Prospective Evaluation of Supplemental External Beam Radiation Therapy With Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44/20/0 Trials.

Abstract

The 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy affected biochemical failure (BF). We report long-term outcomes of both trials and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort. Both trials enrolled patients with clinical T1c to T2b, Gleason scores 7 to 9, and/or a pretreatment prostate-specific antigen (PSA) 10 to 20 ng/mL disease. The 44/20 trial randomized patients to 44 Gy EBRT with 90 Gy palladium (Pd)-103 versus 20 Gy EBRT with 115 Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20 Gy arm versus monotherapeutic 125 Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether the treatment arm was associated with BF for the entire cohort and the unfavorable intermediate-risk (UIR) subgroup. For the combined trial cohort, multivariate Fine-Gray analysis evaluated whether BED was associated with BF while adjusting for clinical factors. There were 247 analyzable patients in the 44/20 trial. At a median follow-up of 13.7 years, there were no differences in BF for the entire cohort (subdistribution hazard ratio [sHR] 0.99; 95% CI, 0.43, 2.276; P = .97) or the UIR subgroup (sHR 0.72; 95% CI, 0.25, 2.08; P = .55). There were 383 analyzable patients in the 20/0 trial. At a median follow-up of 10.4 years, there were no differences in BF for the entire cohort (sHR 0.42; 95% CI, 0.13-1.80; P = .15) or the UIR subgroup (sHR 0.81; 95% CI, 0.16-4.03; P = .80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI, 0.98-1.02; P = .88) on multivariate analyses while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment. Brachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate-risk prostate cancer, including UIR disease.