Impact of Prior Local Treatment on the Outcomes of Metastatic Hormone-Sensitive Prostate Cancer: Secondary Analysis of a Randomized Controlled Trial

Abstract

Background: Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study.

Patients and methods: We performed a retrospective analysis of the prospectively collected data among patients with metastatic HSPC in the CHAARTED study, a phase 3 multicenter study conducted between 2006 and 2014. The CHAARTED study compared androgen deprivation therapy plus docetaxel versus androgen deprivation therapy alone among patients with metastatic HSPC. The main outcomes of the current analysis are overall survival, progression-free survival, prostate cancer-specific survival, and time to castration-resistant disease as assessed by Kaplan-Meier analysis, log-rank testing, and Cox regression models.

Results: Kaplan-Meier overall survival estimates were produced according to whether patients underwent prior local treatment and results were stratified by treatment arm. For both treatment arms, patients with prior local treatment had better overall survival (P < .01). Similarly, Kaplan-Meier progression-free survival estimates were produced according to whether patients underwent prior local treatment, and results were stratified by the treatment arm. For both treatment arms, patients with prior local treatment had better progression-free survival (P < .01). In an adjusted Cox multivariate model (adjusted for assigned study treatment arm, age, baseline prostate-specific antigen, and baseline Gleason score, volume of the disease (low risk or high risk) and baseline performance status), patients with prior local treatment had better overall survival (P = .045), progression-free survival (P = .035), and cancer-specific survival (P = .010) compared to those without prior local treatment. Moreover, they had a longer time to development of castration-resistant disease (P = .025).

Conclusion: Patients with metastatic HSPC and prior local treatment had better overall, progression-free, and cancer-specific survivals compared to those without prior local treatment. The impact of these findings on the treatment paradigms for metastatic HSPC should be thoroughly evaluated.

Keywords: Chemotherapy; Hormonal therapy; Metastatic disease; Prostatectomy; Radiotherapy.