Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.

Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.

After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL.

Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021 Jul 01 [Epub ahead of print]

Anthony V D'Amico, Wanling Xie, Elizabeth McMahon, Marian Loffredo, Shana Medeiros, David Joseph, Jim Denham, Parvesh Kumar, Glenn Bubley, Molly Sullivan, Richard Hellwig, Juan Carlos Vera, Rolf Freter, W Jeffrey Baker, Jeffrey Y Wong, Andrew A Renshaw, Philip W Kantoff

Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA., Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA., University of Western Australia, Nedlands, WA, Australia., Calvary Mater New Castle, Waratah, NSW, Australia., University of Missouri School of Medicine, Columbia, MO., Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA., Cape Cod Hospital, Hyannis, MA., St Anne's Hospital, Fall River, MA., Jamaica Plain VA Medical Center, Boston, MA., South Shore Hospital, Weymouth, MA., Hartford Hospital, Hartford, CT., City of Hope National Medical Center, Duarte, CA., Baptist Hospital and Miami Cancer Institute, Miami, FL., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.