MR/Ultrasound Biopsy Detects More High-Risk Prostate Cancers

Ricki Lewis, PhD

January 27, 2015

A targeted fusion-guided approach to prostate biopsy improves detection rates of high-risk cancers while finding fewer low-risk cancers when compared with the standard approach of 12 core biopsy that is currently used in clinical practice, according to a study published in the Journal of the American Medical Association. However, there are no clinical outcome data as yet.

The new approach electronically superimposes magnetic resonance images onto standard transrectal ultrasound images in real time, and thus provides a three-dimensional map of the prostate.

In contrast, the standard approach of taking 12 core samples seems to rely a lot on luck. "If any cancer is there, hopefully one of those 12 biopsies will catch that cancer. But you don't know. You could easily get an edge of a tumor or miss it altogether. That's been a dilemma for a long time," lead author M. Minhaj Siddiqui, MD, assistant professor of surgery at the University of Maryland School of Medicine and director of urologic robotic surgery at the Marlene and Stewart Greenebaum Cancer Center, in Baltimore, told Medscape Medical News.

Another issue is that "biopsies come into the prostate from the back and miss cancer at the front, so they aren't even that good at identifying all the cancer," commented Anthony Zietman, MD, the Jenot and William Shipley Professor of Radiation Oncology at Harvard Medical School and Massachusetts General Hospital, in Boston, Massachusetts, who was not involved in the study. He added, however, that biopsies "are good at telling us how nasty the cancer they find is," referring to the Gleason grade.

Prostate cancer is the most common cancer in men, and the 15-year survival rate for men diagnosed early is 94%. But there is much concern about overtreatment, because many men diagnosed with prostate cancer undergo surgery to treat cancers that would never have advanced.

"Because many men are overtreated, perhaps the most pressing issue in management is identification of aggressive cases. As functional and molecular imaging approaches advance, they become appealing means by which to uncover more aggressive cases," commented Martin Pomper, MD, PhD, William R. Brody Professor of Radiology at Johns Hopkins Medical School, in Baltimore. Dr Siddiqui and colleagues "hypothesized that multiparametric MR-targeted biopsy, a functional imaging approach, would prove superior at identifying high-risk prostate cancer than the conventional, random sampling approach. And that is precisely what they found in their prospective study."

Two Approaches Compared

The study began in 2007, at the National Institutes of Health, enrolling 1003 men referred for biopsy following detection of elevated prostate-specific antigen (PSA) or abnormal findings on digital rectal examination (DRE). Some of the men had had negative results on standard biopsies but were still concerned about high PSA or abnormal DRE. Participants agreed to undergo targeted and standard biopsies, performed at the same time.

Targeted biopsy detected 461 prostate cancer cases, and standard biopsy found 469. Risk categorization "demonstrated exact agreement" between the two strategies for 690 of the 1003 (69%) of the men.

Although targeted and standard biopsies detected approximately the same number of cancers, the targeted approach found 30% more high-risk cancers (173 targeted vs 122 standard, P < .001) and 17% fewer low-risk cancers (213 vs 258, P < .002). Standard biopsy cores plus targeted biopsies diagnosed an additional 103 cases (22%), of which 83% were low-risk, 12% intermediate-risk, and 5% high-risk.

It would take 200 standard biopsies combined with targeted biopsy to diagnose one additional high-risk cancer, the researchers estimated. Standard biopsy would find 17 additional cases of low- risk cancer for every additional high-risk cancer identified. Adding standard biopsy to targeted biopsy did not alter the Gleason score in 857 cases (85%), and of those whose risk category changed, 86 (9%) went from no cancer to low-risk cancer, and 19 (2%) went from no cancer or low- or intermediate-risk to higher risk.

By comparing biopsy specimens to tissue removed with prostatectomy that 170 patients underwent, the sensitivity of targeted biopsy was 77% vs 53% for standard biopsy. Specificities were similar (targeted, 68%, vs standard, 66%).

The fused approach might calm fears in some patients, Dr Siddiqui said. "We found that the low-risk, low-volume cancer that's not aggressive doesn't show up on MRI. Targeted biopsy doesn't even catch those; it decreases the rate of diagnoses of low-risk prostate cancers by 17%. And that's helpful. Most of these people would live their whole lives and die of other causes. But they go into a doctor's office and are diagnosed with prostate cancer and go through the mental anguish of thinking, 'I have cancer in my body now,' " Dr Siddiqui said.

The new approach will influence active surveillance, according to Dr Siddiqui. "A provider can feel more confident telling someone with a low-risk diagnosis based on targeted biopsy that the chances are there's not something hiding in the prostate you're missing. Now we are no longer relying on 12 random pieces."

Dr Pomper, who was not involved in the research, commented to Medscape Medical News: "This study is an important step toward identifying patients who would be more likely to benefit from definitive therapy and shows that MR guidance alone provides the best decision guide with respect to performing surgery. As duly noted by the authors, that this result portends lower morbidity or mortality remains to be seen, but it certainly makes sense that ferreting out the most aggressive cases ― and treating them appropriately ― will do just that."

Limitations of the study include the mix of situations that prompted men to participate and the fact that the study did not assess clinical endpoints such as recurrence and mortality. Patients with no visible lesions on MRI were excluded, which may explain the lower detection of low-risk cancers.

In an accompanying editorial, Lawrence H. Schwartz, MD, from the Department of Radiology, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, in New York City, and Ethan Basch, MD, from the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, applaud targeted fusion biopsy. "Any test that can inform decision making and potentially spare patients harm is immediately appealing, even if the effect on clinical outcomes is unknown," they write. However, they caution against wide adoption until further investigations demonstrate clear "benefits on quality of life, life expectancy, or, ideally, both."

The role of MRI in prostate biopsy is evolving. "We're still trying to work out how and where to incorporate MRI. MRI has improved so much in recent years that it stands a chance of replacing biopsies in some cases," commented Dr Zietman.

Study coauthors Dr Choyke and Dr Pinto hold a patent related to the MR/ultrasound fusion biopsy platform, and Dr Wood holds several patents related to imaging and prostate biopsy. Commentator Dr Schwartz received an honorarium from Pfizer and has consulted for Celgene, Novartis, Icon, and BioImaging. The other authors and commentators have reported no relevant financial relationships.

JAMA. 2015;313:390-397. Full text, Editorial


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