Radiotherapy regimens for rectal cancer: long-term outcomes and health-related quality of life in the Stockholm III trial

BACKGROUND: The Stockholm III trial randomly assigned 840 patients to short-course radiotherapy of 5 × 5 Gy with surgery within 1 week (SRT), short-course radiotherapy of 5 × 5 Gy with surgery after 4–8 weeks (SRT-delay), or long-course radiotherapy of 25 × 2 Gy with surgery after 4–8 weeks (LRT-delay). This study details the long-term oncological outcomes and health-related quality of life (HRQoL). METHODS: Patients with biopsy-proven resectable adenocarcinoma of the rectum were included. Primary outcome was time to local recurrence (LR), and secondary endpoints were distant metastases (DMs), overall survival (OS), recurrence-free survival (RFS), and HRQoL. Patients were analysed in a three-arm randomization and a short-course radiotherapy comparison. RESULTS: From 1998 to 2013, 357, 355, and 128 patients were randomized to the SRT, SRT-delay, and LRT-delay groups respectively. Median follow-up time was 5.7 (range 5.3–7.6) years. Comparing patients in the three-arm randomization, the incidence of LR was three of 129 patients, four of 128, and seven of 128, and DM 31 of 129 patients, 38 of 128, and 38 of 128 in the SRT, SRT-delay, and LRT-delay groups respectively. In the short-course radiotherapy comparison, the incidence of LR was 11 of 357 patients and 13 of 355, and DM 88 of 357 patients and 82 of 355 in the SRT and SRT-delay groups respectively. No comparisons showed statistically significant differences. Median OS was 8.1 (range 6.9–11.2), 10.3 (range 8.2–12.8), and 10.5 (range 7.0–11.3) years after SRT, SRT-delay, and LRT-delay respectively. Median OS was 8.1 (range 7.2–10.0) years after SRT and 10.2 (range 8.5–11.7) years after SRT-delay. There were no statistically significant differences in HRQoL. CONCLUSION: After a follow-up of 5 years, delaying surgery for 4–8 weeks after radiotherapy treatment with 5 × 5 Gy was oncologically safe. Long-term HRQoL was similar among the treatment arms. TRIAL REGISTRATION NUMBER: NTC00904813