Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03.

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.