Results of a prospective, single-center phase-II study on modern androgen deprivation therapy followed by cytoreductive radical prostatectomy in men with de novo metastatic hormone-sensitive prostate cancer (mHSPC).

197 Background: Cytoreductive prostatectomy (CRP) may provide oncologic benefit for specific patients. The goal of this study is to evaluate overall survival (OS) and progression-free survival (RFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who underwent CRP after induction therapy with modern combined androgen deprivation therapy. Methods: Between 2018 and 2025 85 consecutive patients with mHSPC were entered into a prospective data registry. All men were diagnosed by multiparametric MRI and MRI-fusion biopsies of the prostate. Metastatic disease was diagnosed with molecular imaging by 68Ga or 18F - PSMA-PET/CT in all patients. Men were started on combined androgen deprivation with the use of LHRH-analogues/antagonists and androgen receptor pathway inhibitors such as abiraterone acetate/prednisone, apalutamide or enzalutamide for 6 months. At 6 months, therapeutic response was evaluated by PSA nadir, mpMRI and PSMA-PET/CT. All patients were treated with CRP and pelvic lymphadenectomy; combined ADT was continued for 2 years. Androgen receptor mutations in the ligand binding domain as well as HSB3D1 mutations were analyzed and correlated with outcome. As in Stampede Arm H OS, CSS and MFS at 3 years were calculated. Results: All patients underwent cRP and pelvic lymph node dissection. Mean age was 63 (45-76) years. Median follow-up was 54.1 (12-90) months. Median initial PSA and median PSA at time of surgery was 110 (25-465) ng/ml and 1.25 (<0.01-5.6) ng/ml, resp. M1a, M1b and M1c were present in 28 (20.9%), 98 (73.1%) and 8 (6.0%) men. Pathohistology revealed pT0 in 4 (4.7%) pts and pT2a-c, pT3a/b in 13 (15.3%) and 68 (80%), resp. pN+ and R1 was observed in 37 (43.5%) patients and 29 (34.1%) pts, resp. No local recurrences were observed. Clavien-Dindo grade III and IV complications occurred in 13 (15.3%) and 2 patients. No, mild (1-2 pads/day) or severe incontinence was observed in 67.7%, 18.2%, and 14.1%, resp. 3-year OS, MFS and CSS was 94.6%, 93.7% and 96.8%, resp. Overall survival was 88.5%, median OS was 84 months, median clinical progression free survival was 72 months. OS was significantly inferior in M1 high volume (61.9% vs 92.8%, p=0.002). A high frequency of L702H (18, 2.2%), W742C (30, 35.3%), 0xH875Y, 0x878A, 40xF877L (40, 47%) und HSD3B1 (23, 27%) whereas no mutations for H875Y and T878A were identified. Conclusions: Based on our data, cRP results in an oncological outcome which is at least comparable to RT. One major benefit of cRP is the low rate of local symptomatic failures. Pathohistology demonstrates persistent locoregional viable disease in 2/3 of patients which underlines the need for an effective local therapy. The role of AR and HSD3B1 mutations for PFS and OS will be presented.