TULSA is a minimally-invasive technology for ablation of benign and malignant prostate tissue via a transurethral device that emits directional ultrasound to ablate a volume shaped to patient-specific anatomy using active MRI thermometry feedback control. There is no energy through the rectum and no risk of cold spots between discrete sonications. Dr. Klotz has been involved been involved with development of this novel therapy since initiation. The technical/preclinical phase (2000-2012) involved in vivo evaluation of MRI-compatible robotics, directional ultrasound applicators, MRI thermometry, and a feedback control algorithm tested on ~30 canines. In 2010, 8 males were included in a treat-and-resect study, without therapeutic intent, demonstrating that the TULSA procedure was safe and feasible. The ablation boundary in the human prostate was at a temperature of 55 degrees C. Between 2012-2013, five additional patients were included in a treat-and-resect study with whole mount histology, targeting to mpMRI visible lesions identified during TULSA treatment. This demonstrated ablation precision to +/- 1.7 mm on histology and all index tumors within complete tissue ablation zone. From 2013-2014, the trial was rolled out as a safety and precision study among 30 patients with three-year follow-up, demonstrating a favorable profile with a minor impact on quality of life. The PSA and prostate volume reduction matched planned target volume and measured thermal ablation volume (90% of the gland). The objective of today’s presentation was to report preliminary results from the TULSA-PRO Ablation Clinical Trial (TACT) pivotal study of the safety and efficacy of whole-gland ablation for patients with localized prostate cancer.
The TACT trial intended to enroll 110 men with biopsy-proven organ-confined prostate cancer, aged 45-80, with ≤ cT2b, PSA ≤ 15 ng/ml, Gleason Score ≤ 3+4, across 13 centers in USA, Canada, and Europe. MRI-guided TULSA was delivered with intent of whole-gland ablation to the target boundary traced at the prostate capsule. The primary efficacy endpoint was the proportion of patients achieving a PSA reduction ≥ 75%, with secondary endpoints of 12-month biopsy and prostate volume reduction. The primary safety endpoint was the frequency and severity of adverse events in the first 12 months. Secondary quality of life endpoints included urinary incontinence (pads), erectile dysfunction (IIEF-5), IIEF-15, IPSS and EPIC-50.
The study enrolled 115 patients from September 2016 to February 2018. Pre-treatment median (IQR) age was 64 (59-69) years, PSA 6.3 (5.0-8.3) ng/ml, with 39% Gleason 6 and 61% Gleason 7 prostate cancer. There were 34% patients with low-risk disease and 66% with intermediate-risk disease. The median prostate volume was 34 cc (range 15-88cc). There was no rectal injury or fistula, no urinary incontinence > Grade 1, and no Grade ≥ 4 adverse events. Serious attributable AEs included two patients with urinary retention (treated with catheterization/antibiotics), two with culture proven UTI, and one with epididymitis (treated with medications/antibiotics), one with urine extravasation into abdomen (treated with catheterization/drainage), one with ileus (secondary to medication), and one with a DVT (treated with heparin). Among these patients, the median PSA reduction was 95% with a median PSA nadir of 0.36 ng/ml (IQR 0.16-0.60), with 95% of patients meeting the endpoint of ≥ 75% reduction. Currently, the number of patients with 12-month quality of life data is not yet large enough to assess.
Dr. Klotz concluded that the preliminary results of the TACT Pivotal study of MRI-guided TULSA for whole-gland ablation in patients with localized prostate cancer showed that 95% of patients met the primary efficacy criteria of ≥ 75% PSA reduction, and the median PSA reduction was 95% from baseline. There was a high degree of safety and low rate of adverse events. The next steps include assessing further studies recently initiated with regards to targeted therapy, salvage radiation-recurrent therapy and BPH.
Presented by: Laurence Klotz, Sunnybrook Medical Centre, Toronto, Canada
Co-Authors: David Penson, Nashville, TN, Joseph Chin, London, Canada, Christian Pavlovich, Baltimore, MD, James Relle, Royal Oak, MI, Michael Koch, Indianapolis, IN, Gencay Hatiboglu, Heidelberg, Germany, Aytekin Oto, Chicago, IL, Jurgen Futterer, Nijmegen, Netherlands, Steven S. Raman, Santa Monica, CA, Yair Lotan, Dallas, TX, Thorsten Persigehl, Axel Heidenreich, Cologne, Germany, Jose Francisco Suarez, Barcelona, Spain, Robert Staruch, Mathieu Burtnyk, Mississauga, Canada, Alan Pantuck, Santa Monica, CA, JP Sedelaar, Nijmegen, Netherlands, Sandeep S. Arora, Nashville, TN, Gregory Zagaja, Chicago, IL, Temel Tirkes, Indianapolis, IN, Katarzyna Macura, Baltimore, MD, David Bonekamp, Heidelberg, Germany, Masoom Haider, Toronto, Canada, Scott Eggener, Chicago, IL
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre @zklaassen_md at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA