Introduction:

Conventional treatments for localized prostate cancer (PCa) are effective but can leave men with significant functional impairment. In selected patients, ablative therapies are positioned as a safer alternative to radiation therapy or radical prostatectomy (RP), although the establishment of ablative therapies in the standard of care awaits level one evidence. Historically, randomized controlled trials (RCTs) in this setting have struggled or even failed to recruit due to poor patient acceptance of randomization. Here, we report the design of a RCT comparing TULSA (MRI-guided transurethral ultrasound ablation of the prostate) against RP. Based on TULSA safety and efficacy data from the 115-patient TACT pivotal study and accumulating real-world evidence, CAPTAIN was designed to test a superiority hypothesis for safety, and non-inferiority for efficacy. Strategies to mitigate the risk of failure to recruit include a 2:1 TULSA:RP allocation strategy, peer-to-peer education, and expansion into additional sites and sub-sites.

Methods:

The CAPTAIN study (NCT05027477) is a multi-center, open-label, randomized controlled trial that will enroll 201 patients with organ-confined, NCCN intermediate-risk GG 2/3 PCa. Patients will be randomized to receive up to two TULSA procedures with subtotal to whole-gland ablation plans, or RP without restriction on surgical approach. Crossover is not permitted. The primary safety endpoint (superiority) is preservation of IIEF Q2≥2 potency and EPIC Q5 pad-free continence at 1 year. The primary efficacy endpoint (non-inferiority within a margin of 10%) is freedom from additional intervention for PCa, metastatic disease, or PCa-specific death. Secondary endpoints include PSA and survival to 10 years, complications to 5 years, and post-TULSA MRI and biopsy. From Jan 2022-July 2024, 18 sites were activated including 4 sub-sites. During this period, 145 patients (>70%) were randomized. 16 patients (11%) withdrew consent after randomization and before treatment: 4 developed comorbidities and became medically unfit for treatment, and 12 refused allocation. Experience at top-recruiting sites underscores the importance of departmental engagement, streamlined processes for identifying candidates, and having high-volume prostatectomy groups offer the study to patients who favor RP.

Results:

Conclusion:

Funding: The study is supported by Profound Medical.