TROG 05.01 (chemotherapy added to radiotherapy after surgery for high-risk skin squamous cell carcinoma)

Cutaneous squamous cell carcinoma of the head and neck with involved nodes or aggressive local features is the form of keratinocyte cancer that kills people, and the head and neck oncology habit of adding chemotherapy to postoperative radiotherapy was being carried across to it without evidence. TROG 05.01 randomised 321 patients, 310 of whom started their allocated treatment, to radiotherapy alone or radiotherapy with weekly carboplatin. Seventy-seven per cent had high-risk nodal disease, 19 per cent high-risk primary or in-transit disease and 4 per cent both. The median radiotherapy dose was 60 Gy and 84 per cent of the chemoradiotherapy arm completed six cycles of carboplatin.

At a median follow-up of 60 months, freedom from locoregional relapse at two and five years was 88 and 83 per cent with radiotherapy alone and 89 and 87 per cent with chemoradiotherapy, a hazard ratio of 0.84 (95 per cent confidence interval 0.46 to 1.55, p=0.58). There was no difference in disease-free or overall survival. Carboplatin did not worsen the radiation toxicity, and grade 3 or 4 late toxicity was infrequent in both arms.

Two readings follow. The negative one is that carboplatin adds nothing and should not be given. The positive one is the control arm: surgery followed by radiotherapy controlled 83 per cent of these tumours locally and regionally at five years, and the first site of failure was locoregional rather than distant in all but 7 per cent. That is the benchmark the adjuvant immunotherapy trials had to beat, and it is why C-POST was designed with disease-free survival rather than local control as its endpoint.