% (7.3%-11.2%) to 4.6% (1.7%-8.5%). A subset of HRCSCC at greatest risk of poor outcomes was identified and comprised of tumors that were Brigham and Women's Hospital (BWH) stage T3, BWH stage T2 tumors with 3 risk factors, and/or tumors with lymphovascular invasion. Among these 246 HRCSCC, 74 (30.1%) received ART, and ART was associated with a decreased risk of LRR (CHR = 0.48; 95% CI, 0.26-0.89; P = .02) and NM (CHR = 0.43; 95% CI, 0.19-0.97; P = .04). On modeling, this subgroup experienced greater absolute reductions in the estimated 5-year incidence of LRR from 36.6% (95% CI, 30.0%-45.3%) to 20.0% (11.1%-31.1%) and of NM from 21.1% (17.4%-30.9%) to 9.6% (4.2%-18.1%).

Conclusion: In this retrospective multicenter cohort of HRCSCC, adjuvant radiation was associated with reduced risks of local recurrence and NM. Prospective studies are required to further characterize the effect of adjuvant radiation on HRCSCC.