Preoperative ADT combined with docetaxel for conversion therapy in large-volume and unresectable locally advanced or oligometastatic prostate cancer: a multicenter retrospective study (YHCG-001 study)

Background: The value of radical prostatectomy (RP) in large volume and unresectable locally advanced prostate cancer (LAPC) or oligometastatic prostate cancer (OMPC) is largely unknown. This retrospective study aims to evaluate the conversion efficacy and safety profile of preoperative androgen deprivation therapy combined with docetaxel (A + D) in patients with large-volume (≥60 mL) and initially unresectable LAPC or OMPC. Methods: Patients with LAPC or OMPC from three large tertiary medical centers (between April 2017 and October 2024) were included. Eligibility criteria included prostate volume ≥60 mL, unresectability, and an expected survival of more than 5 years, as confirmed by two senior urologists and one radiologist. All patients received preoperative A + D therapy (≥3 cycles), followed by reassessment for RP feasibility with multimodal therapy discussion. The primary endpoint was surgical conversion rate. Secondary endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), overall survival (OS), PSA response rate, adverse events, pathological response, perioperative complications, urinary continence, and sexual function. Results: Among 31 enrolled patients, the mean age was 67.71 ± 6.69 years, and 29 (93.55%) successfully underwent RP. The mean follow-up duration was 42.83 ± 23.58 months (up to October 2024). Median PSA-PFS was 49 months (95% CI: 24.20–73.79 months), and median OS was not reached. Hematologic toxicity was the most common adverse event during chemotherapy. After A + D therapy, median prostate tumor volume decreased from 67.50 mL to 25.81 mL, and median PSA declined from 168 to 0.49 ng/mL. After RP, 11 patients (37.93%) experienced a downgrade in Gleason score, and 14 patients (48.28%) experienced a downgrade in T-stage. Positive surgical margins were found in 11 patients (37.93%). Perioperative complications included blood transfusion (11.11%), rectal injury (3.70%), lymphorrhea (7.41%), and fever >38.5°C (3.70%). The 1-year urinary continence rate was 89.66%, while 100% of patients experienced sexual dysfunction. Conclusion: Preliminary data suggest that preoperative A + D therapy followed by RP may be integrated into multimodal management for large-volume, initially unresectable LAPC and OMPC, demonstrating promising conversion efficacy and clinical outcomes.