Dr. Scott Eggener, on behalf of the TACT collaborators, presents the 1-year outcomes from the TACT study - MRI-Guided Transurethral Ultrasound Ablation (TULSA) in Patients with Localized Prostate Cancer. The preliminary results were presented at last year’s AUA.
As a recap, 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.
This is demonstrated in the picture below: the four phases are as seen:
There is no energy through the rectum and no risk of cold spots between discrete sonications. Dr. Laurence Klotz (Toronto, Ontario, Canada) 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 TACT study is a pivotal study of the safety and efficacy of whole-gland ablation for patients with localized prostate cancer.
Study Design:
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 were considered for inclusion. The accrual goal was 110 men, but they exceeded their accrual expectations.
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.
Outcomes:
They have accrued 115 men from 13 institutions.
- Median (IQR) age was 65 (59-69) years
- PSA 6.3 (4.6-7.9) ng/ml
- Pre-treatment, 72 of 115 (63%) men had Grade Group 2 (GG2) and 77 (67%) had NCCN intermediate-risk disease
In terms of safety and tolerability, Grade 3 adverse events occurred in 9 (8%) men, including infections (4%), urethral stricture (2%), urinary retention (2%), urethral calculus and pain (1%), and urinoma (1%), all of which resolved. There were no rectal injuries or Grade ≥ 4 events.
As for the primary endpoint of PSA reduction ≥75%, it was achieved in 110 of 115 (96%), with median (IQR) PSA reduction of 95% (91-98%) and nadir of 0.34 (0.12-0.56) ng/ml. Median perfused prostate volume decreased from 41 to 4 cc. Waterfall plot of PSA decline is seen below:
Stratified by disease aggressiveness and looking at 1-year biopsy results (10-core biopsy with a high density sampling as the prostate median volume after treatment was 4 cc), among 68 men with pre-treatment intermediate-risk GG2 disease, 54 (79%) were free of GG2 disease on one-year biopsy. Of 111 men with one-year biopsy data, 72 (65%) had no evidence of any cancer. Full biopsy results summarized below:
In terms of functional outcomes, of 112 men with one-year continence data, only 1% were incontinent (defined as >1 pad/day), while 4% reported increased daily leakage and 8% wore a pad. Median IPSS was unchanged at one year, from 6 to 6 (n=105). At one year, 20% of patients had Grade 2 erectile dysfunction, median (IQR) change in IIEF-5 was -3 (-13 to 0, n=105), and 69 of 92 (75%) maintained erections sufficient for penetration (IIEF Q2 ≥ 2).
On multivariable analysis, predictors of GG2 at one year included presence of intraprostatic calcifications at screening, MRI thermal coverage of target volume, and PIRADS ≥ 3 lesion at one-year post-treatment MRI (p < 0.05).
Based on these very promising results, the authors note that the TACT pivotal study of MRI-guided transurethral ultrasound whole-gland ablation (TULSA) in men with localized prostate cancer met its primary endpoint of ≥ 75% PSA reduction in 96% of patients with low rates of severe toxicity and residual GG2 disease. This may be an alternative option to definitive primary therapy for a subset of patients. As with other local therapy options, significantly more data and long-term outcomes are necessary – including information on salvage options.
Presented by: Scott Eggener, MD, Chicago, IL
Co-authors: David Penson, Christian Pavlovich, Joseph Chin, Steven S. Raman, Michael Koch, Jurgen Futterer, James Relle, Gencay Hatiboglu, Aytekin Oto, Yair Lotan, Axel Heidenreich, Marc Serrallach, Allan Pantuck, Sandeep S. Arora, Katarzyna Macura, Temel Tirkes, Daniel Costa, Gregory Zagaja, Thorsten Persigehl, J. P. Michiel Sedelaar, William Li, Robert Staruch, Mathieu Burtnyk, David Bonekamp, Masoom Haider, Laurence Klotz
Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois