MR/Ultrasound Fusion–Guided Biopsy in Prostate Cancer
Authors: Lawrence H. Schwartz, Ethan Basch
Journal: JAMA (2015)

Although the benefits of prostate cancer screening have come into question recently,1 for men who are screened and have elevated prostate-specific antigen (PSA) levels, or those who present with symptoms, prostate biopsy remains the next step in the diagnostic workup. The objective of biopsy is first to determine whether any cancer is present and then to determine tumor grade (ie, Gleason score) because it predicts clinical outcomes. Lower-grade localized tumors are generally felt to be amenable to active surveillance, whereas higher-grade tumors are more commonly recommended for a definitive intervention.2 Moreover, for men undergoing definitive radiation therapy, the grade of the tumor is a key determinant in whether concomitant androgen deprivation therapy is recommended.3 However, biopsies underestimate tumor grade compared with subsequent prostatectomy up to 40% of the time.4 Therefore, any new technology that improves the ability of biopsy to distinguish between men with lowerand higherrisk cancers has the potential to influence clinical decisions and improve patient outcomes. Magnetic resonance imaging (MRI) of the prostate was initially introduced in the 1980s, with substantial technical advances since that time and increasing use for staging and treatment planning amongmenwho already have a diagnosis of prostate cancer.5-8 Current techniques combine visual qualitative assessment of the prostate gland and surrounding tissues as well as a quantitative assessment. Detection and characterization of prostate cancer using MRI can involve several different MRI pulse sequences that provide complementary information about the gland and potential for cancer within the gland. Known as “multiparametric” imaging,9 these sequences include anatomic localization of the normal gland and cancer, MRI spectroscopy for evaluation of metabolites including choline and citrate, perfusion MRI with contrast for angiogenesis, and diffusion MRI measuring magnitude of molecular movement in normal prostate and in cancer with increased cellularity and altered glandular structure of prostate gland. There is nascent interest in theuseof prostateMRI to riskstratifymen for active surveillance programs,with initial evidence thatpatientswithvisible lesionsonMRImoreoftenhave adverse pathology on subsequent biopsy compared with patientswithnonvisible lesions.10 Similarly, interest anduse are increasing to extend the use ofMRI to guide the biopsy in initial diagnostic evaluation, based on findings that localization ofhigh-gradeor clinically significant tumors is improved.11 For example, in a prior study among undiagnosed men presenting with symptoms suggestive of prostate cancer, MRIguided biopsy was reported to improve detection of prostate cancer comparedwith sextant (nonguided)biopsy.12 It hasalso beensuggested thatusingMRI rather thanultrasound toguide biopsies is cost-effective based on assumptions about reductions in overtreatment.13 The ability to fuse imaging modalities such as ultrasound with MRI is an exciting innovation with the potential to enhance the diagnostic capabilities of unguided or single-modality image-guided biopsy, as reflected in the study by Siddiqui and colleagues14 in this issue of JAMA. This approach improves spatial localization and capture of location in 3 planes.15 In a prior analysis by this group among 315 men diagnosed with prostate cancer, the use of MR/ultrasound fusion–guided biopsy led to upgrading of Gleason grade in 32% of patients compared with sextant (nonguided) biopsy alone.16 The current report, a prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007-2014 at the National Cancer Institute, builds on these previous findings. In this study, targeted MR/ultrasound fusion biopsy diagnosed 461 cases of prostate cancer and standard biopsy diagnosed 469 cases. There was diagnostic agreement between targeted and standard biopsy in 690 men who underwent biopsy (69%), although targeted biopsy diagnosed 30% more high-grade cancers compared with standard biopsy (173 vs 122 cases) and 17% fewer lower-grade cancers (213 vs 258 cases). Notably, there was no discernable difference in the number of cancers detected, only in the grade of identified cancers. Given the role of tumor grade in pretreatment risk stratification and decision making, improvement of the accuracy of high-grade tumor detection by biopsy is desirable, and the results of this study are compelling for patients and clinicians. Nonetheless, it remains unknown if use of this technique and shifts in cancer grade among patientswhounderwent biopsy will translate into clinically meaningful outcomes such as benefits in symptoms, functional status, or survival. The promise of this technique is that improved tumor grade classificationwill enablemore appropriate treatment recommendations—eg, higher-intensity treatment for menwith higherrisk disease and active surveillance for men with low-grade tumor. It is notable that the studies thatdeterminedwhichpatients are best suited to more or less intense treatment and which men should be classified as high risk did not use MRIRelated article page 390 Opinion