Comparative Effectiveness of Different Radical Radiotherapy Treatment Regimens for Prostate Cancer: A Population-Based Cohort Study

BACKGROUND: It is unclear which radiotherapy technique and dose fractionation scheme is most effective in decreasing the risk of prostate cancer death. METHODS: We conducted a population-based cohort study among 15 164 men in the Prostate Cancer database Sweden (version 4.0) treated with primary radical radiotherapy for prostate cancer in Sweden from 1998 to 2016. We calculated hazard ratios with 95% confidence intervals (CIs) of the association between the following exposure groups and outcome: conventionally fractionated external beam radiotherapy (EBRT) to 78 Gy (39 × 2 Gy), EBRT combined with high dose-rate brachytherapy (HDR-BT) (25 × 2 Gy + 2 × 10 Gy), conventionally fractionated EBRT to 70 Gy (35 × 2 Gy), and moderately hypofractionated (M-HF) dose-escalated EBRT (29 × 2.5 Gy or 22 × 3 Gy). RESULTS: Of the men, 7296 received conventionally fractionated EBRT to 78 Gy, 4657 EBRT combined with HDR-BT, 1672 conventionally fractionated EBRT to 70 Gy, and 1539 M-HF EBRT. Using EBRT to 78 Gy as the reference, the multivariable hazard ratios (95% CIs) of prostate cancer death was 0.64 (0.53 to 0.78) for EBRT combined with HDR-BT, 1.00 (0.80 to 1.27) for EBRT to 70 Gy, and 1.51 (0.99 to 2.32) for M-HF EBRT. The multivariable hazard ratios (95% CIs) for death from any cause were 0.79 (0.71 to 0.88), 0.99 (0.87 to 1.14), and 1.12 (0.88 to 1.42), respectively. The lower risk of prostate cancer death comparing EBRT combined with HDR-BT with conventionally fractionated EBRT to 78 Gy was more pronounced for men with high-risk or poorly differentiated tumors. CONCLUSIONS: In this study, EBRT combined with HDR-BT was the most effective radiotherapy treatment regimen, especially for poorly differentiated tumors. Randomized trials comparing EBRT combined with HDR-BT with dose-escalated EBRT should be a priority.