This is a prospective, randomized, open-label, phase II multicenter clinical trial evaluating the efficacy and safety of radical prostatectomy in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who achieve good response after systemic therapy with androgen deprivation therapy (ADT) plus second-generation antiandrogens such as rezvilutamide. All eligible patients will receive 6 months of induction systemic therapy (ADT plus second-generation androgen receptor signaling inhibitors, with or without docetaxel or other systemic agents). Patients who achieve PSMA PET/CT "conversion success" (no metabolically active lesions; all metastases with SUVmax below liver background or blood pool) will be randomized 1:1 to continue systemic therapy alone (control arm) or receive local prostate treatment (radical prostatectomy or radiotherapy) plus systemic therapy (experimental arm). The primary endpoint is radiographic progression-free survival (rPFS). Key secondary endpoints include overall survival (OS), biochemical progression-free survival (bPFS), PSA response rate, quality of life, conversion success rate, and safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
112
Androgen deprivation therapy using LHRH agonists or antagonists (e.g., goserelin, leuprolide, triptorelin, degarelix) according to local prescribing information and CSCO guideline recommendations. The specific drug, dose, and schedule are determined by the investigator and may be adjusted based on tolerability and adverse events.
Intravenous docetaxel may be combined with ADT plus second-generation ARSis in selected patients according to contemporary guideline recommendations and investigator judgment. Dose and schedule follow approved labels and may be modified based on toxicity and tolerability.
Other systemic agents, including PARP inhibitors such as olaparib, may be used in combination with ADT and second-generation ARSis according to approved indications, molecular testing results, guideline recommendations, and investigator judgment.
Radical prostatectomy with bilateral seminal vesicle removal and, when appropriate, pelvic lymph node dissection, performed by experienced urologic surgeons via open, laparoscopic, or robot-assisted approach, in patients randomized to Arm B who have achieved conversion success on PSMA PET/CT
Definitive external-beam radiotherapy to the prostate delivered according to institutional standards and guideline recommendations, as an alternative local prostate treatment for patients randomized to Arm B who have achieved conversion success on PSMA PET/CT and are not undergoing radical prostatectomy
Fudan University Shanghai Cancer Center
Shanghai, China
Radiographic Progression-free Survival (rPFS)
rPFS will be assessed according to RECIST v1.1 and PCWG3 criteria using PSMA PET/CT, contrast-enhanced CT, MRI, or bone scan. Radiographic progression is defined as the appearance of new lesions or growth of existing measurable disease as per RECIST v1.1, or new bone lesions according to the PCWG3 "2+2" rule
Time frame: From randomization to radiographic progression or death from any cause, whichever occurs first, up to approximately 24 months.
Overall Survival (OS)
Time from treatment initiation to death from any cause. Participants alive at last follow-up will be censored.
Time frame: From start of systemic therapy to death from any cause, up to the end of follow-up (approximately 24-30 months).
Biochemical Progression-free Survival (bPFS)
Biochemical progression is defined according to ASTRO/AUA joint guideline: a PSA increase of ≥2 ng/mL above the nadir, confirmed by a second consecutive measurement.
Time frame: From start of systemic therapy to biochemical progression or death, up to ~24 months.
PSA Response Rate at 3 and 6 Months
Proportion of patients with PSA decline ≥50% from baseline at 3 months and 6 months after treatment initiation
Time frame: 3 months and 6 months after treatment
Conversion Success Rate
Proportion of patients who achieve "conversion success" after 6 months of systemic therapy, defined as PSMA PET/CT showing no metabolically active lesions (all metastases with SUVmax below liver background or blood pool) and fulfilling randomization criteria.
Time frame: At 6 months (and 12 months for supplementary randomization, if applicable)
Safety Endpoints
Incidence, type, and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI-CTCAE version 5.0, including treatment-emergent AEs, AEs leading to discontinuation, and treatment-related deaths.
Time frame: From first dose to 30 days after last dose or last study visit
Change from Baseline in EORTC QLQ-C30 Score
Changes from baseline in health-related quality of life measured by EORTC QLQ-C30 (e.g., Global Health Status/QoL and functional scales).
Time frame: From baseline to 3, 6, 12, and 24 months after randomization.
Change from Baseline in SF-36 Score
Changes from baseline in health-related quality of life measured by SF-36 (e.g., PCS and MCS).
Time frame: From baseline to 3, 6, 12, and 24 months after randomization.
Change from Baseline in FACT-G Total Score
Changes from baseline in health-related quality of life measured by FACT-G total score.
Time frame: From baseline to 3, 6, 12, and 24 months after randomization.
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