Table 3 Summary of urological cancer practice-defining RT clinical trials

From: Practice-changing radiation therapy trials for the treatment of cancer: where are we 150 years after the birth of Marie Curie?

Trial name (first author) Trial methodology Practice-defining trial results and methods Publications of trial results Publications related to trial conduct Evidence of practice change
Prostate
 PR-07 (Mason) Androgen deprivation therapy (ADT) alone vs. ADT + RT in men with T3-4N0M0 prostate cancer, or T1-2 disease with PSA > 40 or PSA 20–40 with Gleason score 8–10. Randomised 1205 patients. Overall survival significantly improved by the addition of RT. 69 NA UK: NICE.179
 SPCG-7 (Widmark) ADT alone vs. ADT + RT. Randomised 875 patients. Addition of RT improved overall survival and prostate cancer specific mortality. 68 NA UK: NICE.179
 MRC RT-01 (Dearnaley) Radical RT 64 Gy in 32 fractions vs. 74 Gy in 37 fractions. Randomised 843 patients. Significantly improved biochemical progression-free survival in the 74 Gy dose group, but no improvement in overall survival. 72, 73 180 International: NCCN.181 UK: NICE.179
 Dutch (Peeters) 78 Gy vs. 68 Gy in patients with T1-4 prostate cancer with PSA < 60. Randomised 669 patients. Significantly improved biochemical progression-free survival for 78 Gy but no effect on overall survival. Higher rates of acute and late GI and GU toxicity for 78 Gy group. 71, 182 NA International: NCCN.181 UK: NICE.179
 RTOG 0415 (Lee) 73.8 Gy in 41 fractions vs. a hypofractionated regime 70 Gy in 28 fractions for men with low-risk prostate cancer. Randomised 1092 patients. Hypofractionated regime non-inferior to conventional fractionation, but resulted in significantly increased late grade 2/3 GI and GU toxicity. 80 NA NA
 HYPRO (Aluwini) Hypofractionated RT of 64·6 Gy in 19 fractions, three fractions per week vs. 78 Gy in 39 fractions, five fractions per week, in men with intermediate-high-risk prostate cancer. Randomised 804 patients. Hypofractionated regime was not superior to the conventionally fractionated regime in terms of 5-year relapse-free survival, with higher incidence of acute GI toxicity, late GI and late GU toxicity. 79, 183, 184 NA NA
 CHHiP (Dearnaley) 60 Gy in 20 fractions OR 57 Gy in 19 fractions) vs. standard dose 74 Gy in 37 fractions for radical treatment of T1-3aN0M0 prostate cancer with PSA < 30. Randomised 3216 patients. 60 Gy in 20 fractions over 4 weeks non-inferior to conventionally fractionated radiotherapy, with similar rates of toxicity. Dose constraints designed for the CHHiP trial adopted in other trials. Supported implementation of IMRT for prostate cancer treatment. 75, 76 NA International: AUA/ASTRO/SUO: guideline.185 German Society of Radiation Oncology guideline.186 UK: RCR dose fractionation guideline.77
 PROFIT (Catton) 78 Gy in 39 fractions vs. hypofractionated RT of 60 Gy in 20 fractions over 4 weeks, with both arms receiving no ADT. Randomised 1206 men. Non-inferior biochemical-clinical failure for hypofractionation with no increase in grade 3 or higher late GI or GU toxicity. 81 NA International: AUA/ASTRO/SUO: guideline.185 German Society of Radiation Oncology guideline.186 UK: RCR dose fractionation guideline.77
 ALSYMPCA (Parker) Radium-223 vs. placebo in men with castration-resistant prostate cancer and bone metastases, given 4 weekly for a total of 6 injections. Randomised 921 patients in a 2:1 ratio. Improved overall survival for radium-223, with longer time to first symptomatic skeletal related event and improved quality of life scores in the radium group. 82, 83, 187 NA International: ESMO.84 NCCN.181 UK: NICE.85
Bladder
 BC2001 (James) ChemoRT (5FU/mitomycin C) vs. RT alone; patients also randomised to receive whole-bladder or modified volume RT. Randomised 360 patients. Improved locoregional control of bladder cancer with chemoRT, without a significant increase in adverse events. Dose constraints derived from BC2001 data used in IDEAL, HYBRID and RAIDER studies. 86, 188 189 UK: NICE.88
 BCON (Hoskin) RT alone vs. RT plus carbogen-nicotinamide (CON) in locally advanced bladder cancer. Randomised 333 patients. Overall survival significantly improved with the addition of CON. 87 NA UK: NICE.88
  1. AUA/ASTRO/SUO American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology, ESMO European Society for Medical Oncology, NCCN National Comprehensive Cancer Network, NICE National Institute for Health and Care Excellence, RCR Royal College of Radiologists