OCOG-RATIONAL: A phase II randomized trial of optimal recurrence-directed therapy (RDT) without or with androgen-deprivation therapy (ADT) in radio-recurrent oligo-metastatic castrate sensitive prostate cancer (romCSPC).

TPS305 Background: This is a Canadian, multi-center study that investigates whether addition of ADT to RDT improves oncological outcomes in early romCSPC. The primary outcome is a 36-month composite Progression-free survival (cPFS). Secondary outcomes include metastasis-free survival, time to salvage therapy, time to castrate-resistant PC, OS, Quality of Life and toxicity. Methods: Population: Patients with biochemical recurrence after definitive or adjuvant/salvage radiotherapy for localized prostate cancer (PC) with oligo-metastatic disease (≤5 sites) without or with local recurrence. All patients will be staged with conventional imaging (CT/BS), mpMRI, PSMA-PET and biopsy of the prostate if in situ. Randomization: Patients are randomized 1:1 to RDT versus RDT+ADT for 12 months and stratified for, i) presence of local recurrence (Y/N), ii) volume of metastatic disease [0 (local recurrence alone) versus 1-3 versus 4-5 metastases]. iii) treatment centre, and iv) metastasis detected on conventional imaging (Y/N). Interventions: RDT options include Stereotactic Body Radiotherapy (SBRT), hypo-fractionated radiotherapy (HFRT), brachytherapy and surgical resection. Concurrent and adjuvant ADT involves four 3-month leuprolide acetate injections. Statistics: A clinically meaningful improvement for the use of ADT is defined as an improvement in the 30-month cPFS of ≥20% (from 50% to 70%). With an expected accrual period of 3 years, an additional 1 year of follow-up, a 1-sided log-rank test with α=0.05 would have over 80% power to distinguish between the two group with 73 patients in each arm. This number is inflated by 10% for stratification factors and patients lost-to-follow-up, for a total of 162 patients. Coordination: The study is coordinated by the Ontario Clinical Oncology Group (OCOG) and is expected to open in 10-12 institutions across Canada. This trial will provide evidence on the impact of ADT in romCSPC managed with optimal recurrence directed therapy. Findings will support phase III trial design to help define the optimal management of romCSPC in the future. Clinical trial information: NCT06654336 .