Prostate cancer represents the second most common malignancy in men worldwide. Oligometastatic prostate cancer (OMPC), defined as a transitional state between localized and widespread metastatic disease (≤10 metastatic lesions without visceral metastases), exhibits relatively indolent biological behavior, offering a window for curative-intent multimodal therapy. While standard systemic therapy with androgen deprivation therapy (ADT) plus novel hormonal agents (NHA) remains the backbone for metastatic hormone-sensitive prostate cancer (mHSPC), emerging evidence suggests that maximal cytoreductive therapy-combining systemic treatment with local interventions (Radical prostatectomy(RP) and Metastasis-directed radiotherapy(MDT))-may improve survival outcomes. Rezvilutamide (SHR3680), a novel androgen receptor inhibitor independently developed by a Chinese pharmaceutical company, has demonstrated superior radiographic progression-free survival (rPFS) and overall survival (OS) compared to bicalutamide in high-volume mHSPC (CHART study). However, the value of adding metastasis-directed radiotherapy (MDRT) to rezvilutamide and radical prostatectomy in OMPC remains unproven. This trial hypothesizes that maximal cytoreductive therapy (systemic therapy + surgery + MDRT) will significantly prolong progression-free survival (PFS) compared to systemic therapy alone. This is a multicenter, three-arm, open-label, randomized controlled phase II clinical trial (Protocol No.: MA-PCa-II-023; Lead Investigator: Prof. Bo Dai, Fudan University Shanghai Cancer Center). The study will enroll 300 patients randomized in a 2:2:1 ratio to: Arm A (Experimental): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (if PSA decline ≥50%, castrate testosterone level, and resectable disease) → MDT (SBRT 30-40 Gy/3-5 fractions) to all evaluable metastases at month 6 ( 3 month post-surgery) Arm B (Control): Rezvilutamide (240 mg QD) + ADT alone Arm C (Factorial): Rezvilutamide (240 mg QD) + ADT → radical prostatectomy at month 3 (without MDT) Eligible patients are males ≥18 years with histologically confirmed prostate adenocarcinoma (no neuroendocrine differentiation), newly diagnosed mHSPC with oligometastatic disease (≤10 bone/lymph node metastases on conventional imaging; no visceral metastases), and planned ADT. Key exclusion criteria include prior radical prostatectomy, pelvic radiotherapy, systemic therapy for prostate cancer (except ≤4 weeks of ADT), or contraindications to surgery/radiotherapy. The primary endpoint is PFS, defined as time from randomization to first biochemical progression (PSA rise ≥25% and ≥1 ng/mL above nadir confirmed after ≥3 weeks), radiographic progression (RECIST 1.1/PCWG4), clinical progression (new symptoms from local/metastatic disease), or death. Secondary endpoints include rPFS, OS, PSA response rates (PSA50/PSA90), local therapy completion rate, time to CRPC, quality of life (FACT-P and EPIC-26 questionnaires), and safety profiles. Exploratory endpoints evaluate the role of baseline PSMA PET/CT in staging and the development of artificial intelligence models using multimodal data (clinical, imaging, pathology, molecular) to predict prognosis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
Metastasis-directed radiotherapy (MDRT; SBRT 30-40 Gy/3-5 fractions to all evaluable metastases) at 3 months post-surgery
Rezvilutamide (240 mg daily) plus ADT alone until progression or unacceptable toxicity.
Radical prostatectomy with extended pelvic lymph node dissection (ePLND), including removal of the prostate gland, seminal vesicles, and bilateral pelvic lymph node groups (obturator, internal iliac, external iliac, and common iliac nodes), performed in patients with oligometastatic prostate cancer
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Progression-free survival (PFS)
Time from randomization to the first occurrence of biochemical progression, radiographic progression, clinical progression, or death. Biochemical progression: (1) For patients with PSA decline from baseline: PSA increase ≥25% and ≥1 ng/mL above nadir, confirmed by repeat testing ≥3 weeks later; or (2) For patients without PSA decline: PSA increase ≥25% and ≥1 ng/mL above baseline after ≥12 weeks of treatment. Radiographic progression: Disease progression per RECIST 1.1 (soft tissue) and PCWG4 (bone) criteria. Clinical progression: New symptoms due to local disease progression, lymph node involvement, or systemic metastases (e.g., pathologic fracture, spinal cord compression, worsening pain unresponsive to symptomatic treatment).
Time frame: up to 72 months
Radiographic PFS (rPFS)
Time from randomization to first radiographic disease progression (RECIST 1.1 for soft tissue; PCWG3 for bone) or death.
Time frame: up to 72 months
Overall Survival (OS)
Time from randomization to death from any cause.
Time frame: up to 72 months
PSA Response Rates
Proportion of patients achieving PSA50 (≥50% decline), PSA90 (≥90% decline), or undetectable PSA (\<0.2 ng/mL).
Time frame: up to 72 months
Local Therapy Completion Rate
Proportion of patients in experimental arms completing all planned local therapies (surgery ± radiotherapy).
Time frame: up to 72 months
Time to CRPC
Time from randomization to castration-resistant prostate cancer (disease progression per PSA or imaging criteria despite castrate testosterone levels \<50 ng/dL).
Time frame: up to 72 months
3-Year PSA Progression-Free Survival Rate
Proportion of patients without PSA progression at 3 years.
Time frame: up to 72 months
Time to PSA Progression
Time from randomization to PSA progression (same criteria as biochemical progression in PFS).
Time frame: up to 72 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.