Laurence Klotz, MD, FRCSC, reveals the impact of micro-ultrasound on his prostate cancer practice

Results from the OPTIMUM trial (NCT05220501) have established that microultrasonography-guided biopsy is noninferior to MRI/conventional ultrasonography fusion-guided biopsy for detecting clinically significant prostate cancer in biopsy-naïve men, offering a faster, more accessible in-office alternative to the current standard of care.

The results were presented at the European Multidisciplinary Congress on Urological Cancers in Prague. The findings were also previously presented at the European Association of Urology (EAU)’s Annual Meeting in March 2025 and concurrently published in JAMA.¹

The data represent what investigators describe as a defining milestone for the technology, which has already transformed the busy prostate cancer practice of Laurence Klotz, MD, FRCSC, professor of surgery at the University of Toronto and Sunnybrook Chair of Prostate Cancer Research, who spoke in depth with Urology Times about the technology.

Background and context

Microultrasonography has been available for roughly a decade, but until now has lacked the level of evidence needed to challenge MRI's dominance in prostate cancer imaging.

"There were a number of registry studies and comparative nonrandomized comparative studies where patients had MRI and micro-ultrasound, and they all showed pretty much the same thing—which is that the diagnostic accuracy of micro-ultrasound for significant cancer was comparable to MRI. [OPTIMUM] was an investigator-imitated trial to try and develop level 1 evidence for micro-ultrasound as a diagnostic imaging study compared with MRI,” Klotz told Urology Times.

The contrast in the existing literature between the 2 modalities is stark.

"MRI has been around for [approximately] 20 years or so, and widely used for close to 15 years. There must be at least 5000 on MRI in the prostate. There's about 100 papers on micro-ultrasound," Klotz noted. "So it's much more recent technology."

Klotz was candid about the significance of MRI's current role.

"MRI has been a game-changer. It's transformed the world of prostate cancer diagnosis. It's really a standard of care in most places—the response to an elevated PSA is MR imaging followed by, in most cases, a targeted biopsy."

Study design and population

The open-label, multinational OPTIMUM study enrolled 802 men with clinical suspicion of prostate cancer across 20 international sites in Europe, the United States, and Canada. Patients were randomly assigned across 3 arms: microultrasonography alone via the ExactVu micro-ultrasound platform (n = 137), MRI/conventional ultrasonography fusion-guided biopsy (n = 402), or a combined microultrasonography/MRI approach (n = 263). Baseline characteristics were well balanced across all 3 arms.

The unequal group sizes were deliberate.

"The rationale, frankly, was scientific humility," Klotz explained. "It really wasn't known whether micro-ultrasound was as good as MRI. And if it wasn't, it meant we were only exposing a sixth of the patients in the study to the inferior imaging modality. So, it was kind of a move to reduce the potential harm to the patients in the study."

The trial was originally designed to enroll approximately 1200 patients, with a prespecified interim analysis and stopping rule.

"If non-inferiority was demonstrated at the time of the interim analysis, the study would be stopped," Klotz noted. "That's essentially what happened." By the time the interim analysis was completed, 802 patients had been enrolled and non-inferiority had been clearly established.

In the combined arm, patients received MRI followed by microultrasonography, with the radiologist blinded to MRI findings until after the ultrasound target had been identified and biopsied.

Key outcomes

Clinically significant prostate cancer, defined as grade group 2 or higher, was detected in 47.1% of patients in the microultrasonography arm, 42.6% in the MRI/conventional ultrasonography arm, and 46.9% in the combined microultrasonography/MRI arm. The study met its primary end point, demonstrating non-inferiority of microultrasonography vs MRI fusion-guided biopsy (46% vs 43%; difference, 3.52%; 95% CI, −3.95% to 10.92%; noninferiority P < .001).

"The results really could not have been clearer," Klotz said. "There was actually a 4% higher rate of significant cancer diagnosed in the micro-ultrasound arm than in the conventional arm. Because it was a non-inferiority study, that wasn't a significant difference. It didn't change the interpretation.”

Detection of grade group 3 or higher cancer was also consistent across all 3 arms, at approximately 20%, as were targeted biopsy-only detection rates: 38.0% in the microultrasonography group, 34.1% in the MRI/conventional ultrasonography group, and 40.3% in the combined group. There were no significant differences between arms in grade group 1 cancer detection. Notably, results were also consistent across participating sites.

"It's not like there were sites who had dramatically different results compared to the median performance of the sites. It was fairly consistent," Klotz said.

Imaging characteristics and lesion visibility

Klotz described where microultrasonography performs best and where its limitations lie.

"The strength of the micro-ultrasound is visualization of the near prostate, particularly the peripheral zone, which is normally very homogeneous," he said. Anterior visualization can be more challenging, particularly in patients with significant calcifications. "They can cause shadowing and obscure visualization of the more transition zone. But practically speaking, 70% of prostate cancers are in the peripheral zone. And in the average patient, you can see almost all of the prostate at the highest resolution."

He also noted that the 2 modalities detect partially overlapping but not identical sets of lesions.

