Predicting Benefit of Adjuvant Radiation Therapy for Cutaneous Squamous Cell Carcinoma: A Systematic Review

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer, and its incidence has been rising. Certain patients with high-risk cSCC may benefit from adjuvant radiation therapy (ART). This systematic review aims to analyze existing data on factors of cSCC that predict benefit from ART and explore approaches to optimize patient outcomes.

A systematic review was performed. The terms "cutaneous squamous cell carcinoma," "adjuvant radiation therapy," "clinical recommendations," and "predicting benefit," along with Boolean terms "AND" and "OR" were used to search PubMed, Scopus, Embase, and Google Scholar. Original articles published before April 2025 were screened for relevance.

Although it is well established that adjuvant radiation therapy (ART) provides significant benefit when directed to the appropriate high-risk patients, there are limited studies reporting clinicopathologic factors that can reliably inform which patients are most likely to benefit from ART. As such, decisions for ART usage based on clinicopathologic factors are variable. The 40-GEP test has been shown to accurately identify which patients would benefit most from ART (Class 2B), and to aid in determining which patients can consider deferring ART (Class 1). The Class 2B result is the only high-risk factor that has been demonstrated to predict benefit from ART.

Relying exclusively on clinicopathologic factors has limitations, contributing to inconsistent use of ART in clinical settings. This systematic review highlights that the 40-GEP test improves risk stratification in cSCC and aids in making more precise ART decisions, including determining which patients may safely defer treatment.