Could a 'Manogram' Replace a Prostate Biopsy?

Look First, Then Biopsy

Neil Osterweil

August 01, 2019

Could imaging replace a painful biopsy in testing for prostate cancer?

Such is the vision of Jelle Barentsz, MD, PhD, from the Radboud University Medical Center in Nijmegen, the Netherlands, who recently presented data to support the use of a fast biparametric (bp) MRI technique for prostate imaging.

He positioned this as a first step in the workup for patients whose prostate-specific antigen (PSA) level is found to be elevated. Such imaging could spare men from the pain and complications of a prostate biopsy, at least in this first instance.

Barentsz proposed the term "manography."

This could make MRI of the prostate for men of a certain age as routine as mammography screening for breast cancer is for women of a certain age, he suggested.

"MRI can be fast, noninvasive, accurate, and potentially less expensive [than biopsies]," Barentsz said.

When I first learned about this as-yet unrealized promise of using MRI as a routine screening modality for prostate cancer, offering the tantalizing prospect of avoiding biopsies, I thought, "sign me up!"

I speak as a 62-year-old who has been lucky enough to have had three — count 'em, three — ultrasound-guided prostate biopsies, all of which, fortunately, came back negative.

Given my family history and my high-normal levels of PSA, I discussed it with my primary care physician, and we agreed that it made sense for me to "man up" and have the biopsies.

Looking for Trouble

Screening for prostate cancer with the PSA blood test was once widespread in the United States but is now controversial.

Concerns over potential harms from overdiagnosis of lesions that may never spread led to recommendations against routine use of the PSA test.

PSA itself is a notoriously fickle marker that can be affected by many different factors, such as sexual intercourse, exercise, and diet, as reported by Medscape Medical News earlier this year.

The US Preventive Services Task Force (USPSTF) issued a statement that is lukewarm at best regarding prostate cancer screening for men in my age group — 55 to 69 years. The statement reads, in part, as follows:

"In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening."

The statement doesn't fudge when it comes to older men, however: "The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older."

A Pared-Down MRI Method

Okay, I get it. Given my family history, I have a higher-than-normal risk for prostate cancer, and maybe an invasive procedure in my case isn't such a bad idea.

But what about others? Are there any prospects for a safe, reliable, and less invasive method for identifying men who may need further clinical scrutiny?

Barentsz and colleagues propose that the fast bp-MRI technique could offer such an approach.

The technique hinges on a pared down MRI method.

Currently established methods include multiparametric MRI, which involves T2-weighted images in three planes, plus diffusion-weighted imaging and contrast enhancement. It takes about 18 minutes.

There is also a biparametric MRI technique in which the contrast is omitted. This approach takes about 13 minutes.

The new technique that Barenstz and colleagues are using, fast bp-MRI, eliminates image acquisition in the sagittal and T2 coronal planes, and also skips the contrast. It takes only 8 minutes.

What Did I Miss?

Barentsz and coauthors admit, however, that the faster, potentially cheaper, noncontrast MRI protocols are also controversial, because it is uncertain whether they are as good as the more established MRI approaches in ruling out clinically significant prostate cancer.

This is also a concern expressed by other prostate cancer experts that, despite my hopes, MRI-based prostate cancer screening isn't up to snuff (yet).

For example, a urologic oncologist who was a coinvestigator of the PRECISION trial, which is investigating MRI with or without targeted biopsy, commented that he isn't quite ready to pull the trigger on MRI screening.

"I just don't think there's sufficient evidence to say that MRI is ready to be utilized as a screening tool," Samir Taneja, MD, from NYU Langone Health in New York City, said in an interview.

"The implication of a screening test is that it has reasonably good sensitivity and hopefully relatively few false positives," he said.

The problem is that the sensitivity of MRI for screening is not good enough as yet to give clinicians confidence that there will be no false negative results, potentially missing patients who should undergo further testing.

"The thresholds that we use to detect disease in PI-RADS [Prostate Imaging Reporting and Data System] are really established in a population of men who are already identified to be at high risk because of elevated PSA. So you can imagine that's a population of men in whom the prevalence of prostate cancer would be higher than a nonscreened population," he said.

On the Thresholds

In Barentz' study, investigators compared the diagnostic performance of contrast-enhanced multiparametric MRI (mp-MRI) with fast bp-MRI in the detection of clinically significant prostate cancer among 626 biopsy-naive men. All men underwent a prebiopsy enhanced mp-MRI on 3 Tesla MRI scanners.

Prior to biopsy, two blinded readers prospectively assessed the monoplanar fast bp-MRI, then the triplanar bp-MRI, and finally the mp-MRI images. Then, systematic transrectal ultrasound-guided biopsy was performed, and men with suspicious lesions (defined as PI-RADS 3-5) on mp-MRI additionally underwent MR-in-bore biopsy.

The sensitivity for prostate cancer for all protocols was 94.7%. The specificity of the fast bp-MRI was 65.4%, compared with 68.6% each for the more time-consuming biparametric and multiparametric scans.

However, 1% more insignificant cancers were flagged by fast bp-MRI.

Agreement between readers was 90.3% for the fast technique, compared with 92.7% for biparametric MRI.

