Health-related quality of life comparing standard and prolonged time-to-surgery after neoadjuvant chemoradiotherapy for esophageal cancer: results from the multicenter, randomized, controlled NeoRes II trial

Standard time-to-surgery after neoadjuvant chemoradiotherapy for esophageal cancer has historically been 4–6 weeks. Observational studies have suggested improved oncological outcomes and health-related quality of life in patients after prolonged time-to-surgery. This study aimed to investigate whether prolonged time-to-surgery is associated with improved health-related quality of life compared to the standard interval. This study is a secondary endpoint analysis within the NeoRes II trial, in which patients with locally advanced resectable esophageal cancer were randomized to either standard time-to-surgery (4–6 weeks) or prolonged time-to-surgery (10–12 weeks). The primary endpoints have been reported previously. Health-related quality of life was assessed using the EORTC QLQ-C30 and QLQ-OG25 questionnaires at time of diagnosis, preoperatively, and at 6-months and 1–5 years postoperatively. A total of 249 patients were randomized of whom 192 were available for health-related quality of life analyses, with 97 (51%) assigned to standard time-to-surgery and 95 (49%) to prolonged time-to-surgery. The groups were well-matched regarding baseline characteristics. Preoperatively, within a week of the day of surgery, patients in the prolonged time-to-surgery group reported better global quality of life, improved physical functioning, and less fatigue, coughing, dysphagia, odynophagia, pain, discomfort, and weight loss compared to those in the standard time-to-surgery group. These benefits were observed at 6 months postoperatively, but not thereafter during follow-up, where no significant differences were observed. Although prolonged time-to-surgery was associated with better preoperative health-related quality of life, no such benefits were observed postoperatively. In addition, the results from the primary endpoint analysis suggested that longer time-to-surgery was associated with worse oncological outcomes. This, together with the results of the current sub-study, strongly supports that the standard time-to-surgery of 4–6 weeks should be recommended after neoadjuvant chemoradiotherapy for esophageal cancer.