At the 2024 SIR Annual Meeting, Steven Raman, MD, University of California, Los Angeles, presented 5-year follow-up results on a trial evaluating MRI-guided transurethral ultrasound ablation (TULSA) among patients with localized prostate cancer.

These results showed durable oncologic control, safety, and functional preservation following a single whole-gland TULSA procedure.

In this interview with IO Learning, Dr Raman describes how TULSA is different, and similar, to other ablation processes, highlights the importance of quality-of-life outcomes for these patients, and discusses the key consideration when treating prostate cancer.

IO Learning: How is TULSA different from other types of ablation for prostate cancer?

Steven Raman, MD: It's similar to some things that exist now. For many years, you've had thermal technologies being used to treat prostate cancer. The oldest of those is cryoablation, which is freezing. And the next oldest is heat-based ablation in the form of high-intensity focused ultrasound (HIFU). What’s similar about TULSA is it's a heat-based technology, meaning that it's ultrasound waves leading to heating of tissues that it interacts with.

There are some important differences. Number one, instead of coming from the rectum, which is what most HIFU is about, it uses novel technology that arises from a device inserted into the natural cavity of the urethra and goes from the inside out. It’s not an outside-in technology, like these others. For cryoablation, we need needles to be inserted. typically that's transperineal, but it can also be transrectal. There can be many ways to insert a needle into the prostate. There are other technologies for heat that is laser fiber, either transrectally or transperineally. Also, there are other newer technologies like irreversible electroporation, that use electricity, but also require the placement of needles.

In that sense, TULSA is most like HIFU, but there are important differences. It's completely MRI-based. There are only 2 technologies that I know of that are completely MRI-based and that is TULSA and also the Insightec transrectal ultrasound system. That's also MRI-based and non-invasive. And cryoablation can also be done with MRI, at certain centers.

But the important thing is with MRI-guidance is you know exactly where the tumor and the tumor margins are. There's no guessing. And the other very important thing is that you can assess exactly where to treat. You know exactly where the margin of the prostate is, you know where the tumor is, you know where the margins of the tumor are, and you know where the nerves are, you know where the sphincters are. These are all very important safety measures to avoid any complications or side effects from these therapies, which can be substantial.

The most important and feared complications are impotence and incontinence or strictures leading to urinary problems. Those can all occur. Knowing where these margins are helps us avoid those kinds of problems, or minimize those kinds of problems.

One other really important thing about MRI-guidance that the other technologies lack is a safety issue, knowing exactly how hot to make it, how hot it gets at the margins. Both at the target and at the margins. When you're dealing with heat, you want it to be 60 degrees or more at the target. At the margins, you want it to be at least 50 degrees. And you don't want it to be heating more than about 30 to 40 degrees in areas that are sensitive. You don't want that margin to get much higher than about 40 degrees. And you can see all that during the treatment with MR thermometry. No other technology has that kind of safety margin. That’s what I really like about it: knowing where to treat, how to treat, and how hot to treat.

IO Learning: Are there any limitations to this technique?

Dr Raman: The biggest limitation is you need to be able to undergo an MRI. We assume most these men have had MRIs, because it's not going to work with people who can't undergo MRI.  

Also, most of these technologies, it's a case-by-case basis on what is paid for and what's not paid for. It’s not clear that these are covered by insurance. They are covered by Medicare, but they're not necessarily covered by insurance. It could be a cost barrier for sure, for all these things.

IO Learning: Please describe the trial you presented at the SIR Annual Meeting evaluating TULSA for localized prostate cancer.

Dr Raman: It’s a multicenter trial of 13 trials, which basically showed that over 5 years, 79% of men had no significant prostate cancer on a 1-year biopsy or any other evidence of rising PSA or anything else prompting a biopsy at 5 years. That is something that you see in other technologies, both in whole-gland radiation — This was whole-gland treatment. So it wasn't a focal treatment. Most of the time, these other techniques that I talked about, are focal techniques. You can also use TULSA as a focal technique, but this trial was treating the whole prostate gland.

