Prospective evaluation of supplemental external beam radiotherapy with palladium-103 prostate brachytherapy: Long-term results of the 44/20/0 trials

Martin T King; Gregory S Merrick; Robert W Galbreath; Ryan Fiano; Wayne M Butler; Kent E Wallner; Peter F Orio

doi:10.1016/j.prro.2024.10.005

Prospective evaluation of supplemental external beam radiotherapy with palladium-103 prostate brachytherapy: Long-term results of the 44/20/0 trials

Pract Radiat Oncol. 2024 Oct 22:S1879-8500(24)00286-8. doi: 10.1016/j.prro.2024.10.005. Online ahead of print.

Authors

Martin T King¹, Gregory S Merrick², Robert W Galbreath³, Ryan Fiano⁴, Wayne M Butler⁴, Kent E Wallner⁵, Peter F Orio⁶

Affiliations

¹ Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA. Electronic address: [email protected].
² Urologic Research Institute, Sarasota, FL; Bethany College, Bethany, WV, USA.
³ Urologic Research Institute, Sarasota, FL; Ohio University Eastern, St. Clairsville, OH. Electronic address: [email protected].
⁴ Urologic Research Institute, Sarasota, FL.
⁵ Department of Radiation Oncology, University of Washington, Seattle, WA, USA.
⁶ Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA.

PMID: 39447863
DOI: 10.1016/j.prro.2024.10.005

Abstract

Purpose: The 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy impacted 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.

Materials/methods: Both trials enrolled patients with clinical T1c-T2b, Gleason score 7-9 and/or a pre-treatment prostate-specific antigen (PSA) 10-20 ng/ml disease. The 44/20 trial randomized patients to 44Gy EBRT with 90Gy palladium (Pd)-103 versus 20Gy EBRT with 115Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20Gy arm versus monotherapeutic 125Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether 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.

Results: 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 (sub-distribution hazard ratio (sHR) 0.99; 95% CI: 0.43, 2.276; p = 0.97) or the UIR subgroup (sHR 0.72; 95% CI: 0.25, 2.08; p = 0.55). 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 = 0.15) or the UIR subgroup (sHR 0.81; 95% CI: 0.16-4.03; p = 0.80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI: 0.98-1.02; p = 0.88) on multivariate analyses, while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment.

Conclusions: Brachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate risk prostate cancer, including UIR disease.