Cytoreductive radical prostatectomy in patients with high-volume metastatic prostate cancer achieving deep biochemical response to contemporary systemic therapy: a multicentre, prospective cohort study

BACKGROUND: Cytoreductive radical prostatectomy (CRP) may improved outcomes in men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its roles in high-volume disease remains controversial. Contemporary systemic therapy has enabled an increasing proportion of patients with high metastatic burden to achieve deep disease remission, creating a potential window to assess additional benefit from primary tumor resection. We aimed to investigate the feasibility and oncological outcomes of CRP in patients with mHSPC, including those with high-volume disease. METHODS: This multicentre, prospective study recruited patients with histologically diagnosed mHSPC from September, 2018 to October, 2023. All eligible patients received lifelong androgen deprivation therapy combined with novel androgen receptor pathway inhibitors and achieved a deep biochemical response (prostate-specific antigen [PSA] < 0.2 ng/ml). Patients either underwent CRP plus standard of care (SOC) or received SOC only. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were overall survival (OS) and PSA progression-free survival (PSA-PFS). Multivariable Cox proportional hazards models, incorporating CRP as a time-dependent covariate, were used to evaluate associations with outcomes. Propensity score matching (PSM) was applied to balance baseline characteristics between groups. RESULTS: Of 126 patients enrolled, 62 underwent CRP + SOC and 64 received SOC. At a median follow-up of 46.7 months, patients in the CRP + SOC group demonstrated prolonged survival compared with those receiving SOC alone. Among 74 patients with high-volume diseases, CRP remained associated with significant longer rPFS (hazard ratio [HR] 0.36, p = 0.035), OS (HR 0.10, p = 0.006), and PSA-PFS (HR 0.32, p = 0.017). Multivariate Cox regression analysis identified CRP as an independent prognostic factor (all p < 0.05). After PSM, 30 well-balanced pairs were identified. In the matched cohort, CRP + SOC was consistently showed improved rPFS (HR 0.31, p = 0.036), OS (HR 0.22, p = 0.031), and PSA-PFS (HR 0.25, p = 0.009) compared with SOC alone. CONCLUSIONS: CRP is feasible and associated with improved oncological outcomes in well-selected patients with mHSPC who achieved deep biochemical response to contemporary systemic therapy, including those with high-volume metastatic disease. However, these findings require validation in larger, prospective, randomized controlled trials.