IDEAL 2a Phase II Study of Ultrafocal Brachytherapy for Low- and Intermediate-risk Prostate Cancer

Abstract

Focal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterized index tumors (ITs). We assessed the feasibility of low-dose-rate ultrafocal brachytherapy. The present study was an institutional review board-approved European Clinical Trials Database-registered phase II protocol. Patients referred (October 2013 to August 2016) for active surveillance (prostate-specific antigen <10ng/mL, cT1c-cT2a, Gleason score on referring biopsy specimens ≤6 (3+3), ≤3 positive biopsy cores, ≤50% of cancer) were preselected. Inclusion was confirmed when complementary image-guided biopsy findings informed a single Prostate Imaging Reporting and Data System (PI-RADS) ≥3, Gleason score ≤7a (3+4) lesion. A ultrasound-visible ancillary marker was positioned within the IT using a magnetic resonance imaging (MRI)/3-dimensional transrectal ultrasound (TRUS) elastic fusion-guided system (Koelis). Ultrafocal transperineal delivery of 125I seeds used classic 2-dimensional TRUS (Bard-FlexFocus) and dose optimization (Variseed Treatment Planning System). Following Simon's optimal design, 17 patients were required to assess the feasibility of delivering ≥95% of the prescribed dose (160Gy) to the IT (primary objective). Adverse events (Common Terminology Criteria for Adverse Events) and quality of life (5-item International Index of Erectile Function, International Prostate Symptom Score) were recorded. One-year control biopsy specimens were obtained from the IT and untreated segments. Of the 44 preselected patients, 27 did not meet the inclusion criteria. Of the 17 ultrafocal brachytherapy-treated patients, 16 met the primary objective (per protocol success). The prescription dose was delivered to 14.5%±6.4% of the prostate volume, resulting in negligible urethral and rectal irradiation and toxicity. No recurrence was evidenced on the 1-year follow-up MRI studies or IT biopsy specimens. Seven nonclinically significant cancers and one Gleason score 7a (3+4) cancer (salvage prostatectomy) were observed in the untreated parenchyma. Recent technology has allowed for selective and effective brachytherapy of small MRI targets.