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Background <p>The management of metastatic castration-resistant prostate cancer (mCRPC) following progression on androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI) in the castration-sensitive (CS) setting remains unclear. Limited data exist comparing the efficacy of ARPI versus docetaxel as first-line treatment in this context.</p> Methods <p>We conducted a retrospective multicentre study across three tertiary cancer centres in Saudi Arabia, including 60 patients with pathologically confirmed mCRPC who progressed after doublet therapy (ADT + ARPI) in the CS setting between January 2018 and September 2022. Patients received either ARPI (abiraterone acetate or enzalutamide) or docetaxel as first-line therapy for mCRPC. Primary endpoints were prostate-specific antigen (PSA) response rate and biochemical progression-free survival (PFS). Secondary endpoints included overall survival (OS) and treatment patterns. PSA response was defined as ≥ 30% decline at 12 weeks from baseline. Survival analyses were performed using Kaplan-Meier and log-rank tests.</p> Results <p>Among 60 eligible patients (median age 65 years), 28 received ARPI and 32 received docetaxel. PSA response rates were 39.3% for ARPI and 37.5% for docetaxel. Median PFS was 2.9 months (95% CI 0.37–5.5) for ARPI and 4.5 months (95% CI 2.6–6.3) for docetaxel (<i>p</i> = 0.137). Median OS was 13 months (95% CI 4.0–23.9) for ARPI and 16 months (95% CI 6.1–25.9) for docetaxel (<i>p</i> = 0.236). In patients with visceral metastases, docetaxel conferred significantly longer OS compared to ARPI (14.4 vs. 5.9 months, <i>p</i> = 0.025). Multivariate analysis identified nadir PSA in the CS setting as a predictor of PFS and first-line therapy in the CR setting, visceral metastasis and duration of therapy in CS setting as predictors of OS.</p> Conclusions <p>In patients progressing to mCRPC after doublet therapy in the CS setting, docetaxel demonstrated a trend toward longer PFS and OS compared to ARPI, with a significant survival advantage in those with visceral metastases. These findings highlight the need for prospective randomized trials and biomarker-driven treatment strategies to optimize therapy sequencing in this evolving treatment landscape.</p>

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Docetaxel versus androgen receptor pathway inhibitors as first-line therapy for metastatic castration-resistant prostate cancer after doublet therapy: a multicenter retrospective study from Saudi Arabia

  • 期刊论文

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  • 发表日期：

    2025年12月22日

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  • Shouki Bazarbashi,
  • Ahmed S. Abdelmotal,
  • Tarek Arabi,
  • Waleed Fallatah,
  • Noura Alzannan,
  • Tusneem Elhassan,
  • Mohamed Aseafan,
  • Mohammed Mahroos,
  • Maram Aljishi,
  • Albatool Busbaih,
  • Rajaa Aldandan,
  • Muhammad Shahzad Rauf,
  • Fahad A Almugbel,
  • Faisal Azam,
  • Mubarak Almansour

摘要

Background

The management of metastatic castration-resistant prostate cancer (mCRPC) following progression on androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI) in the castration-sensitive (CS) setting remains unclear. Limited data exist comparing the efficacy of ARPI versus docetaxel as first-line treatment in this context.

Methods

We conducted a retrospective multicentre study across three tertiary cancer centres in Saudi Arabia, including 60 patients with pathologically confirmed mCRPC who progressed after doublet therapy (ADT + ARPI) in the CS setting between January 2018 and September 2022. Patients received either ARPI (abiraterone acetate or enzalutamide) or docetaxel as first-line therapy for mCRPC. Primary endpoints were prostate-specific antigen (PSA) response rate and biochemical progression-free survival (PFS). Secondary endpoints included overall survival (OS) and treatment patterns. PSA response was defined as ≥ 30% decline at 12 weeks from baseline. Survival analyses were performed using Kaplan-Meier and log-rank tests.

Results

Among 60 eligible patients (median age 65 years), 28 received ARPI and 32 received docetaxel. PSA response rates were 39.3% for ARPI and 37.5% for docetaxel. Median PFS was 2.9 months (95% CI 0.37–5.5) for ARPI and 4.5 months (95% CI 2.6–6.3) for docetaxel (p = 0.137). Median OS was 13 months (95% CI 4.0–23.9) for ARPI and 16 months (95% CI 6.1–25.9) for docetaxel (p = 0.236). In patients with visceral metastases, docetaxel conferred significantly longer OS compared to ARPI (14.4 vs. 5.9 months, p = 0.025). Multivariate analysis identified nadir PSA in the CS setting as a predictor of PFS and first-line therapy in the CR setting, visceral metastasis and duration of therapy in CS setting as predictors of OS.

Conclusions

In patients progressing to mCRPC after doublet therapy in the CS setting, docetaxel demonstrated a trend toward longer PFS and OS compared to ARPI, with a significant survival advantage in those with visceral metastases. These findings highlight the need for prospective randomized trials and biomarker-driven treatment strategies to optimize therapy sequencing in this evolving treatment landscape.