Adding Docetaxel to ADT/Radiation Therapy Does Not Improve Survival in Non-Metastatic Unfavorable-Risk Prostate Cancer But May Benefit Some Subgroups

The addition of docetaxel did not improve overall survival for patients with nonmetastatic unfavorable-risk prostate cancer, although it reduced incidence rates of radiation therapy-induced cancer.

Although the addition of docetaxel to androgen deprivation therapy (ADT) and radiation therapy did not prolong survival for patients with nonmetastatic unfavorable-risk prostate cancer, the combination reduced the incidence of radiotherapy–induced cancer and may prolong survival in those with prostate-specific antigen (PSA) of less than 4 ng/mL, according to results from a phase 3 randomized trial (NCT00116142) published in the Journal of Clinical Oncology.

After a median follow-up of 10.2 years (IQR, 8.00-11.40), 89 patients died, including 44 in the docetaxel arm and 45 in the ADT plus radiotherapy arm. Moreover, 42 of the deaths were attributed to the prostate cancer. Although overall survival (OS) benefit initially seemed higher in the docetaxel arm, the curves merged with further follow up (HR, 0.99; 95% CI, 0.65-1.51; P = .98). For patients in the docetaxel arm, 10-year estimates for survival were 72% (95% CI, 63%-79%) in the docetaxel arm compared with 74% (95% CI, 66%-80%) for patients in the ADT plus radiotherapy arm. Restricted mean survival time (RMST) over a 10-year period was observed at 9.11 years and 8.82 years for patients in the docetaxel and ADT plus radiotherapy arms, respectively, including a difference of 0.29 (95% CI, -0.19-0.76; P = .22).

“Among men randomly assigned to receive ADT + [radiotherapy] + docetaxel versus ADT + [radiotherapy], significantly less [radiotherapy]–induced cancers were observed,” the investigators wrote. “The treatment effect of adding docetaxel to ADT + [radiotherapy] on [OS] in men with a PSA [of less than] 4 ng/mL was driven by the absence of [prostate cancer] death, providing evidence to support a distinct biology in low [prostate-specific antigen] (PSA)-producing, unfavorable-risk PC that is docetaxel-sensitive.”

Eligible patients needed to have histologically confirmed prostate adenocarcinoma. The primary end point of the study was OS, with key secondary end points including prostate cancer-specific mortality (PCSM), metastasis-free survival (MFS), and PSA recurrence-free survival (PSA RFS).

A total of 350 men were enrolled between September 21, 2005, and January 13, 2015 and were randomized 1:1 to receive treatment with either ADT plus radiotherapy for 6 months (n = 175) or ADT plus radiotherapy for 6 months plus 10 cycles of docetaxel (n = 175). Patients in the control group were treated with 1.8 Gy of radiotherapy for 39 treatments plus a luteinizing hormone releasing hormone agonist and antiandrogen starting 2 months prior to radiotherapy and ending 2 months after radiotherapy. Those in the experimental cohort received the same radiotherapy/ADT backbone plus docetaxel for 3 cycles at 60 mg/m2 once every 3 weeks before radiotherapy and then 20 mg/m2 for 7 cycles once weekly during radiotherapy.

Less radiotherapy–induced cancers and related deaths were observed among patients in the docetaxel arm (1 death) versus patients in the ADT plus radiotherapy arm (8 deaths; age-adjusted HR, 0.13; 95% CI, 0.02-0.97; P = .046). Further, 10-year cumulative incidence estimates were 0.61% (95% CI, 0.06%-3.09%) versus 4.90% (95% CI, 2.13%-9.40%) in the docetaxel and ADT plus radiotherapy arms, respectively.

When comparing patients with a PSA less than 4 ng/mL and patients with a PSA of 4 to 20 ng/mL, the treatment effects of adding docetaxel to ADT plus radiotherapy resulted in a difference in OS (HR, 0.33, 1.40; P = .09; aHR, 0.27, 1.51; P = <.05)).

Treatment discontinuations due to toxicity were reported in 7 patients in the docetaxel arm and 8 patients in the ADT plus radiotherapy arm. Acute adverse effects were reported in 26.90% and 10.34% of patients in the docetaxel and ADT plus radiotherapy arms, respectively, with most effects being grade 2 or 3 in severity in both arms (18.13% and 8.05%, respectively).

“The ability to significantly reduce [radiotherapy]–induced cancer incidence is clinically relevant given that these cancers are typically radiation- and chemotherapy-resistant and, as a result, often fatal as observed in this study,” the investigators explained.


D'Amico AV, Xie W, McMahon E, et al. Radiation and androgen deprivation therapy with or without docetaxel in the management of nonmetastatic unfavorable-risk prostate cancer: a prospective randomized trial. J Clin Oncol. 2021;39(26):2938-2947. doi:10.1200/JCO.21.00596

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