Not So Fast

Ronald C. Chen, MD, from the Linenberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, said in an interview that "if we're able to reduce the cost of MRI for prostate cancer, that would be an important goal for physicians, for patients, and for healthcare payers.

"But even a full multiparametric MRI today is not perfect at detecting prostate cancer, and in fact there's good data suggesting that it misses some important cancers. So if a full MRI today misses some important cancers, you wonder if a cheaper, faster version would potentially miss more, and that needs to be studied," he said.

Barentsz told Medscape Medical News that although the direct costs of fast bp-MRI are 54% lower than those associated with multiparametric techniques, the total costs are a washout. The fast technique is associated with a 2% higher biopsy rate and 1% higher overdiagnosis rate (detection of insignificant prostate cancers), with associated costs that cancel out any current economic advantage for fast MRI, he admitted.

He also explained that in the Netherlands, prostate MRI costs approximately €500 ($567) less than TRUS-guided biopsy.

"In my country, we have about 40,000 men with elevated PSA annually, so for the healthcare it saves €20 million, " he said. "In the US, it is 1 million patients with elevated PSA who will have TRUS biopsy — potentially that is [a saving of] €500 million euros [$567 million] per year," he said.

Another prostate cancer expert echoed a maxim familiar to engineers: "You can have it fast, cheap, and good. Pick two."

"With the biparametric technique, without contrast enhancement, you can't get the neovascularity component of the tumor, and many believe that's important," said Julio Pow-Sang, MD, from the Moffitt Cancer Center in Tampa, Florida.

Where MRI Shines

Although experts appear hesitant regarding the use of MRI for screening and diagnosing prostate cancer, there is already an established use of MRI further down the line.

Robust data support the use of MRI for the management of men who have already been diagnosed with prostate cancer, and imaging technology can help men to get out of the "PSA screening web," according to Alexander Kutikov, MD, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania.

"I tell my patients that one of the biggest risks they face in this whole process is overdiagnosis of a low-risk cancer, a cancer that has a mortality rate of less than 1%, a cancer that actually puts them on the hook for care that has very little value but creates a lot of anxiety," he said in an interview.

"Right now, there's no way to put the genie back into the bottle once you find this low-risk cancer," he said in an interview.

MRI is invaluable both for reducing overdiagnosis of low-risk tumors and for providing accurate sampling when a biopsy is required, Kutikov said.

Insurers Balk at Coverage

However, when asked about the idea of using MRI for routine screening for prostate cancer, Kutikov replied: "I would say that right now in the United States, we need to fight a much bigger battle in actually being able to provide MRI coverage for our patients with elevated PSAs," he said.

"Insurers like Aetna and Cigna absolutely refuse to integrate the level 1 evidence from trials like PRECISION, where 28% of men did not have to undergo a prostate biopsy," he said.

In the PRECISION trial, 500 men for whom there was clinical suspicion of prostate cancer were randomly assigned to undergo either MRI with or without MRI-targeted biopsy or conventional transrectal ultrasound-guided biopsy. Of the 252 men assigned to MRI, for 71 patients (28%), MRI results were not suggestive of prostate cancer, and so the patients did not undergo biopsy.

But Kutikov also emphasized that Barentz' idea of MRI-based screening is aspirational rather than practical at the moment, because, as Taneja also pointed out, all of the data to date have come from studies of men who were first screened with PSA and whose screening results indicated a need for biopsy.

"It's a hard question to answer, but I think that at least on this continent, there's just not going to be a lot of enthusiasm for even venturing there, because the battle that a lot of us in this space are fighting now is to get our patients with elevated PSA covered for MRIs in the first place," he said.

Jon McConathy, MD, a radiologist at the University of Alabama School of Medicine in Birmingham, agreed that cost is a major barrier to the idea of manography.

"The contrast-enhanced part is probably not as important, especially if you're thinking about screening and finding men who need further workup, so I think there's real potential there," he told me.

"I think the challenges are that the cost of MRI is substantially higher than screening mammography, the large number of men with prostate cancer, and the fact that many of them don't need to be treated," he said.

"So the two missing pieces are how to make it work on a large scale economically and how to deal with the large numbers of low-grade prostate cancers that are going to turn up," he said.

Hope for the Beleaguered

So what's a man with a modestly high PSA — and nothing else — to do?

Kutikov told me, reassuringly, that another advantage to MRI is its ability to precisely measure prostate volume.

"If somebody's PSA is 3.6 [ng/mL] but their prostate volume is 60 [mL], then all of a sudden the PSA density is within normal limits; you basically can account for PSA elevation being caused by prostate volume," he said.

"You can tell these men you don't even need to get a PSA for the next couple of years. Get it again in 2 years, make sure it's not going up, and once you hit 70, no more PSA," he said.

McConathy pointed to one promising development that could reduce fruitless prostate biopsies: the use of new positron-emission tomography tracers that target prostate-specific membrane antigen.

"The idea is that you could use prostate MRI to identify suspicious lesions, and then there may be an additional noninvasive test you could do that might help you decide if you just need to watch this or if you actually need to do a biopsy," he said.

All physicians interviewed for this article and Barentz have disclosed no relevant financial relationships.

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