An elegant study by Siddiqui et al1—reviewed in this issue of The ASCO Post—offers compelling evidence for the diagnostic utility of “targeted” prostate biopsy using multiparametric magnetic resonance imaging (MRI) data fused with ultrasound images. The technique involves first performing a dedicated prostate MRI examination in which several pieces of complementary anatomic and functional data are acquired in a single combined scan. During a separate biopsy procedure performed at a different time and location, the MRI data are then fused with real-time ultrasound to provide guidance for biopsy passes targeted at suspicious foci within the gland.
In their prospective study of 1,003 men referred for elevated prostate-specific antigen levels or abnormal digital rectal examinations, the authors found that targeted biopsy yielded 30% more high-risk cancers and 17% fewer low-risk cancers compared to standard extended-sextant biopsy. Given the evolving understanding that low-risk prostate cancers may be amenable to observational strategies rather than immediate surgery or radiation,2 this technology offers the enticing prospect of more effectively triaging prostate cancer patients to appropriate therapeutic pathways.
Technique and Equipment
The study gives rise to a number of unanswered questions and avenues for further investigation. First, the technique for acquiring, interpreting, and fusing multiparametric MRI of the prostate is far from standardized, and further work is required to understand how diagnostic performance changes with different methods. In this study, MRI was performed on a 3.0 Tesla Philips scanner using an endorectal coil, but all major magnetic resonance hardware vendors offer prostate imaging packages with slight variations between the systems, and clinical MRI is currently performed at different field strengths and either with or without an endorectal coil.
The authors interpreted the multiparametric MRI scans using a qualitative scale of their own design,3 but approaches for interpreting and reporting multiparametric MRI of the prostate are still rapidly evolving. The European Prostate Imaging and Reporting and Data System (PI-RADS) classification system,4 which had not yet been released when the current study was launched, has already spawned a PI-RADS version 2 revision describing a slightly different methodology,5 and many authors continue to investigate alternative reporting schemes that may have higher inter-reader reproducibility.6 This study incorporated functional MRI information from dynamic contrast-enhanced MRI, diffusion-weighted MRI, and magnetic resonance spectroscopic imaging, but the latter is a technique performed more commonly in Europe than in the United States and was in fact omitted from PI-RADS version 2.
This study used an electromagnetic tracking system (UroNav, Philips-Invivo) for co-registering or “fusing” the MRI data to the ultrasound images, but other technologies are available, including robotic tracking via a mechanical arm with built-in encoders (Artemis, Eigen; BioJet, Geoscan) and tracking with a three-dimensional ultrasound probe (Urostation, Koelis). It should be noted that all of these technologies appear to improve over “in-bore” magnetic resonance–guided biopsy, which is expensive, time-consuming, requires MRI-compatible equipment, and cannot be performed as an in-office urology clinic procedure.
Decision Analysis
Second, further work is required to understand how this technology should be integrated into diagnostic and therapeutic algorithms. The authors present a decision analysis suggesting that targeted biopsy may be superior to both standard biopsy and combined (targeted plus standard) biopsy strategies at intermediate threshold probabilities (ie, when an individual patient is not so desirous of treatment that the optimal strategy would be “always treat” and not so averse to treatment that the optimal strategy would be “never treat”).
The decision analysis model apparently used data from 170 patients who underwent radical prostatectomy and therefore had whole-gland pathology specimens available for comparison to the biopsy results. In this subset of patients, targeted biopsy had intermediate sensitivity (77%) for intermediate- or high-risk prostate cancer compared to standard biopsy (53%) or combined biopsy (85%) but had higher specificity (68% compared to 66% and 49%) and a higher area under the receiver operating characteristic curve (AUC = 0.73 vs 0.59 and 0.67).
However, it is unclear from the paper whether the dominance of the targeted biopsy strategy holds true for patients with no prior biopsy, in whom standard biopsy appears to have a higher sensitivity for high-risk prostate cancers. For patients with no prior biopsy, future studies may help us understand whether targeted biopsy should be deployed alone, in combination with standard biopsy, or only if standard biopsy yields a negative result.
Also, this study was confined to patients who had at least one lesion detected on multiparametric MRI. Recent retrospective studies have yielded somewhat conflicting data on the ability of mp-MRI to detect high-risk prostate cancer.7,8 Large prospective trials are required to determine whether a negative multiparametric MRI alone may be enough to warrant forgoing biopsy altogether and triaging patients to an active surveillance strategy.
Costs and Outcomes
Finally, a comprehensive assessment of this emerging technology will require evaluation of its effects on costs and long-term patient outcomes. Widespread adoption of MRI/ultrasound fusion–guided biopsy would be expensive but may turn out to be cost-effective from a societal perspective after accounting for reductions in overdiagnosis and overtreatment.9
Moreover, as noted in a JAMA editorial by Schwartz and Basch,10 it remains to be proven that use of targeted biopsy will translate into an improvement in clinically meaningful long-term outcomes, including symptoms, functional status, and survival. We eagerly await further results, ideally from randomized controlled clinical trials, to guide the dissemination and utilization of this promising technology. ■
Disclosure: Drs. Abramson and Arora reported no potential conflicts of interest.
References
1. 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. JAMA 313:390-397, 2015.
2. Ganz PA, Barry JM, Burke W, et al: National Institutes of Health State-of-the-Science Conference: Role of active surveillance in the management of men with localized prostate cancer. Ann Intern Med 156:591-595, 2012.
3. Yerram NK, Volkin D, Turkbey B, et al: Low suspicion lesions on multiparametric magnetic resonance imaging predict for the absence of high-risk prostate cancer. BJU Int 110:E783-E788, 2012.
4. Barentsz JO, Richenberg J, Clements R, et al: ESUR prostate MR guidelines 2012. Eur Radiol 22:746-757, 2012.
5. American College of Radiology: Prostate Imaging and Reporting and Data System: Version 2 (PI-RADS v2). Available at http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2.pdf. Accessed July 16, 2015.
6. Rosenkrantz AB, Lim RP, Haghighi M, et al: Comparison of interreader reproducibility of the prostate imaging reporting and data system and Likert scales for evaluation of multiparametric prostate MRI. AJR Am J Roentgenol 201:W612-W618, 2013.
7. Meng X, Rosenkrantz AB, Mendhiratta N, et al: Relationship between prebiopsy multiparametric magnetic resonance imaging (MRI), biopsy indication, and MRI-ultrasound fusion-targeted prostate biopsy outcomes. Eur Urol. June 22, 2015 (early release online).
8. Tan N, Margolis DJ, Lu DY, et al: Characteristics of detected and missed prostate cancer foci on 3-T multiparametric MRI using an endorectal coil correlated with whole-mount thin-section histopathology. AJR Am J Roentgenol 205:W87-92, 2015.
9. de Rooij M, Crienen S, Witjes JA, et al: Cost-effectiveness of magnetic resonance (MR) imaging and MR-guided targeted biopsy versus systematic transrectal ultrasound-guided biopsy in diagnosing prostate cancer: A modelling study from a health care perspective. Eur Urol 66:430-436, 2014.
10. Schwartz LH, Basch E: MR/ultrasound fusion-guided biopsy in prostate cancer: What is the evidentiary standard? JAMA 313:367-368, 2015.
Dr. Abramson is Assistant Professor of Radiology and Radiological Sciences, and Dr. Arora is Instructor in Clinical Radiology and Radiological Sciences at Vanderbilt University Medical Center, Nashville.
