MRI before biopsy better than TRUS

Monday, March 26, 2018 5:03:00 PM

COPENHAGEN, Denmark — The standard of care for diagnosing prostate cancer is set to change because of results now published from a head-to-head comparison of two different approaches.

The study, known as Prostate Evaluation for Clinically Important Disease: Sampling Using Image-Guidance or Not? (PRECISION), was conducted in 500 men for whom there was suspicion of prostate cancer, based on elevations in the levels of prostate-specific antigen (PSA) and/or abnormal results on digital rectal examination (DRE).

The results show that multiparametric MRI followed by targeted biopsy performed only on patients whose scans were positive detected more clinically significant prostate cancer and less clinically insignificant prostate cancer than the standard approach of 10- to 12-core transrectal ultrasonography-guided biopsy (TRUS), and it did so with fewer biopsy cores.

The findings were presented here during the European Association of Urology (EAU) 2018 Congress and were simultaneously published online March 19 in the New England Journal of Medicine.

"In 2012, we set out to try and design a study in which we compared the standard of care to a pathway involving MRI so that we could change that standard of care," lead author Veeru Kasivisvanathan, MD, University College London, United Kingdom, told delegates here.

"And we found that in biopsy-naive men with a clinical suspicion of prostate cancer, a diagnostic pathway involving prebiopsy MRI risk stratification with MRI-targeted biopsy is superior to 10- to 12-core TRUS biopsy," he emphasized.

"In men who need to have investigation for prostate cancer for the first time, PRECISION shows that using an MRI to identify suspected cancer in the prostate and performing a prostate biopsy targeted to the MRI information leads to more cancers being diagnosed than the standard way that we have been performing prostate biopsy for the last 25 years," he added in a statement.

"While I still think there is a role for systematic biopsy in some men in whom we still have some concerns, this is an incredibly important, practice-changing study, and we need to fast-forward MRI to the diagnostic pathway prior to biopsy," commented Declan Murphy, MB BCh, director of genitourinary oncology, Peter MacCallum Cancer Center, Melbourne, Australia, who acted as discussant for the study at the meeting.

It has been estimated that if high-quality MRIs can be introduced across Europe, more than a quarter of the one million men who currently undergo a biopsy could safely avoid it.

The PRECISION trial involved 500 men who had not previously undergone a biopsy of the prostate. The patients were referred because either their PSA level was abnormal (≤20 ng/mL), or they had an abnormal result on digital rectal examination, or both 

The Prostate Imaging-Reporting and Data system, version 2 (PI-Rads v2) was used to categorize areas suggestive of prostate cancer. A score of 1 or 2 designated a negative MRI; a score of 3 was considered equivocal with respect to the likelihood of the area being cancerous; a score of 4 indicated that prostate cancer was likely; and a score of 5 indicated that prostate cancer was highly likely.

If the MRI was negative, men could avoid undergoing a biopsy. "This is the first trial in which men who have a negative MRI have had a chance to avoid biopsy altogether," Kasivisvanathan noted.
If the biopsy was positive, men underwent a targeted biopsy only, thereby avoiding systematic biopsy, he added.

"The primary outcome was the proportion of men with clinically significant cancer, defined as a Gleason 3+4 or greater," Kasivisvanathan observed, "while important secondary outcomes included the proportion of men with clinically insignificant cancer, Gleason grade 3+3."

Results showed that for 28% of men who were randomly assigned to the MRI arm, MRI scanning was negative (PI-RADS v2 score ≤2 ). These patients did not undergo biopsy.
"Among the participants who underwent biopsy, a median of 4 biopsy cores were obtained...compared with a median of 12 cores in the standard-biopsy group," the team reported.

Clinically significant cancer was detected in 38% of the MRI-targeted biopsy group compared with 26% of the TRUS group, a difference between the groups that was significant (P = .005).

Furthermore, fewer men in the MRI-targeted group had clinically insignificant cancer, at only 9%, compared to 22% in the TRUS group, a difference between the two groups that was again significant (P < .001).
Kasivisvanathan pointed out that the proportion of cores that were positive for cancer was also much greater in the MRI arm, at 44% for the group that underwent MRI-targeted biopsies vs 18% for the standard-biopsy group.
At 30 days, patients who underwent an MRI-targeted biopsy reported fewer complications than the TRUS group. Complications included blood in the urine (30% for the MRI-targeted biopsy group vs 63% for the TRUS group); blood in the semen (32% vs 60%); pain at the procedural site (13% vs 23%); rectal bleeding (14% vs 22%), and erectile dysfunction (11% vs 16%).
ivisvanathan observed that the more favorable complication profile seen in the MRI arm reflected the fact that fewer men had to undergo biopsy at all, and for those who did, fewer cores were required for the diagnosis of prostate cancer.
Senior author Carole Moore, MD, University College London, the United Kingdom, commented that not having to undergo a biopsy and not receiving a diagnosis for insignificant cancer are both "huge advantages" in favor of the MRI risk-stratification approach.
"First of all, men miss out on the discomfort and the worry associated with biopsy," she told Medscape Medical News.
The other bonus of not receiving a diagnosis of cancer, even if it is "insignificant," is that it is better psychologically overall for patients.
"We know these indolent cancers are never going to cause trouble, but we also know that some people are nervous about hearing they have cancer and choose treatment anyway, which can be impactful in terms of erections and urine leakage and so on," Moore elaborated.
"So to test negative is a huge advantage, and the rate of indolent cancer was less than half in the MRI arm in the study than in the TRUS arm, which is a big advantage," she emphasized.
Practice-Changing Study

In his formal discussion of the study, Murphy said that PRECISION is "a truly-practice changing study" that will fundamentally transform the standard TRUS biopsy approach to the early detection of prostate cancer.

"I would also propose to you that this is very good news for our patients," Murphy added.

Not only are a significant proportion of men able to avoid biopsy altogether, but when they do require a biopsy, "there is much less core involvement, therefore fewer complications [while at the same time], more significant cancer — and less insignificant cancer — is diagnosed," he emphasized.

Murphy did point out that all men whose MRI results are negative prior to undergoing a biopsy may not be at uniformly low risk. Such patients have a 1 in 4 chance of having Gleason pattern 4 cancer on biopsy, and a Gleason pattern 4 signifies a higher-grade component to the tumor.

"The take-home message is, I think we have heard a new paradigm today, and we should embrace it," Murphy said.
"So I would agree that everyone should have an MRI if possible, and I now believe that in those patients with visible lesions, we can afford to only target the lesion as well," he added.

Commenting on the new results, Prof Hein Van Poppel, EAU adjunct secretary general, University Hospitals of the Leuven, Belgium, said in a statment: "This is a significant study. Prostate cancer can only really be confirmed by a biopsy, which is invasive and, like almost all medical procedures, carries some risk of side effects. Of course, in the majority of men who have a biopsy, no cancer is found. This work shows that using MRI to decide whether or not to perform a biopsy has the potential to save around a quarter of a million European men each year from going through the biopsy procedure, and so may be cost-effective in the long run. MRI use also shows up small, aggressive cancers at a curable stage and allows us to delay or simply not perform biopsies for some cancers which will not turn out to be dangerous. We need time to digest the study, but at first reading, it looks like it has the potential to change clinical practice."

The study was funded by the National Institute for Health Research and the European Association of Urology Research Foundation. The investigators and Dr Murphy have disclosed no relevant financial relationships.
European Association of Urology (EAU) 2018 Congress. Presented March 19, 2018.