Bladder control.

Top Line: Conventional fractionation (2 Gy x 32 = 64 Gy) and hypofractionation (2.75 Gy x 20 = 55 Gy) are both “reasonable” options per NCCN for definitive radiation of locally-advanced bladder cancer.

The Study: So which is better? Beyond the obvious benefit of 2.5 fewer weeks of daily treatments with HFX, the two have never been compared head-to-head in a prospective manner. And they still haven’t. But we do have a meta-analysis comparing outcomes when each is done prospectively on two separate randomized trials. In both trials, every patient received definitive radiation with either CFX or HFX used per physician preference. Note that randomized treatments were done in addition to radiation: +/- mitomycin / 5FU in one and +/- niacinamide / carbogen in the other. The meta-analysis had two primary endpoints. The first was locoregional control, and HFX would be deemed non-inferior with a hazard ratio [HR] ≤ 1·25. The second was late bladder or rectum toxicity, with HFX deemed non-inferior if the absolute risk difference was  ≤ 10%. There was a nice split in radiation regimens across all patients in both trials with 376 (48%) receiving CFX and 406 (52%) receiving HFX. Far from non-inferior, HFX was statistically superior in regards to locoregional control with a HR of 0.71 (95% CI 0.52–0.96). Furthermore, toxicity was similar with HFX having a -3.72% (−11.85 to 5.10) absolute decrease in toxicity.

TBL: “There is a cogent argument for 55 Gy in 20 fractions being adopted as the standard of care in this patient group.” | Choudhury, Lancet Oncol 2021