The goal of maximizing detection of clinically significant prostate cancer (PCa) and minimizing the diagnosis of indolent disease underpins the enthusiasm with which the urologic community has embraced magnetic resonance imaging/ultrasound (MRI/US) fusion technology. Indeed, refinement of multiparametric magnetic resonance imaging (mpMRI) for PCa diagnosis and its coupling to live ultrasound imaging holds great promise for improving tissue sampling during prostate biopsy. While standard assessment parameters such as sensitivity, specificity, and positive/negative predictive value of mpMRI-assisted targeted biopsy techniques have now filled the urologic literature, practical deliverables of this technology have yet to be fully crystallized.
|FIGURE 1: A 64-year-old man with multiple previous negative standard template prostate biopsies and multiparametric MRI demonstrating a PIRADS 5 lesion in the right anterior transitional zone (left). TB of lesion demonstrated Gleason 3+4=7 disease, while 12-core template did not demonstrate evidence of cancer. A specimen from robotic nerve-sparing prostatectomy is shown (right), with the arrow indicating a notable subcapsular bulge at the site of the pathologically-proven Gleason 3+4=7 lesion (right).|
To this end, in a presentation at the American Urological Association 2016 annual meeting,1 our group sought to define metrics that could quantitate deliverables of fusion-targeted biopsy (TB). First, we defined the value added by TB techniques over traditional transrectal US-guided prostate biopsy (TRUSB). We termed this measure, the Actionable Intelligence Metric (AIM). This metric quantifies the clinically actionable data provided by TB over what was seen on TRUSB. More specifically, AIM measures the percentage of time that TB uncovered clinically actionable information that was different from that garnered through TRUSB alone. For example, the burden, procedural acumen, and expense of TB is likely justified when Gleason 8 disease is found on TB but not on TRUSB. In contrast, the increased process of care intensity inherent to TB is probably not worth the effort when both TB and TRUSB demonstrate high risk disease features. In short, this metric reports what standard test characteristic measures such as PPV and NPV are not able to describe.
The second measure we sought to describe is the TB’s ability to replace TRUSB entirely. Stated differently, how many clinically significant tumors are found on the concomitantly performed TRUSB that are not picked up by TB? In our experience, this is one of the most commonly asked questions by both patients and urologists in every day clinical practice. We termed this new instrument the Reduction Metric (ReM), which defines the percentage of patients whose biopsies were appropriately graded with TB alone.
Equations for calculated AIM and ReM are shown in Figure 2. Once the metrics were defined, we then evaluated performance of AIM and ReM for 3 clinical scenarios in which TB is most commonly employed: (1) biopsy naïve (BN) patients, (2) patients with elevated PSA and prior negative biopsy (EPNB), and (3) patients on active surveillance (AS) for “very low” and “low” risk PCa.
A prospectively collected, consecutive institutional cohort of 249 patients with documented PIRADS 3–5 lesions on prostate mpMRI were included in the study. All men underwent UroNav (Invivo; Gainesville, FL) TB with concomitant 12-core TRUSB. Patients were stratified into the 3 previously described cohorts. Clinically significant PCa was defined as Gleason Score 3+4=7 or higher. AIM and ReM were calculated for the overall cohort and for each clinical scenario (See Figure 2 for equations). The overall cancer detection rate for all patients was 61.8%. For the entire cohort, AIM and ReM were 34.1% and 81.1%, respectively. Stratified by clinical situation, the AIM was 30.8% (BN), 46.7% (EPNB), and 20.5% (AS) and the ReM was 88.9% (BN), 85.7% (EPNB), and 72.3% (AS). These percentages compared favorably to previously reported studies that offered enough published information to perform accurate calculations.
Based on the AIM calculation, TB harbors potential for improvement over traditional TRUSB techniques. Our data reveal that TB yields the most actionable information in patients with elevated PSA and prior negative biopsy (EPNB cohort AIM 46.7%) and is least helpful in AS patients (AS cohort AIM, 20.5%). Furthermore, at our institution, the ReM predicts that approximately 15% of clinically significant cancers would fail to be detected if TB was performed in the absence of concomitant TRUSB. Therefore, as shown by other investigators, TRUSB remains a necessary adjunct to TB at this time, particularly in the AS setting where up to 28% of clinically significant cancers may be missed.
In conclusion, we have introduced two new metrics—AIM and ReM—to help quantify, communicate, and compare deliverables of TB technology. It is our hope that further validation proves these metrics to be useful additions in refining the detection of clinically significant prostate cancers and minimizing overdiagnosis of indolent tumors.
The authors are affiliated with Fox Chase Cancer Center in Philadelphia.
Ristau BT, Malhotra A, Ginzburg S, et al. Defining deliverables of multiparametric magnetic resonance imaging (mpMRI)/ultrasound fusion-guided targeted prostate biopsy: Actionable intelligence metric (AIM) and reduction metric (RM). J Urol. 2016;195(4):e697.