What was good is there's a significant reduction in volume, like 90% reduction of volume of the prostate. And 70% of men had no evidence of prostate cancer at 5 years. About 20% had some biopsy-proven or other means of diagnosis for prostate cancer and a percentage of those men underwent additional treatments to deal with their prostate cancer.

No one we know of had metastasis. We were dealing with men who had primarily Gleason 3 and 4 or Gleason 2 disease and some Gleason 1 disease. This is intermediate-risk and then low-risk men. It wasn't really dealing with higher Gleason groups. But in those people, the outcomes are very good and comparable to both radiation and prostatectomy. Both of those have biochemical recurrences and other recurrences in the 20% to 30 % range. This was in that range.

The big difference was that the number of side effects was much lower, including impotence and incontinence or any urinary problems. Urinary problems were very low and the sexual dysfunction was around 20%. That that was a huge difference. Eighty-seven percent of men retained the ability to have sexual intercourse and had erections that were sufficient for penetration. That's the one marker of quality of life. They were able to do that.

Those are very compelling numbers because very few whole-gland technologies have those side effect numbers.

IO Learning: What are the future steps for this trial and other trials involving TULSA?

Dr Raman: There's going to be more trials. There’s one trial that is ongoing, called CAPTAIN, randomizing men to radical prostatectomy versus whole-grand TULSA, and that's happening as we speak. It's accrued about half its total number of patients.

And then a number of trials are planned for both focal therapy and other other focal therapy and other uses. Because you can imagine that there are a number of uses for technologies like this, after radiation failure, after recurrence what currents, after prostatectomy, and so on and so forth. But, the CAPTAIN trial is the closest to being completed.

IO Learning: What is the main takeaway for clinicians about this trial and TULSA?

Dr Raman: The whole issue with prostate cancer is not so much the technique, but the idea that, 10 or more years ago, there was no imaging in prostate cancer. Everything was done in sort of a blinded fashion. PSA was rising. When the PSA rose above the number 4, then that prompted a biopsy. But 70% of men who had a PSA >4 never have prostate cancer. And 30% of men have prostate cancer with a PSA >4. Prostate cancer is a very common cancer, 1 in 7 to 1 in 8 men get prostate cancer. The real question is separating the minnows from the sharks.

We need to have a process where we can identify the most aggressive cancers and not so much the fact that we just identify prostate cancer. Most men with prostate cancer, especially with low Gleason group grade, like 1 or 2, could probably undergo active surveillance.

The real question is when to treat and how to treat. Because in the past, with this strategy of PSA and systematic biopsy, we identified cancers and it significantly brought down the rate of death from prostate cancer, but it also resulted in lots of over-treatment. Between 1 and 2 million men were over-treated. And the problem with that, is poor quality of life, lack of ability to have sexual relations and having lots of urinary complications. It’s kind of a miserable quality of life when that happens.

MRI imaging, PSMA PET imaging have shown us where the cancers are, where the most aggressive cancers are and helped us now do targeted biopsies of those cancers. And hopefully that means we're finally identifying the sharks and then leaving the minnows alone.

Anything you do to prostate cancer is fine, as long as the person doing it is experienced and the side effect profile for that person is low. Operator dependence is a big issue. Who's going to do it? How are their outcomes? The tool is important, but the operator is even more important.

TULSA gives us another way to intervene. It's not a magic bullet, in the sense that it doesn't sort of somehow magically solve all these other problems. It's the same problems. It's another tool, another hammer in our tool belt. And it seems to be effective in these kinds of cancers at 5 years with a very favorable side effect profile. That presents another alternative to men, to have something done for those who need something done.

The bottom line is, there's a lot to work to be done in prostate cancer, to really nail down with imaging, with genomics and proteomics and informatics, artificial intelligence of all these other things, you know, which are the aggressive cancers and which aren't the aggressive cancers.

It may turn out in the future that maybe the imaging-based cancers aren't the most aggressive cancer. But for right now in 2024, as far as we know, imaging can help us pick out the most aggressive cancers.

Source:

Raman S, Arora S, Macora KJ, et al. Five-year outcomes after MRI-guided transurethral ultrasound ablation (TULSA) of localized prostate cancer. Presented at Society of Interventional Radiology Annual Meeting. March 23-28, 2024; Salt Lake City, UT