Identification of a High-Risk Subgroup With Poor Disease-Free Survival After Postoperative Radiotherapy for Cutaneous Squamous Cell Carcinoma

Key Clinical Takeaways: 

• Design/Population: This secondary analysis of the randomized phase 3 TROG 05.01 trial evaluated 321 patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with postoperative radiotherapy with or without concurrent chemotherapy.
• Key Outcomes: A high-risk subgroup defined by extranodal extension and nodal size of 22 mm or greater had significantly worse 5-year disease-free and overall survival compared with patients without these features.
• Clinical Relevance: These findings provide a data-driven approach to identifying patients at highest risk of recurrence after postoperative radiotherapy and support prioritizing this subgroup for future trials of adjuvant treatment intensification.

Results from a secondary analysis of the phase 3 TROG 05.01 trial identified that patients with cutaneous squamous cell carcinoma of the head and neck who display higher risk features experience significantly worse disease-free survival (DFS) following postoperative radiotherapy, with or without concurrent chemotherapy.

“Cutaneous squamous cell carcinoma is a common cancer, and approximately 5% of cases present with high-risk features, such as regional nodal metastases,” stated Sandro Virgilio Porceddu, MD, University of Melbourne, Australia, and coauthors. “Identification of patients with poor [DFS] is critical to optimize future adjuvant treatment strategies.”

In this study, data were collected from 321 patients randomized to receive postoperative radiotherapy with or without concurrent chemotherapy. Recursive partitioning analysis using classification and regression trees identified 6 nodes and stratified patients into 3 disease-free survival (DFS) risk categories. A high-risk group (n = 88) was defined by the presence of extranodal extension and a nodal size of 22 mm or greater. The primary end point was DFS, and a key secondary end point was overall survival (OS).

At analysis, the 5-year DFS rate was 56% in the high-risk group compared with 75% in the lower-risk group (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.3 to 3.1; P = .001). The corresponding 5-year OS rates were 59% and 85%, respectively (HR, 3.2; 95% CI, 1.9 to 5.3; P <.001).

“The results of this secondary analysis suggest that patients with extranodal extension and a nodal size of 22 mm or greater represent a high-risk subgroup with inferior DFS following [postoperative radiotherapy] with or without concurrent chemotherapy,” concluded Dr Porceddu et al. “These patients may benefit from future trials that evaluate adjuvant treatment intensification.”

Source: 

Porceddu VS, Connolly E, Bressel M, et al. Prognostic subgroups for disease-free survival with cutaneous squamous cell carcinoma of the head and neck. JAMA Otolaryngol Head Neck Surg. Published online: August 28, 2025. doi:10.1001/jamaoto.2025.2110