Docetaxel Addition to Radiation and ADT for Nonmetastatic Unfavorable-Risk Prostate Cancer

Although docetaxel is not recommended for managing men with unfavorable-risk prostate cancer (PC) due to negative or inconclusive results from previous randomized trials, potential unexplored advantages may exist. From September 21, 2005, to January 13, 2015, 350 males with T1c-4N0M0 unfavorable-risk prostate cancer were randomly allocated in a 1:1 ratio. The first group received a combination of radiation therapy (RT) and androgen deprivation therapy (ADT), along with docetaxel (60 mg/m² administered once every 3 weeks for three cycles before RT, and 20 mg/m² once weekly during RT). The second group received ADT along with RT. The treatment effect of incorporating docetaxel into androgen deprivation therapy (ADT) and radiation therapy (RT) was assessed in terms of the primary outcome measure of overall survival (OS).

The occurrence of radiation therapy-induced cancers was examined, along with an investigation into whether the treatment’s effect on overall survival varied among different prostate-specific antigen (PSA) subgroups (<4, >20 v 4-20 ng/mL). This was done using the interaction test for heterogeneity while considering age and prognostic factors related to prostate cancer. Following a median follow-up duration of 10.2 years, 89 male individuals experienced mortality (25.43%). Among these cases, 42 deaths were attributed to prostate cancer (47.19%). Although overall survival (OS) did not show a significant increase in the docetaxel treatment group (the restricted mean survival time over 10 years was 9.11 years compared to 8.82 years in the control group; P = .22), there was a significant reduction in the occurrence of radiation therapy (RT)-induced cancers (10-year estimates: 0.61% compared to 4.90%; age-adjusted hazard ratio of 0.13; 95% confidence interval, 0.02 to 0.97; P = .046).

The therapeutic impact of incorporating docetaxel into androgen deprivation therapy (ADT) and radiation therapy (RT) on overall survival (OS) exhibited a notable disparity between males with a prostate-specific antigen (PSA) level below 4 ng/mL and those with a PSA level ranging from 4-20 ng/mL. This discrepancy was observed through adjusted hazard ratios of 0.27 and 1.51, respectively. This difference can be attributed to a lower incidence of prostate cancer-specific mortality in the group receiving docetaxel (0.00% versus 28.57%) among males with a PSA level below 4 ng/mL. The addition of docetaxel to androgen deprivation therapy (ADT) and radiation therapy (RT) did not result in a prolongation of overall survival (OS) in men with unfavorable-risk prostate cancer (PC). However, it did lead to a decrease in the incidence of cancer induced by RT, and there is a possibility that it may prolong OS in a specific subgroup of men with a prostate-specific antigen (PSA) level below 4 ng/mL by reducing mortality related explicitly to PC.

Source: https://pubmed.ncbi.nlm.nih.gov/34197181/

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT00116142

D’Amico AV, Xie W, McMahon E, Loffredo M, Medeiros S, Joseph D, Denham J, Kumar P, Bubley G, Sullivan M, Hellwig R, Carlos Vera J, Freter R, Jeffrey Baker W, Wong JY, Renshaw AA, Kantoff PW. 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 Sep 10;39(26):2938-2947. doi: 10.1200/JCO.21.00596. Epub 2021 Jul 1. PMID: 34197181; PMCID: PMC8425842.