Background
Phase III randomized controlled trial (Trans-Tasman Radiation Oncology Group TROG 05.01) evaluating postoperative chemoradiotherapy vs postoperative radiotherapy alone in high-risk cutaneous squamous cell carcinoma (cSCC) of the head and neck. 321 patients with completely resected high-risk cSCC H&N (parotid and/or cervical node involvement, or T4 primary, or perineural invasion of named nerve). Post-op RT 60 Gy in 30 fractions ± concurrent carboplatin.
Interventions and follow up
Arm A: Postoperative CRT — RT 60 Gy in 30 fractions + concurrent weekly carboplatin AUC 2
Arm B: Postoperative RT alone — 60 Gy in 30 fractio
Primary endpoint: 2-year locoregional relapse-free survival
mFollow up: Median 60 month
Arm B: Postoperative RT alone — 60 Gy in 30 fractio
Primary endpoint: 2-year locoregional relapse-free survival
mFollow up: Median 60 month
Results
2-Year LR (CRT vs RT): 86% vs 79% (P=.08 — not significant primary endpoint)
5-Year OS: No significant difference between arms
Subgroup with parotid involvement: Trend toward benefit with CRT, but not statistically significant
Grade ≥3 toxicity: CRT arm higher (mucositis, hematologic)
5-Year OS: No significant difference between arms
Subgroup with parotid involvement: Trend toward benefit with CRT, but not statistically significant
Grade ≥3 toxicity: CRT arm higher (mucositis, hematologic)
Adverse events
Main adverse events: CRT arm: grade ≥3 mucositis 36% vs 18% (RT alone); grade ≥3 hematologic toxicity higher; weight loss and feeding tube placement more frequent. RT alone well tolerated with acceptable late skin/fibrosis.
Conclusions
Adding concurrent carboplatin to postoperative RT did not significantly improve locoregional relapse-free survival in high-risk cSCC of the H&N, though a non-significant trend favored CRT (86% vs 79% at 2 years). The trial was not powered to detect a modest benefit; results inconclusive for routine use of concurrent chemotherapy.
Key Limitations
Key Limitations: May have been underpowered to detect a moderate improvement; carboplatin is a less potent radiosensitizer than cisplatin; heterogeneous high-risk population (parotid, neck nodes, perineural invasion); evolving systemic options (immunotherapy) not available at trial design.
Clinical Context
Despite a non-significant primary endpoint, this is the largest RCT in postoperative cSCC H&N and provides the best available evidence for this setting. Most centers continue to offer postoperative RT alone as standard for high-risk cSCC. Addition of chemotherapy remains controversial; cisplatin-based CRT (by analogy with mucosal H&N SCC) is considered at select centers for very-high-risk features. Immunotherapy (cemiplimab) is emerging as an option in the unresectable/metastatic setting.