An open-label, parallel-cohort, multicenter clinical study of rezvilutamide in combination with androgen deprivation therapy (ADT) with or without docetaxel in the neoadjuvant treatment of oligometastatic prostate cancer.

TPS5148 Background: Oligometastatic hormone-sensitive prostate cancer (omHSPC), defined by ≤5 metastases, represents a distinct disease state with a more favorable prognosis, offering a critical window for treatment intensification aimed at improving long-term outcomes. Cytoreductive radical prostatectomy (cRP) has emerged as a feasible local treatment option for select patients, with phase II data suggesting a survival benefit over systemic therapy alone. The foundation of systemic therapy for metastatic HSPC (mHSPC) is an androgen receptor pathway inhibitor (ARPI) combined with androgen deprivation therapy (ADT). Rezvilutamide, a second-generation ARPI, demonstrated superior efficacy over bicalutamide when combined with ADT in patients with mHSPC. Furthermore, the addition of docetaxel to an ARPI and ADT (triplet therapy) significantly improved survival in mHSPC, including in patients with low metastatic burden. We hypothesize that intensifying neoadjuvant systemic therapy with triplet therapy prior to cRP may maximize tumor cytoreduction and pathologic response in omHSPC. Methods: This is a prospective, open-label, parallel-cohort, multicenter phase II study. Patients with newly diagnosed, biopsy-proven omHSPC (≤5 bone or lymph node metastases on conventional imaging, no visceral metastases) who are candidates for and desire cRP are eligible. All patients undergo baseline prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) prior to ADT initiation. Patients select their neoadjuvant regimen: Cohort A receives ADT plus oral rezvilutamide (240 mg daily) for 24 weeks; Cohort B receives ADT, rezvilutamide (same dose), plus docetaxel (75 mg/m² IV q3w for 6 cycles) for 24 weeks. Upon completion of the 24-week neoadjuvant therapy, metastases are reconfirmed by conventional imaging, and a second PSMA-PET/CT assessment is performed. All patients subsequently undergo cRP with extended pelvic lymph node dissection within 6 weeks. After surgery, patients may opt to continue with ADT or rezvilutamide at their discretion until disease progression. Based on assumed pCR rates of <10% (Cohort A) and 25% (Cohort B) (α=0.05, power=80%), 40 evaluable patients are required per cohort. Accounting for 20% dropout, 100 total patients (50 per cohort) will be enrolled. Key inclusion criteria: ECOG PS 0-1, adequate organ function. Key exclusion criteria: prior systemic therapy for PCa (except ≤4 weeks of ADT), prior second-generation ARPI use, and prostate pathology results indicating neuroendocrine carcinoma. As of January 15, 2026, enrollment is ongoing with 6 patients accrued to date. No data analysis has been performed. Clinical trial information: ChiCTR2400093262.