Top Line: The NCCN guidelines list docetaxel as an optional addition to radiation and androgen deprivation therapy (ADT) for men with very high risk prostate cancer.
The Study: This randomized trial, designed over 15 years ago, investigated the addition of docetaxel in men with unfavorable intermediate to high risk prostate cancer. 350 men receiving definitive radiation with 6 months ADT were randomized to +/- neoadjuvant and concurrent docetaxel. Docetaxel was given in 10 total cycles: 60 mg/m2 every 3 weeks x 3 cycles prior to radiation and then 20 mg/m2 weekly x 7 cycles during radiation. LHRH agonist and antiandrogen were given for 2 months prior to radiation, 2 months during, and then 2 months after. The prostate and seminal vesicles were treated to 1.8 Gy x 39 = 73.7 Gy normalized to 95% of the target receiving 95% of prescription (70.2 Gy). Unfortunately, there was no improvement in overall survival at 10 years with the addition of docetaxel: 72% were alive after docetaxel versus 74% without docetaxel, and restricted mean survival times (RMST) were 9.1 years versus 8.8 years, respectively. With the hypothesis that docetaxel may improve outcomes specifically in men with low PSA-producing (i.e., ADT-resistant) cancer, an exploratory comparison demonstrated prostate cancer-specific mortality was indeed improved with docetaxel among those with initial PSA < 4 (0% vs 29% at 10 years). To spice things up even more, the authors also found that the rate of “radiation-induced” second cancers was significantly lower with docetaxel (0.6% vs 4.9% at 10 years), hypothesizing that docetaxel sterilizes radiation-damaged cells that may have developed into a secondary cancer. Hm.
TBL: In this mature trial, the addition of docetaxel to radiation and ADT did not improve survival across all men, though a subset of men with ADT-resistant disease may prove to benefit. | D’Amico, J Clin Oncol 2021