Refining Focal Radiotherapy Practice with HIFU in Prostate Cancer

The emergence of high-intensity focused ultrasound (HIFU) corresponds with a significant shift toward focal management in the prostate cancer treatment paradigm, aiming to bridge the gap between active surveillance and radical intervention. In a recent dialogue with CancerNetwork®, Mina Fam, MD, highlighted how successful patient selection relies heavily on multiparametric MRI to identify well-defined index lesions along with genomic testing as a critical safety check for risk stratification.

Technological advancements in robotic platforms now allow for real-time ultrasound fusion and stepwise energy delivery. This intraoperative precision may help navigate variables such as prostatic edema and ensure the preservation of surrounding healthy tissue. While long-term longitudinal data are still maturing, HIFU has demonstrated a favorable adverse effect (AE) profile, particularly regarding the preservation of urinary continence and erectile function compared with robotic-assisted radical prostatectomy. Furthermore, it offers reduced bowel toxicity relative to ultra-hypofractionated radiation therapy.

For post-ablation surveillance, clinicians must utilize expert radiologic assessment to differentiate treatment-induced fibrosis from nodular recurrence using multiparametric MRI or PSMA-PET. Although prior ablation can distort anatomical planes and induce scarring, salvage therapies remain a viable and safe option. Ultimately, the integration of advanced imaging and genomics facilitates a tailored approach, minimizing overtreatment while prioritizing patient quality of life.

Fam is the medical director of Urologic Oncology at Jersey Shore University Medical Center and of Robotic Surgery at Ocean University Medical Center, as well as a urologic oncologist in the Hackensack Meridian Health system.

CancerNetwork: Beyond Gleason score and prostate-specific antigen (PSA) levels, what specific imaging characteristics or genomic markers do you look for to determine if a patient is a candidate for focal HIFU therapy rather than active surveillance or radical intervention?

Fam: In terms of imaging, the multi-parametric MRI is the mainstay of how we determine if a patient’s a candidate for HIFU focal therapy. What we’re looking for is a well-defined MRI-visible lesion that’s consistent with the area of biopsy-proven cancer. That allows us to treat an area focally with HIFU and good confidence that we’ll be able to treat the higher-risk or index lesion and make sure that that therapy has good oncological outcomes.

In terms of genomic testing, I use it as more of a safety check to determine whether my patient is a good candidate for focal therapy. Let’s say you have a patient who you think is good candidate for focal therapy, but you get a genomic marker that may say the patient’s at a higher risk than you believed. That patient may be counseled that they have a higher risk of recurrence or a higher risk of needing salvage therapy, and they may elect for doing more whole-gland therapy, such as surgery or radiation. By the same token, if the patient is on the fence of whether to be on surveillance vs receiving focal therapy or more advanced therapy, the genomic test can help guide us towards surveillance vs one of those therapies.

How do you distinguish between post-ablation fibrosis and potential recurrence on follow-up multi-parametric MRI or PSMA-PET scans?

In terms of patients who’ve had HIFU focal therapy, we usually see, on a subsequent MRI, volume loss or a linear scar on t2 imaging, and that’s suggestive of fibrosis. What is more worrisome for recurrence is a nodular focal area where it enhances or has diffusion restriction, like you would see on an MRI prior to treatment. That is more concerning for recurrence.

If the MRI is equivocal and you’re not quite sure, or the PSA is going up and down and you’re not sure, then you can use a PET-PSMA and see if there is PSMA activity in the area, which would suggest a biologically active disease. The main thing is, we rely on our radiology colleagues to accurately look at these images and give their expert opinions on them.

How does the adverse effect profile of HIFU specifically compare with contemporary nerve sparing, robotic-assisted radical prostatectomy, or ultra-hypofractionated radiation therapy in terms of long-term patient-reported outcomes?

The first caveat I’ll mention is that the data for focal HIFU therapy are [smaller] in terms of the follow-up at this point in time, whereas surgery and radiation treatments have several decades of follow-up. That being said, in terms of comparing focal HIFU to surgery, there are better continence and better erectile function outcomes because you’re only treating a portion of the prostate vs the whole prostate.

When it comes to radiation—specifically, hypofractionated radiation—there is less bowel toxicity with the HIFU focal therapy compared with stereotactic body radiation therapy [SBRT]. Again, the data are still maturing, and we are looking to see more long-term longitudinal follow-up on focal therapy.

During the procedure, how does the technology account for intraoperative variables such as prostatic edema to ensure that the targeted thermal energy remains precisely on the tumor?

The technology we’re using is a robotic platform where you can make fine adjustments intraoperatively. But in terms of the planning stage, we use the MRI and re-fuse with the real-time ultrasound. We’re able to do a targeted map of our lesion in 3D. Then, we use the real-time ultrasound and deliver the treatments in a stepwise fashion, meaning the energy is delivered in segments. We’re also monitoring that real-time ultrasound to check for edema and any potential damage of surrounding structures, which we would want to avoid. We’re constantly making adjustments during the treatment time to ensure that none of the healthy tissue we want to preserve are damaged [through] focusing on the target in real-time ultrasound.

In the event of a local recurrence, what technical considerations should radiation oncologists or surgeons be aware of regarding the tissue microenvironment of a previously ablated prostate when planning salvage therapy?

Focal therapy can cause a distortion of the anatomy. It does cause fibrosis and can cause the tissue planes for surgery to be much more different than someone who hasn’t had prior focal therapy. It’s important for the radiation oncologist to keep in mind how they plan their dosing for the urethra or near the rectum after a focal therapy case, and for a surgeon to be careful of fibrosis, scarring, and distorted planes. The good news is that salvage treatment is feasible, successful, and safe, but [we] obviously understand that [having] someone with more experience and a thoughtful approach to the treatment is important.

What are some noteworthy sessions that you will either be attending, or perhaps even presenting, at the 2026 American Urological Association (AUA) Annual Meeting?

I am interested in sessions that look at the combination of focal therapy with imaging, with genomic testing, and the intersection of all those in helping determine the best treatments for patients who are interested in focal therapy. Also, [I am] looking at patients who receive focal therapy and what salvage treatments and strategies we can employ [for them]. Those are the things that I’m looking forward to help guide my practice and help me navigate the future of focal therapy.

What other advances in radiation or surgical oncology do you believe have the potential to transform practice in genitourinary cancers?

This space of focal therapy has been a great advance in the treatment of prostate cancer. We’re tailoring treatments to [be] more focal and more focused to avoid overtreatment. In terms of radiation oncology, there’s been a lot of great successes and advances in PSMA-PET scanning, which has allowed for radioligand therapies and more targeted radiation treatments. [There is] also the use of MRI and more adaptive radiation, where we can limit damage to surrounding structures, so that [during] whatever treatment we are pursuing—whether it’s surgery, focal therapy,or radiation—we can limit the damage to surrounding tissues and preserve quality of life for patients.