Phase III randomized trial of preoperative concurrent chemoradiotherapy versus preoperative radiotherapy for patients with locally advanced head and neck squamous cell carcinoma

PURPOSE To determine the role of preoperative concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS A total of 222 patients with stage III/IVA-B HNSCC were randomly assigned to receive preoperative concurrent chemoradiotherapy (Pre-S CRT, weekly cisplatin 30mg/m2) or preoperative radiotherapy alone (Pre-S RT). Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS With a medial follow-up of 59 month, the 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) of Pre-S CRT v Pre-S RT group were 53.8% v 39.0% (hazard ratio [HR], 0.74, 95% CI, 0.50 to 1.10, P = 0.13), 53.2% v 38.7%, (HR, 0.69, 95% CI, 0.47 to 1.01, P =0.06), and 80.4% v 68.1% (HR, 0.53, 95% CI, 0.28 to 0.98, P = 0.04), respectively. In patients with larynx-hypopharynx primaries, the 5-year OS, PFS and DMFS of Pre-S CRT v Pre-S RT were 62.7% v 38.8% (HR, 0.59, 95% CI 0.35 to 1.02, P = 0.054), 63.1% v 39.9% (HR, 0.52; 95% CI 0.30 to 0.89, P = 0.03) and 86.2% v 63.3% (HR, 0.35, 95% CI 0.15 to 0.82, P = 0.01), respectively. CONCLUSION The addition of weekly cisplatin concurrent to preoperative RT does not improve OS, but improve DMFS in locally advanced HNSCC. However, in a subset of patients with the larynx-hypopharynx primaries, preoperative chemoradiotherapy has significantly improved PFS and DMFS, and has also provided a borderline benefit in OS in comparison with preoperative radiotherapy alone.