Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

BACKGROUND: Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. OBJECTIVE: To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. INTERVENTION: MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. RESULTS AND LIMITATIONS: Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). CONCLUSIONS: MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. PATIENT SUMMARY: We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. TRIAL REGISTRATION: NCT01686958, DRKS00005311