193 Background: For newly diagnosed high-volume metastatic hormone-sensitive prostate cancer (mHSPC), front-line therapy typically involves androgen-deprivation therapy (ADT) combined with either docetaxel or novel androgen-receptor inhibitors. The role of local treatment (such as cytoreductive prostatectomy or radiation therapy) in men with a high-volume of metastases is not well established. We investigated a strategy of intensive systemic triplet therapy (ADT and darolutamide and docetaxel) followed by robot‐assisted cytoreductive prostatectomy. Methods: In this prospective, single-center study, 30 patients with high-volume mHSPC received six months of intensive therapy (NCT06350825). All patients underwent preoperative evaluation after systemic therapy, during which they achieved ≥90% reduction in PSA (PSA90) and showed no radiographic progression on PSMA PET/CT before proceeding to robot-assisted cytoreductive prostatectomy. The aim was to assess the impact of this multimodal therapy on PSA response, pathological outcomes, and the feasibility of combining systemic therapy with surgery. After surgery, patients continued systemic therapy to evaluate long-term outcomes. Results: With a median follow-up of 20.5 months, survival data remained immature. All patients achieved PSA90, and 73.3% had PSA levels ≤0.2 ng/mL following the intensive systemic therapy. Postoperative pathological analysis showed significant tumor regression: 73.3% of patients were pathologically downstaged. Notably, 7 of 30 patients (23.3%) had either pathologic complete response or minimal residual disease. The triplet regimen was well tolerated, with no grade III or higher adverse events. Only 5 patients (16.7%) experienced grade I–II adverse events, including 2 cases of anastomotic leak, 1 case of pneumonia, and 2 cases of urinary tract infection. These adverse events were all resolved with standard care. At 12 months post‐surgery, 93% of patients reported mild urinary incontinence, as expected following cytoreductive prostatectomy, with no life-threatening surgical complications. Conclusions: This is the first prospective study to explore a darolutamide-based triplet induction regimen followed by cytoreductive prostatectomy in high-volume mHSPC. The results demonstrate that this multimodal approach is both feasible and safe, leading to deep PSA remissions and significant pathological tumor regression. These findings suggest that aggressive induction therapy, followed by prostatectomy, can yield significant clinical responses. However, further randomized trials with longer follow-up are needed to fully assess its impact on long-term survival. Clinical trial information: NCT06350825 .
Wang et al. (Sun,) studied this question.