MRI-Guided TULSA Shows Efficacy in Prostate Cancer

CHICAGO — The novel approach of MRI-guided transurethral ultrasound ablation (TULSA) shows efficacy in the treatment of localized prostate cancer that can be performed on an outpatient basis, inducing substantial reductions in prostate-specific antigen (PSA) as well as prostate volume over 12 months.

"This is a paradigm-changing treatment that is rapid and noninvasive, with potentially high efficacy and low side effects," study coauthor Steven S. Raman, MD, professor of radiology and urology, University of California at Los Angeles, told Medscape Medical News.

"It's an example of technology that is disruptive and requires disruptive thinking," he said.

In presenting on the 12-month findings from the TULSA-PRO Ablation Clinical Trial (TACT) study here at the Radiological Society of North America (RSNA), Raman reported that TULSA was effective in the overall elimination of clinically significant cancer in 79% of patients, with serum PSA declining by a median of 95%.

The new approach is one of many innovations in the field, as companies seek to create alternatives to current approaches. The limitations of standard treatment of prostate cancer with surgery and radiation include the risk of side effects such as impotence and bowel dysfunction.

The TULSA method specifically utilizes a transurethral device (Profound Medical, Inc) with 10 ultrasound-generating elements that can cover the entire prostate gland.

Using a software algorithm and MR guidance, precise doses of ultrasound waves are delivered to diseased prostate tissue while sparing healthy nerve tissue around the prostate.

The treatment is approved for clinical use in Europe and received US Food and Drug Administration (FDA) 510(k) clearance in August for the indication of prostate tissue ablation in the US.

The RSNA presentation is similar to data presented on TULSA earlier this year at the annual meeting of the American Urological Association.

TACT Study 12-Month Outcomes

The TACT study, which took place at 13 sites, included 115 men with localized prostate cancer with a median age of 65 (59-69) years. Among them, 67% had intermediate-risk and 33% had low-risk prostate cancer. Their median PSA was 6.3 (4.6-7.9) ng/mL.

Prior to TULSA treatment, 63% of the men had Grade Group 2 (GG2) disease, and 85% had a PI-RADS v2 score of 3 or more lesions, while 67% had 4 or more lesions.

The median ablation time was 51 minutes, with MRI showing 98% thermal coverage and an ablation precision of about 1.4 mm.

After 12 months, the study met its primary endpoint, with most of the men (96%) achieving a PSA reduction greater than 75%, with a median reduction of 95% and a nadir of 0.34 ng/mL.

Raman noted that the PSA reductions were seen within 3 months.

"The PSA dropped dramatically in 3 months, from an average of over 6 to less than 0.1," he said.

Median perfused prostate volumes were shown on MRI to decrease from 39 cc to 3.8 cc after the 12 months.

Among the 68 patients with baseline GG2 disease, 54 (79%) were shown on biopsy at 12 months to have elimination of GG2 positivity, and 65% were free of any disease.

Among 98 men with PI-RADS v2 score above 3 at baseline, 26 had MRI lesions at 12 months, including 11 with biopsy-confirmed GG2 (negative predictive value, 93%).

Factors found on multivariate analysis to be predictors of residual GG2 disease included intraprostatic calcifications at screening, MRI thermal coverage of target volume, and a PI-RADS v2 score greater than 3 at 12 months.

Safety Outcomes Encouraging

In terms of safety, 7.8% of patients experienced grade 3 adverse events, including 5 infections, 2 reports of retention, 2 stenosis, 1 bladder pain, 1 urethral calculus, and 1 urinoma, all of which resolved. There were no rectal injuries, rectal fistulas, or grade 4 events.

At 12 months, urinary incontinence was reported in 2.6% of men, with no severe cases. There were no changes in International Prostate Symptom Scores (IPSS) or EPIC bowel function.

In terms of erectile function, 75% of patients who were potent at the beginning of treatment regained their potency at 12 months.

"That is a much better rate than [other treatment modalities]," Raman said.

And there are other benefits. TULSA can be used in the treatment of diffuse and localized prostate cancer as well as in noncancerous conditions such as benign prostatic hyperplasia.

A Paradigm Shift, and Other Challenges

Raman explained that the TULSA approach challenges the current paradigm in prostate cancer treatment, in which urologists typically perform surgery and radiational oncologists perform radiation treatment.

"[The TULSA approach] requires radiologists and urologists to work together to achieve an excellent outcome, and both sides have to adjust to that treatment shift," he said.

Another challenge is in the learning curve and adapting to an approach utilizing MRI.

"Any time you involve MR technology, it can become more cumbersome and that could be a barrier in its adoption beyond larger academic centers and some practices," Raman said.

An additional hurdle could be in terms of reimbursement, which has been a challenge with other imaging-guided treatments as well, including laser technologies.

Importantly, however, the ability to perform the procedure on an outpatient basis significantly helps offset costs, Raman noted.

"The whole gland is instantly treated, and we anticipate treating only once. The results are pretty instantaneous," he said. "Patients are not required to stay in the hospital unless they have another problem, so that really is a benefit."

The TACT study is ongoing, and patients will be followed for up to 5 years, Raman said.

Further Comparisons, Larger Cohorts Needed

In commenting on the research, Vinay A. Duddalwar, MD, professor of clinical radiology and medical director of imaging services at the USC Cancer Center in Los Angeles, California, noted that the improved precision in ablation is an important benefit of the TULSA method.

"This allows changes and tweaks to the ablation during the process [and] I believe is an advantage compared to other primarily user-guided techniques," he told Medscape Medical News.

Duddalwar noted that, outside of the actual MRI time, the duration can still be lengthy.

"The procedure is still long — requiring anywhere from 3 to 4 hours of procedure time, including non-MRI time — so the eventual cost effectiveness will have to be weighed in," he said.

"We also cannot as yet compare the eventual results to other trials," he added. "This is early in the trial [stage], so we look forward to lengthier follow-ups in a larger cohort of patients."

Daniel Margolis, MD, an associate professor of radiology and director of Prostate MRI at Weill Cornell Medicine in New York, agreed that longer-term results will be anticipated, particularly as a result of inconsistent ultrasound results.

"The effects as described by the authors show promising early results, but this study focused on safety and technical adequacy," Margolis told Medscape Medical News.

"How patients do long-term is unknown," he said. "Ultrasound-guided treatments have variable efficacy, but many have significantly higher rates of residual or recurrent cancer."

A key advantage, however, is the rapid recovery, Margolis said.

"Some men may require a Foley catheter," he said, "but generally, the symptoms from the treatment are minimal and the recovery is much faster than for robotic surgery.

"However, larger prostates and prostates with calcifications, which are common in older men, may not be amenable to this technique."

The study was funded by Profound Medical, Inc. Raman is a consultant for Profound Medical but has no financial interests with the company. Duddalwar has disclosed no relevant financial relationships. Margolis has consulted for Blue Earth Diagnostics, which markets a PET tracer for detection of metastatic disease, and Weill Cornell is a recipient of a research grant from Siemens Healthineers.

Radiological Society of North America 2019 Annual Meeting: Abstract SSC07-07. Presented December 2, 2019.

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