High-Risk Features Predict Inferior Survival in Cutaneous Squamous Cell Carcinoma of the Head and Neck
Clinical Summary:
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Design/Population: This secondary analysis of the randomized phase 3 TROG 05.01 trial evaluated prognostic factors in patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with postoperative radiotherapy with or without concurrent chemotherapy.
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Key Outcomes: Patients with extranodal extension and nodal size of at least 22 mm experienced significantly worse disease-free and overall survival than those without these features, identifying a distinct high-risk subgroup following postoperative treatment.
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Clinical Relevance: These findings provide a clinically relevant risk stratification model that may help identify patients most likely to benefit from future studies evaluating adjuvant treatment intensification.
Results from a secondary analysis of the phase 3 TROG 05.01 trial identified a subgroup of patients with high-risk cutaneous squamous cell carcinoma of the head and neck who experienced significantly worse survival 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 disease-free survival is critical to optimize future adjuvant treatment strategies.”
In this study, investigators evaluated data from 321 patients enrolled in the randomized phase 3 TROG 05.01 trial comparing postoperative radiotherapy with or without concurrent chemotherapy. Recursive partitioning analysis using classification and regression trees identified six prognostic nodes and stratified patients into three disease-free survival (DFS) risk groups. The primary end point was DFS. Overall survival (OS) was a key secondary end point.
A high-risk subgroup comprising 88 patients was defined by the presence of extranodal extension and a nodal size of at least 22 mm. The 5-year DFS rate was 56% in the high-risk group compared with 75% among lower-risk patients (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.3 to 3.1; P = .001). Five-year OS was also significantly lower in the high-risk group (59% vs 85%; 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
