Targeted prostate biopsy: Momentum grows, but questions remain

Use of targeted magnetic resonance (MR)/ultrasound fusion biopsy (“targeted biopsy”) resulted in the diagnosis of significantly more high-risk prostate cancers and significantly fewer low-risk cancers compared with a standardized systematic biopsy technique, reported the authors of a new study from the National Cancer Institute (NCI).

The findings were published in JAMA (2015; 313:390-7).

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Given the strengths of the study, which include the size and prospective enrollment of its population (1,003 men), the research lends significant support to the idea that targeted biopsy is a promising technique for minimizing the problems of prostate cancer overdetection and overtreatment, according to lead author M. Minhaj Siddiqui, MD, and Samir Taneja, MD, a proponent of targeted biopsy.

However, speaking to Urology Times, both urologists pointed out that the potential impact of the study must be considered in light of its limitations. As a bottom line, more work needs to be done to determine the role of targeted biopsy in prostate cancer detection.

Dr. SiddiquiDr. Siddiqui, assistant professor of surgery-urology at the University of Maryland School of Medicine, Baltimore, was involved in the study as a urologic oncology fellow at the NCI.

“The findings of our study are consistent with the idea that findings on multiparametric prostate MRI better reflect the real disease in the prostate and therefore guide a biopsy that provides better risk stratification,” he said. “However, our study was not randomized; it looked at pathology results rather than clinical outcomes; and most of the men had undergone prior standard biopsy, often with negative results.

“Ideally, prospective, randomized trials should be conducted to establish that targeted biopsy reduces risk of disease recurrence or prostate cancer-specific mortality, and we look to leading centers implementing this technique to design clinical trials that will give us the type of information needed to advance the field.”

Next: Not ready for clinical practice

Not ready for clinical practice

Dr. Taneja“This is an important paper strengthening the idea that targeted biopsy has a role in prostate cancer detection for allowing more accurate assessment of disease and better detection of high-risk cancer,” said Dr. Taneja, professor of urology and radiology at the NYU Langone Medical Center, New York. “However, we cannot use this study to define how urologists might use targeted biopsy in clinical practice.”

The study analyzed data from men referred to the NCI between 2007 and 2014 with elevated PSA or an abnormal digital rectal examination. Eighty percent of the men had a prior biopsy, of which about 54% were negative. All of the men were found to have areas of prostate cancer suspicion on multiparametric prostate MRI and then underwent concurrent targeted biopsy (mean cores per patient, 5.3) and extended-sextant biopsy (“standard biopsy”; mean cores per patient, 12.3). None of the men had received any treatment for prostate cancer, but 170 went on to prostatectomy.

The targeted and standard biopsy techniques identified cancer in nearly the same number of men: 461 and 469 cases, respectively. However, the targeted biopsy performed significantly better than the standard technique or even the combination of the two in detecting high-risk disease.

Compared with the standard biopsy, targeted biopsy diagnosed 30% more high-risk cancers (p<.001) and 17% fewer low-risk cancers (p=.002). In addition, although 22% more cases of prostate cancer were identified using both techniques versus targeted biopsy alone, 83% of the additional cancers were low risk and only 5% were high risk.

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Based on those data, it was determined that 200 men would need to have the combined biopsy in order to diagnose one additional high-risk cancer, but at the same time, 17 additional low-risk cancers would be found.

Other analyses focusing on the 170 men who underwent prostatectomy also favored targeted biopsy. Compared with both standard biopsy and the combination of the two techniques, the findings from the targeted biopsy better reflected the pathology in the whole prostate gland. Using the technique of decision curve analysis, the investigators found the targeted biopsy was superior to the standard technique or combination approach for guiding the recommendation for surgery.

“It turned out that when combining the two techniques, the standard biopsy led to enough bad decisions that it undermined the value of the targeted biopsy,” Dr. Siddiqui said.

Next: Prior biopsy an 'important limitation'

Prior biopsy an ‘important limitation’

Dr. Siddiqui and co-authors acknowledged that the predominance of men with a prior biopsy in the study population is an important limitation. Considering the potential for bias, subcohort analyses were undertaken in men with and without prior biopsy, and the results showed risk distribution for the targeted biopsy was similar in the two groups.

“The findings are reassuring that targeted biopsy has a benefit in biopsy-naïve men, but they are just subgroup analyses, and it will be important to see if the outcomes are validated as other centers investigate biopsy-naïve populations,” Dr. Siddiqui said.

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Commenting on the population characteristics, Dr. Taneja explained that the performance of targeted biopsy differs depending on the indication.

“Among biopsy-naïve men, systematic biopsy tends to identify a lot of low-grade, low-risk cancers that are small in volume, whereas the targeted approach tends to avoid detection of those lesions and maintain or increase the detection of high-grade disease. However, among men who had a previous standard biopsy with a negative result, both the systematic and targeted biopsy do not find much low-risk cancer due to a lower prevalence of disease, but the targeted biopsy tends to find more high-grade disease,” he explained.

“Due to the different underlying prevalence of disease in men with and without prior biopsy, it really cannot be concluded based on findings from the whole NCI study cohort whether targeted biopsy reduced prostate cancer overdetection.”

High-grade misses: A red flag?

Dr. Taneja also observed that the number of high-grade cancers missed by the targeted biopsy may raise a red flag for urologists, considering that appears to be a common community concern about targeted biopsy. Illustrating his point, Dr. Taneja noted that results of an audience poll at the Society of Urologic Oncology 2014 winter meeting in Bethesda, MD showed that 99% of attendees who listened to a debate about targeted biopsy said they would not use multiparametric MRI to guide the procedure. Their main reason was that it misses high-grade disease.

He suggested that targeting error might account for the high-grade cancers missed by the targeted biopsy in the NCI study and in the majority of studies published to date, noting that in the NYU series, which will be presented at the 2015 AUA annual meeting in New Orleans, the rate of missed high-grade cancer is lower, perhaps due to improved targeting techniques with the evolution of co-registration devices.

READ: MRI may add value in monitoring men on surveillance

“The NCI cohort was studied over a 7-year period beginning in 2007, and certainly the imaging, its interpretation, and methods for biopsy have evolved and are improved,” Dr. Taneja said. “The reality is that systematic biopsy misses more high-grade disease than the targeted approach.”

Next: Technology, learning curves remain

Technology, learning curve hurdles remain

Dr. Taneja’s remarks are a reminder of certain pragmatic issues affecting the dissemination of targeted biopsy. Dr. Siddiqui pointed out that the 3T technology used for multiparametric prostate MRI is currently not widely available, and even at centers where it is installed, there may not be a radiologist with the necessary expertise to interpret the scan.

“In our study, all of the scans were read by two highly experienced genitourinary radiologists. However, there is a learning curve to reading the prostate multiparametric MRI, and it is easy for radiologists who are new to the interpretation to overcall suspicious areas,” Dr. Siddiqui said.

READ: MRI-targeted prostate biopsy offers four fundamental benefits

Dr. Taneja added that experience with the technique of targeted biopsy is another hurdle that must be cleared by urologists prior to implementation of MR-targeted biopsy in the community.

“While commercially available co-registration platforms may help in reducing the learning curve, we have learned from community feedback that there is great variability in the ease of use for such platforms, and the learning curve with certain devices may be considerable,” Dr. Taneja said.

Based on their belief that multiparametric MRI provides more reliable imaging of the prostate, Dr. Siddiqui and colleagues at the University of Maryland are initiating studies investigating its use with targeted fusion biopsy in men undergoing active surveillance and to guide focal brachytherapy in appropriate candidates.

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