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The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trials showed that the addition of docetaxel (D) to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most commonly used first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), we aimed to assess whether they maintained their efficacy after ADT+D versus ADT alone.A cohort of patients with mCRPC treated between 2014 and 2017 with first-line AA or E for mCRPC was identified from 3 hospitals’ institutional review board-approved databases. Patients were classified by use of D for mHSPC. This time frame was chosen as ADT+D became a valid therapeutic option for mHSPC in 2014, and it inherently entailed a short follow-up time on AA/E. The endpoints included overall survival from ADT start, overall survival from AA/E start, and time to AA/E start from ADT start. Differences between groups were assessed using the log-rank test.Of the 102 patients with mCRPC identified, 50 (49%) had previously received ADT alone, while 52 (51%) had ADT+D. No statistically significant difference in any of the evaluated outcomes was observed between the 2 cohorts. Yet, deaths in the ADT+D group were 12 versus 21 in the ADT alone, after a median follow-up of 24.4 and 29.8 months, respectively.In a cohort of ADT/ADT+D-treated patients with mCRPC with short times to first-line AA/E and follow-up, the efficacy of AA/E is similar regardless of previous use of D.Although an androgen deprivation therapy plus docetaxel regimen was shown to extend the survival of some patients with metastatic hormone-sensitive prostate cancer compared with androgen deprivation therapy alone, currently, there is no report in the literature investigating the impact of upfront docetaxel on subsequent first-line abiraterone acetate or enzalutamide for metastatic castration-resistant prostate cancer. This study showed that their activity is maintained regardless of previous use of docetaxel for metastatic hormone-sensitive prostate cancer. These findings can aid treatment decision-making.