Focal MR-Guided High-Dose-Rate Brachytherapy for Localized Prostate Cancer: A Prospective Clinical Trial

Abstract

<h3>Purpose/Objective(s)</h3> Focal therapy has gained traction in the management of localized prostate cancer (PCa) based on the promise of equivalent oncologic outcomes with minimal toxicity compared to whole gland therapy. However, 20-45% of patients have persistent/recurrent disease within the first 2-5 years after most commonly-used ablative methods (e.g., HIFU, cryotherapy). Based on brachytherapy's (BT) well-established and long track-record of efficacy for PCa, we sought to test the focal therapy hypothesis in a prospective clinical trial of MR-guided HDR for men with localized PCa. <h3>Materials/Methods</h3> This prospective trial was approved in 2016 (UHN IRB# 16-5490; NCT02918253) for patients with clinically low- and favorable intermediate-risk prostate cancer, and a conspicuous lesion on mpMRI consistent with the area of pathological involvement. The CTV was derived from the mpMRI-defined GTV plus a 7 mm isotropic expansion, with 2 mm sup/inf added for the PTV. Implant and planning were performed with an MR-only workflow, and delivery with HDR BT. Treatment consisted of two separate implants within 14 days, to a prescription dose of 33-36 Gy in 2 sessions (BED ≥ 200 Gy). Biochemical recurrence (BCR), defined as > 2ng/mL above nadir was calculated using the Kaplan Meier method. Local failure, distant metastasis (DM) and toxicity events are reported as absolute rates. <h3>Results</h3> Nineteen patients have been treated, with a median age of 73 years (range 48-84), and median follow-up of 24 months (8-63). Median PSA was 6.1 ng/mL and 17/19 patients had Grade Group 2 disease. On average, the GTV and PTV corresponded to 3.56% (1.58-12.07) and 23.16% (13.71-40.75) of the median prostatic volume (40.49 cc [25.57-97.6]). Median number of catheters was 7 (4-11). Median GTV D₉₉ and PTV D₉₅ per fraction were 23.82 Gy (18.50-31.89) and 18.71 Gy (16.01-20.64), respectively. Nine patients have undergone the 2-yr local control ascertainment; 7 with mpMRI plus biopsies, and 2 with mpMRI only. At 2-years, local control and BCR-free survival were 100%; a single BCR event has been recorded 34 months after treatment. No DM or death events have occurred. The rate of treatment-related acute and late toxicities that were graded ≥ 2 was 0%. <h3>Conclusion</h3> Focal MRI-guided HDR brachytherapy as monotherapy appears to have a high therapeutic ratio and is a promising technique for localized PCa. Further follow-up will determine the durability of outcomes with this approach and the need for collaborative randomized studies.