Prostate tumors are most commonly diagnosed via transrectal ultrasound (TRUS)-guided biopsy, usually in response to an elevated prostate-specific antigen (PSA) test.

These biopsies are performed in a templated fashion in which 10 to 12 cores are taken from areas of the prostate where tumors most commonly reside. Although this conventional approach has resulted in many appropriate diagnoses of prostate cancer, its dependence upon a non-image—guided sampling method is unique among solid malignancies. These techniques, in place for decades, exhibit room for improvement and the focus is shifting toward using more sophisticated imaging methods not just for staging but also for detection.

The traditional biopsy method presents 3 areas of concern. First, there is a considerable risk of a “false-negative” biopsy—in more than 20% of cases by some reports

—where significant cancer resides in a region of the prostate not sampled by a template-based biopsy.

Second, if diagnosed with low-risk cancer, more than one-third of patients treated with radical prostatectomy demonstrate more aggressive disease not detected by template-based biopsy.

 Third, only about one-quarter of biopsies give rise to cancer diagnoses, suggesting that PSA testing alone for screening results in many unnecessary biopsies.

To address limitations of traditional prostate biopsy methods, many have looked to multiparametric magnetic resonance imaging (mpMRI) of the prostate as a mechanism to improve cancer detection among men at risk for prostate cancer.

Prostate MRI with T1/T2 weighted imaging has been utilized since the 1980s, but primarily played a role in clinical staging rather than cancer detection. Over time, novel techniques harnessing contrast-enhanced and diffusion-weighted images, as well as magnetic resonance (MR) spectroscopy, were incorporated and utilized to attempt to improve cancer detection with imaging alone.

In 2014, the International Prostate MRI Working Group released the Prostate Imaging Reporting and Data System (PI-RADS v2) which serves as the international standard for performing and reporting prostate mpMRI.

In parallel with these advances in prostate mpMRI, select centers were evaluating methods to utilize mpMRI to help guide prostate biopsies.

A magnetic resonance-ultrasound (MR-US) fusion biopsy uses software to co-register mpMRI results with real-time TRUS images so that urologists can perform MR-guided biopsies in the clinic. Initial investigation for this approach demonstrated improved detection of clinically significant cancer among patients with multiple previous negative biopsies compared with traditional TRUS-guided biopsies.

From there, other work demonstrated improved cancer detection among patients who were biopsy naïve

 and showed the ability to track specific tumors among patients with prior cancer diagnoses being managed with active surveillance.

These initial studies represented preliminary work that led to 2 publications in 2015 and 2016 that summarized results from early adopters of this MR-US fusion approach for prostate biopsy.

At the National Cancer Institute, Mohummad Siddiqui, MD, and colleagues reported their experience using the UroNav MR-US fusion biopsy device among a diverse group of 1003 patients undergoing a workup for prostate cancer.

They reported that an approach relying on targeted biopsies alone detected 30% more highrisk tumors and 17% fewer low-risk tumors than a standard TRUS-guided systematic approach.

Furthermore, based on their data, they concluded that combining targeted biopsies with systematic sampling did not result in greater predictive ability than targeted biopsies alone.

On the other hand, a group led by Leonard S. Marks, MD, at the University of California, Los Angeles published their experience using the Artemis MR-US fusion biopsy device among 1042 men. They found that combining targeted and systematic biopsies resulted in more clinically significant prostate cancer diagnoses than either approach alone.

In both studies, no matter what the approach, the MR-US fusion biopsy was able to identify considerably more clinically significant cancer and more frequently avoid diagnoses of indolent tumors compared with the traditional templatebased prostate biopsy.

Despite the benefits of this novel tactic to detect prostate cancer, questions and concerns remain. Execution of mpMRI requires significant capital and expertise, and the effectiveness of these methods among new adopters is not known. Furthermore, any slight risk of a false-negative diagnosis based on imaging alone makes it difficult to recommend against tissue sampling in the setting of “normal” mpMRI findings.

However, recent results from the PROMIS trial, presented at the 2016 ASCO Annual Meeting, demonstrated that upfront mpMRI for biopsy-naïve patients may avoid an unnecessary biopsy for onequarter of men with an abnormal PSA.

Continuing research will have to evaluate whether combining serum biomarkers or other measurable clinical factors with mpMRI results can help make negative or inaccurate prostate biopsies a rarity rather than the norm.

Djavan B, Ravery V, Zlotta A, et al. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3, and 4: when should we stop? 

Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. 

Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Barentsz JO, Weinreb JC, Verma S, et al. Synopsis of the PI-RADS v2 guidelines for multiparametric prostate magnetic resonance imaging and recommendations for use. 

Vourganti S, Rastinehad A, Yerram NK, et al. Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal biopsies. 

Sonn GA, Chang E, Natarajan S, et al. Value of targeted prostate biopsy using magnetic resonance-ultrasound in men with prior negative biopsy and elevated prostate-specific antigen. 

Abd-Alazeez M, Kirkham A, Ahmed HU, et al. Performance of multiparametric MRI in men at risk of prostate cancer before the first biopsy: a paired validating cohort study using template prostate mapping biopsies as the reference standard. 

Sonn GA, Filson CP, Chang E, et al. Initial experience with electronic tracking of specific tumor sites in men undergoing active surveillance of prostate cancer.

Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. 

Filson CP, Natarajan S, DJA Margolis, et al. Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: the role of systematic and targeted biopsies. 

Ahmed HU, Bosaily AE, Brown LC, et al. The PROMIS study: a paired-cohort, blinded confirmatory study evaluating the accuracy of multi-parametric MRI and TRUS biopsy in men with an elevated PSA.

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Continuing research will have to evaluate whether combining serum biomarkers or other measurable clinical factors with multiparametric magnetic resonance imaging results can help make negative or inaccurate prostate biopsies a rarity rather than the norm.

Christopher P. Filson, MD, MS

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