MRI-Guided Transurethral Ultrasound Ablation in Patients with Localized Prostate Cancer: 3-Year Outcomes of a Prospective Phase I Study
MRI-guided transurethral ultrasound ablation (TULSA) is a novel minimally-invasive technology for ablation of benign and malignant prostate tissue. The transurethral device emits directional ultrasound to ablate a volume shaped to patient-specific anatomy using active MRI thermometry feedback control. We present 36 month (mo) follow-up for a multi-center prospective Phase I study of the safety and feasibility of MRI-guided TULSA for near whole-gland ablation in patients (pts) with localized prostate cancer (PCa).
30 pts with biopsy-proven organ-confined PCa (T1c-T2a, PSA ? 10 ng/ml, Gleason Score 3+3, ? 3+4 in Canada only) were treated. MRI-guided TULSA was delivered with mandated 3 mm safety margins expected to preserve 10% untreated viable tissue at periphery. Primary endpoints were safety and feasibility (spatial precision of conformal ablation). Exploratory outcomes included quality of life, PSA, MRI, and biopsy.
Median (IQR) age was 69 (67-71) years and PSA 5.8 (3.8-8.0) ng/ml, with 24 (80%) low-risk and 6 (20%) intermediate-risk PCa. Treatment time was 36 (24-44) min and prostate volume 44 (38-48) cc. Spatial control of ablation was ± 1.3 mm. Adverse events (CTCAE v4) included urinary tract infections (10 pts G2), acute retention (3 pts G1; 5 pts G2), and epididymitis (1 pt G3). No rectal injuries or fistulae. Pre-treatment IPSS of 8 (5-13) and IIEF of 13 (6-28) returned to 6 (4-10) at 3 mo and 13 (5-25) at 12 mo, and 7 (4-11) and 8 (2-23) at 36 mo, respectively. Median PSA decreased 87% at 1 mo, and was stable to 0.8 (0.6-1.1) ng/ml at 12 mo (n=30) and 0.8 (0.4-1.6) ng/ml at 36 mo (n=22). PSA nadir was 0.5 (0.2-0.8) ng/ml. MRI at 12 mo shows 88% (83-95%) prostate volume reduction, matching treatment plan. 12 mo biopsy found disease in 16/29 pts (55%), clinically significant in 9/29 pts (31%). 5 pts underwent salvage prostatectomy with no surgical complications, 1 pt salvage radiotherapy, and 1 pt MRI-guided laser ablation. At 36 mo 1/13 pts with negative 12 mo-biopsy had 3+3 disease; 1/9 remaining pts with positive 12 mo-biopsy upstaged to 3+4, and 4/9 downstaged with 3+3 or negative biopsy.
With 3-year follow-up MRI-guided TULSA appears to provide precise, minimally-invasive near whole-gland ablation for pts with localized PCa, with low morbidity; without precluding salvage therapy. A 110 pt multi-center trial evaluating safety and efficacy of complete whole-gland ablation is underway.
Funding: Profound Medical Inc.