European Urology

Since the introduction of prostate-specific antigen (PSA) screening, the lifetime risk of being diagnosed with prostate cancer (PCa) has doubled, from 8% to 17% [1]. The sharp rise in the incidence of PCa has been accompanied by a reduction in PCa-specific mortality [2]. Although advances in treatment may explain the dramatic change in the epidemiology of PCa, the diagnosis of low-risk cancer in asymptomatic men may largely contribute to the reduction in disease mortality. It is clear that the greatest risk of screening is overdetection of indolent disease, and the greatest risk of overdetection is the consequences of unnecessary treatment. These disturbing trends in the management of localized PCa have refocused efforts in research to personalize management by improving risk stratification and enabling effective treatment allocation in which active surveillance, focal therapy, and radical surgery or radiotherapy lie on a continuum of complementary therapies. Therefore, advancements in technology driven to improve PCa detection, such as image-guided prostate biopsy on a magnetic resonance platform, are met with considerable resistance and are subsequently criticized for contributing to the overdetection of PCa. However, proponents may argue that targeted biopsies will reduce the detection of insignificant cancer and mitigate the complications associated with extended biopsy templates.

Before discussing the implications of magnetic resonance imaging (MRI)–targeted biopsy for the contemporaneous management of PCa, it is important to return to the original report that defined the role of random sextant sampling of the prostate. In their landmark study, Hodge et al. still emphasized the importance of accompanying targeted biopsies with the sextant biopsy: “When combined with additional directed biopsies of the rare hypoechoic areas not included in the pattern of systematic sampling, it provides a highly accurate means to diagnose PCa, minimizing observer and sampling errors.” Importantly, the study cohort included men with palpable tumors and more advanced disease compared with the current era of asymptomatic PSA-detected PCa. Therefore, the rising prevalence of PCa and dramatic stage migration have ushered in new interest in old concepts and a return to targeting biopsies only to areas of clinically significant cancer.

In this timely and well-done systematic review, Moore et al. [3] characterize the effectiveness of MRI-targeted prostate biopsy in the diagnosis of PCa. In their synthesis of the available evidence, the authors attempt to answer whether MRI-targeted prostate biopsies are more selective in detecting clinically significant PCa in men with risk of PCa identified by elevated serum PSA or digitally palpable tumor on rectal examination. Despite the central relevance of this question for evaluating the value of MRI-targeted biopsy, few studies were designed to effectively provide data and support these ideas. In fact, the paucity of quality prospective studies sufficiently powered to demonstrate the accuracy of MRI-targeted biopsy compared with standard transrectal ultrasound (TRUS)–guided prostate biopsy is disappointing and highlights the urgent need for scientific exploration to lead advancements in technology instead of the opposite direction.

The heterogeneity in patient cohorts, interventions, and outcomes is the major limitation of studies in MRI-guided prostate biopsy. The prevalence of PCa varies based on the risk of the men selected and directly affects the positive and negative predictive value, thereby restricting comparisons across study populations. In addition, men should be randomized to receive MRI-targeted biopsy with standard TRUS-guided biopsy or only standard TRUS-guided biopsy conducted independently of MRI data to mitigate biases with physician cognitive targeting. Finally, the radiologic interobserver variability across studies needs to be minimized by standardizing image quality, implementing multiparametric assessment, and defining thresholds to declare a lesion as present.

In their review, Moore et al. [3] measure clinically significant cancer detection as the primary outcome. Most studies defined PCa detection as a binary variable, which is counterproductive in efforts to reduce overdiagnosis of indolent disease. Recent studies have focused on determining the highest Gleason grade on biopsy and correlation with final pathology in the radical prostatectomy specimen [4] and [5]. In addition, investigators have demonstrated that lesions identified on MRI correlate with histopathologic specimens using patient-specific MRI-based prostate molds [6].

The authors astutely discuss the implications of comparing standard and targeted approaches on a per-core basis to allow assessment of the efficiency of a targeted approach. In addition, reporting detection of tumors on a per-core basis is relevant for strategies to allay discomfort and reduce complications. The authors report the frequency of cancer detection among patients with MRI-detected lesions; however, the denominator should include patients without a tumor identified on MRI.

The management of men with early-stage PCa has become an important public health issue. As more studies of MRI-targeted prostate biopsy mature, investigators should concurrently collect data estimating costs associated with these advanced techniques—specifically, measuring the total procedure time, costs of incremental cores, complications, and barriers in processes in care, including MRI availability. The assessment of costs should include sophisticated metrics to evaluate the economic benefits of lowering the overdiagnosis of indolent disease and eliminating repeat biopsy strategies to confirm accurate staging.

Men with localized PCa face difficult decisions regarding the management of their disease because of limitations with risk stratification and the paucity of randomized trials comparing various treatments. Real problems in systematic errors with routine TRUS-guided biopsy need to be improved, and the infectious and bleeding complications associated with expanded biopsy strategies represent an imperfect solution [7]. The use of imaging for targeting biopsies would bring PCa diagnosis into line with the biopsy technique used for the detection of almost all other solid tumors and improve the detection of significant cancers and the prediction of insignificant disease [8]. It appears that as we move into the future, some answers may be found in lessons from the past.

Conflicts of interest

The authors have nothing to disclose.