Successful Phase 2 Trial Of Ultrafocal Brachytherapy For Low/Intermediate Risk Prostate Cancer

Focal therapy for localized PCa remains investigational. Because biology suggests the most significant focus drives the natural history, we assessed the feasibility of ultrafocal brachytherapy (BT) targeting the index tumor with a tumoricidal dose of 160 Gy. In a 2-step Simon’s design (&=0.1, ß=0.1), 17 patients were needed to assess that 100% of clinical target volume (CTV) - gross tumor volume on mpMRI plus 2mm margin - received ≥95% of the prescribed dose (primary objective: D100≥152Gy). Pre-inclusion: Patients in accordance to EAU guidelines for both Surveillance [PSA <10ng/mL, cT1c-cT2a, Gleason sum on referring biopsies ≤6 (3+3), ≤3 positive biopsies, ≤50% of cancer] and BT [IPSS <10, no TURP, prostate <60mL, >10yr life expectancy]. Inclusion: Only if institutional mpMRI informed a PIRADS≥3 focal lesion with no extra-prostatic extension and confirmed as Gleason sum ≤7a (3+4) cancer on MRI/3D-TRUS elastic fusion registration (EFR) biopsies (KOELIS, France). Procedure: MRI/3D-TRUS EFR was used to insert trans-rectally a US-visible marker within the biopsy-proven index lesion. The Bard Flex Focus biplanar TRUS system was then positioned as for regular whole-prostate BT. CTV was delineated on transverse sections of the gland using predefined distances to the ancillary marker and anatomical landmarks. Dose distribution was optimized by inverse planning before ultrafocal implantation of I125seeds within CTV. 1ary objective: Doses delivered within the first 30d to CTV were assessed by rigid registration between pre-BT mpMRI (index tumor) and d30 CT-Scan (actual position of implanted I125seeds). 2ary objectives: GI, GU CTCAE toxicity & QoL (IPSS, IIEF5, QLQc30) were prospectively accrued. One year post-BT, biopsies were obtained at the site of treatment and in the untreated segments. 27/44 (61.3%) patients failed confirmatory biopsies (multifocal n=10; aggressive 11; no cancer 6). Of 17 included (10/2013-8/2016), only 3 did not meet the primary objective (D100: 76, 105, 132 Gy) and the trial was deemed successful. Mean CTV was 0.74±0.31mL that is 1.9±1.1% of the gland. Prescribed dose was delivered to <15% of the gland, in line with the ultrafocal nature of the treatment. To date 13 patients, including the previous 3, received 1yr biopsies. No in-field recurrences (CTV) were observed. Five non-clinically significant cancers were found in the contralateral lobe. One bilateral cancer - Gleason sum 7a (3+4) - was detected and planned for salvage surgery. No grade>2 toxicity was observed. QoL was preserved for a large majority. As shown by optimal dosimetry in 14/17 (82.4%), minimal toxicity, and no in-field recurrences (0/13), ultrafocal BT is feasible, efficient and safe. MRI/3D-TRUS EFR biopsies allowed for rigorous selection of suitable patients. Minimal Irradiated volumes within the prostate authorize all therapeutic options if a salvage treatment of the whole gland is ever needed.