"There are patients who have a lesion seen on ultrasound that's invisible on MRI, and vice versa. It's somewhere around 15% to 20% each." He acknowledged this raises the question: "What are the molecular aberrations that would result in visibility on one imaging modality and not the other? But that's another topic."

Prostate volume did not appear to compromise microultrasonography performance.

"There was a quite a substantial range in prostate volume, but the data did not show any trends for, for example, worse performance of the micro-ultrasound with larger prostates. Not at all," Klotz said.

Workflow and accessibility

Beyond efficacy, Klotz emphasized the practical advantages of microultrasonography in clinical practice.

The procedure, Klotz said, “takes maybe 5 to 10 minutes. And then another 5 minutes or so for the biopsy," he said. "It's very appealing to the patients to come in—one-stop shopping. They just come in, have the procedure, the diagnosis and the biopsy all at the same time."

He also described the patient experience more specifically.

"I generally only do targeted biopsies, usually 3 cores per target, so maybe 3 to 6 cores is the average depending on how many targets. I use transperineal technique. It's quick." He added that an inhaled analgesic called Penthrox has made the transperineal approach more comfortable for patients.

"It really makes the transperineal biopsy easy for the patient."

Klotz noted that the environmental footprint of the approach also drew attention following publication.

"One of the responses to this paper when it was published referred to the carbon sustainability feature—that with one-stop, less travel back and forth, less utilization of the MRI, which is quite carbon intensive."

The learning curve, while real, is manageable for experienced ultrasonographers.

"For practitioners who are experienced doing conventional ultrasound, the learning curve is only something like 20 to 25 cases to develop basic competence at recognizing the lesions," Klotz said. "And there are now some very good online modules where you can fast-track that learning curve quite readily."

With experience, lesion recognition becomes intuitive.

"After a year or so of doing this, the lesions just jump out at you. It's like looking at a car headlamp at night. It is so obvious that there's a lesion there." He added that longer experience also teaches restraint: "You learn also what lesions you don't need to biopsy…You may see a 2-mm suspicious lesion—there's probably no benefit to biopsying something that small."

Access, cost, and competitive landscape

Klotz highlighted the technology's value in MRI-constrained settings.

"In Canada particularly, we are MRI resource squeezed. It can take a number of months to get an MRI on a patient with an elevated PSA. This facilitates the whole thing." He estimated that roughly 60% of his patients no longer require MRI to reach a diagnosis or management decision.

Cost is a significant differentiator; Klotz said the cost of microultrasonography is “something like 10% of [MRI].”

"The maintenance costs and so on are very trivial compared with MRI. You don't need a full-time technologist running the machine,” he added.

Currently, only one manufacturer produces the technology.

"There is no other high-resolution micro-ultrasound system out there that I'm aware of," Klotz noted. "Will there be another one at some point? I have no doubt. But at this point, Exact Imaging is the sole provider."

Role in active surveillance and difficult cases

Klotz described how microultrasonography has become embedded in his active surveillance program.

"We have now approaching 2000 patients being followed in active surveillance. My standard approach is to alternate micro-ultrasound with MRI, each one every 4 years. So they're getting reimaged every 2 years, but alternating those 2 modalities."

He also discussed its utility in the clinically challenging PI-RADS 3 population.

"What do you do with PI-RADS 3, biopsy or not? There are data that when the micro-ultrasound is negative with PI-RADS 3, that has 100% negative predictive value for significant cancer. So it allows you to rationally manage these patients who otherwise are a conundrum."

When microultrasonography yields a negative result in higher-risk patients, Klotz does not abandon further work-up.

"If the imaging is negative, they're not sent out into the wilderness. They're back in a year. We reassess the situation, maybe do the alternate imaging.”

Clinical implications

Klotz summarized the technology's impact on his own practice concisely.

"Elevated PSA now goes straight to micro-ultrasound. If the micro-ultrasound is negative, most of the time we stop—unless it's a really high-risk patient. If the ultrasound shows a lesion, we do the biopsy."

"These results are a game-changer for urologists and patients," he concluded in a news release. "We now have an in-office diagnostic tool proven non-inferior to MRI that is easy-to-use, affordable, and speeds the diagnosis process. I believe the technology has the potential to improve standard of care and reduce care disparities, especially for those with limited access to MRI."²

REFERENCES

1. Kinnaird A, Luger F, Cash H, et al. Microultrasonography-guided vs MRI-guided biopsy for prostate cancer diagnosis: The OPTIMUM randomized clinical trial. JAMA. 2025;333(19):1679-1687. doi:10.1001/jama.2025.3579

2. Micro-ultrasound proven non-inferior to MRI for prostate cancer diagnosis in OPTIMUM randomized trial. News release. Exact Imaging. November 19, 2025. Accessed November 19, 2025. https://www.businesswire.com/news/home/20251119703366/en/Micro-ultrasound-Proven-Non-Inferior-to-MRI-for-Prostate-Cancer-Diagnosis-in-OPTIMUM-Randomized-Trial