Combined MRI and Ultrasound Prostate Biopsy: 'Paradigm Shift'

Neil Osterweil

March 10, 2020

Combining MRI-guided biopsy of the prostate with conventional ultrasound-guided 12-core prostate biopsy was superior to either technique alone at ruling out more aggressive cancers, and beat MRI-guided biopsy alone at detecting clinically significant tumors in a National Cancer Institute study.

For 2103 men who underwent MRI-guided biopsy followed by a second, systematic biopsy, the combined approach led to a 10% increase in cancer diagnoses and a 22% increase in upgrading to a higher Gleason grade group than either technique alone, reported Michael Ahdoot, MD, from the Urologic Oncology Branch at NCI, and colleagues.

The study was published in the March 5 issue of the New England Journal of Medicine.

"Among patients with MRI-visible prostate lesions, the addition of MRI-targeted biopsy to systematic biopsy increased the detection of clinically significant cancers (grade group ≥3) and led to a net decrease in the detection of clinically insignificant cancers," the researchers noted.

"Although many of these benefits resulted from MRI-targeted biopsy alone, omission of systematic biopsy would have led to missing the diagnosis of 8.8% of clinically significant cancers," the investigators continued.

However, the combined technique is both time-consuming and technically complex, and may not be coming soon to a clinic near you, the authors acknowledged.

This study was conducted "at an institution where many practitioners were experienced in performing and interpreting prostate MRI and prostate histopathological analysis. These results may not be reproducible at institutions with less experienced practitioners," they comment.

Coauthor Minhaj Siddiqui, MD, now with the University of Maryland School of Medicine in Baltimore, tells Medscape Medical News that "there's definitely a learning curve to this approach, just like any new technology, really."

He added, however, that with time and experience, the accuracy of the combined technique when performed at other institutions will likely approach that of the results seen in the NCI study.

Has Revolutionized Diagnosis

Approached for comment, Eric Wallen, MD, a professor of urology at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, said that the combined technique has revolutionized diagnosis of prostate cancer, but agreed with the authors that the results require skilled interpretation.

"In this study, the MRIs were reviewed by expert radiologists," he noted. "They have the most experienced radiologists in the world looking at people's prostates, but it's important to realize that in community and in other academic centers as well, the way the MRI is done can vary widely; there's no industry standard for how to do the actual study, so the results are not valid or interpretable equally," he said.

In addition, there is wide disparity among radiologists, and in the skill sets of urologists who perform biopsies in the interpretation of results.

"We've seen variation across radiologists at our own institution, depending on who's reading the scan," Wallen acknowledged, "and then you have urologists, like me, who vary in their ability to use the software platform to hit the target accurately, so that's a really big deal."

He added, however, that many academic cancer centers, including his own, have results using the combined technique that equal or approach those accomplished by the NCI investigators.

"I think when this first began, people felt that if they did a really good MRI that they would only have to biopsy the target, but this study did not show that. This study showed that you still have to add the systematic biopsy to pick up cancers as well," Wallen said.

Alexander Kutikov, MD, chief of the division of urology and urologic oncology at the Fox Chase Cancer Center in Philadelphia, Pennsylvania, tells Medscape Medical News that the combined technique represents a paradigm shift in how prostate cancers are diagnosed, particularly in its ability to discriminate cancers that can be safely managed with observation.

"There are two deliverables to this technology," he said. "One, you're doing a better biopsy, basically minimizing underdiagnosis of clinically significant cancers. The second deliverable is that ideally you're minimizing overdiagnosis of Gleason 6 cancers that [if treated] can disrupt people's lives and arguably have very little value in being diagnosed."

Both Wallen and Kutikov said that the additional cores taken with the combined technique do not significantly contribute to excess morbidity or pain for the patient.

Would MRI Alone Suffice?

Previous studies have shown that MRI-targeted biopsies are better at detecting high-grade cancer than systematic biopsies, but the role of the MRI-guided approach — replacement for systematic biopsy or complement to it — is still unclear, the authors comment.

To that end, they conducted the current research as a substudy of the "Use of Tracking Devices to Locate Abnormalities During Invasive Procedures" study.  

They enrolled adult men 18 and older who had either elevated serum prostate-specific antigen (PSA) levels or a suspicious digital rectal exam, and subjected them to MRI using a 3-Tesla machine with endorectal coil. Lesions visualized on MRI were assigned a Prostate Imaging Reporting and Data System (PI-RADS) score of 1 to 5, with higher scores indicating lesions with higher degrees of clinical suspicion.

Before April 2105, when the investigators began using the PI-RADS scoring system, they used a 5-point NIH-developed scoring system that has been shown to correlate with PI-RADS scores.

Lesions were identified for biopsy by a radiologist, with a maximum of five targets identified for each patient. The patient then underwent the first biopsy with the physician guided by the MRI images superimposed over the real-time ultrasound images to identify target lesions.

Following the first biopsy the superimposed images were removed, and a second physician performed a 12-core systematic extended sextant biopsy under ultrasound guidance alone.

For patients who underwent subsequent radical prostatectomy, the investigators  looked at downgrading or upgrading of tumors by comparing the grade group determined on biopsy with that determined on postoperative whole-mount histopathological analysis.

Clinically insignificant cancer was defined as grade group 1 (Gleason score 3 + 3 = 6). Clinically significant cancer was defined as grade group 3 (Gleason score 4 + 3 = 7, unfavorable intermediate risk) or higher. The investigators also reported grade group 2 (Gleason scored 3 + 4 = 7, favorable intermediate risk) "since some physicians consider this threshold to be more clinically relevant than grade group 3 or higher."

Combined Procedure Performed Best

Of the 2103 men who underwent the tandem biopsies, 1312 received a diagnosis of cancer, and 404 of these patients with cancer underwent radical prostatectomy.

Systematic biopsy alone diagnosed cancer in 1104 patients (52.5%), and MRI-guided biopsy alone diagnosed it in 1084 patients (51.5%).

Cancer detection according to Gleason grade group, the primary endpoint, was significantly better with MRI-guided vs ultrasound-guided biopsy for diagnosis of cancer in grade groups 3 (P = .004), 4 (P < .001) and 5 (= .003), but fewer cancers in grade group 1 (P < .001).

When the MRI-targeted biopsy results were added to the systematic biopsy, 208 (9.9%) more cancers were diagnosed, and 59 of these were clinically significant (grade group 3 or greater).

Additionally, adding MRI led to an upgrading from group 1 to group 2 or higher for 134 patients with cancers that had been classified as grade group 1 on systematic biopsy, and 74 new grade group 1 cancer diagnoses among men who had no cancer detected on systematic biopsy alone.

"However, MRI-targeted biopsy alone without systematic biopsy would have led to no detection of cancers of grade group 2 or higher in 123 patients (5.8%) and no detection of cancers of grade group 3 or higher in 41 patients (1.9%)," the investigators write.

Comparing the biopsy and postsurgical pathology results, upgrading of tumors to group 3 or higher occurred in 3.5% of specimens obtained through the combined methods, compared with 8.7% of MRI-targeted-only specimens, and 16.8% of specimens obtained solely through systematic biopsy.

Ahdoot and Siddiqui have disclosed no relevant financial relationships, as do several other coauthors. Three coauthors report involvement in patents associated with prostate biopsies. The study was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, NIH Clinical Center, and NIH Center for Interventional Oncology.

N Engl J Med. Published online March 5, 2020. Abstract

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