Clinical utility of the exosome based ExoDx Prostate(IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL

Abstract

Background: The ExoDx Prostate(IntelliScore) (EPI) test is a non-invasive risk assessment tool for detection of high-grade prostate cancer (HGPC) that informs whether to proceed with prostate biopsy. We sought to assess the impact of EPI on the decision to biopsy in a real-world clinical setting.

Methods: We conducted a prospective, randomized, blinded, two-armed clinical utility study that enrolled 1094 patients with 72 urologists from 24 urology practices. Patients were considered for prostate biopsy at enrollment based on standard clinical criteria. All patients had an EPI test; however, patients were randomized into EPI vs. control arms where only the EPI arm received results for their biopsy decision.

Results: In the EPI arm (N = 458), 93 patients received negative EPI scores of which 63% were recommended to defer biopsy by the urologist and 74% ultimately deferred. In contrast, 87% of patients with positive EPI scores were recommended to undergo biopsy with a 72% compliance rate to the urologist's recommendation. This led to detection of 30% more HGPC compared to the control arm, and we estimate that 49% fewer HGPC were missed due to deferrals compared to standard of care (SOC). Overall, 68% of urologists reported that the EPI test influenced their biopsy decision. The primary reason not to comply with EPI results was rising PSA.

Conclusion: To our knowledge this is the first report on a PC biomarker utility study with a blinded control arm. The study demonstrates that the EPI test influences the overall decision to defer or proceed with a biopsy and improves patient stratification.

Fig. 1. Study flow diagram of the blinded, two-armed clinical utility study of the ExoDx Prostate EPI test.

Patients were considered for a prostate biopsy at enrolment based on standard clinical criteria. All subjects had an EPI test; however, patients were randomized into an EPI and control arm where only the EPI arm received the results. Neither subjects nor urologists were notified in advance whether they were going to receive the EPI test result for their clinical assessment. For EPI arm subjects the treating urologist received the test results for review with the patient during the final evaluation prior to biopsy. For control arm subjects, the urologist received a notification of No EPI Result and continued biopsy discussion per standard of care.

Fig. 2. Consort flow diagram.

Seventy-two urologists from 24 clinical sites enrolled 1094 subjects to the study. Subjects were excluded if they were outside of the inclusion criteria, failed assay controls or were missing the post-EPI questionnaire, leaving 942 patients for EPI and Control arms.

Fig. 3. Decision tree and outcome for the EPI arm.

Of the 458 subjects that received the EPI test results, 93 were low risk (<15.6) for which 63% were recommended to defer their biopsy with a 92% compliance. The remaining 37% of the EPI low risk subjects were recommended to have a biopsy; however, 44% ultimately decided to defer biopsy. Overall, 69 subjects, representing 74% of all EPI low risk subjects ended up deferring biopsy.

Fig. 4. Biopsy decision as a function of EPI risk score.

The biopsy decision rate is plotted as a function of the EPI score and superimposed on the light blue area representing risk of HGPC from previous EPI-biopsy outcome validation studies (9,13). Only 26% of EPI low risk (<15.6) subjects proceeded with a biopsy compared to 39% (95% CI: 35–44%) in the control arm (vertical yellow line). As illustrated, urologists used the <15.6 cut-off as a rationale to support biopsy deferral and a >20 EPI score for proceeding with a biopsy due to the increased risk of finding HGPC. An EPI score over 30 indicates an increased risk of finding HGPC relative to patients normally biopsied based on SOC factors (the prevalence of HGPC was 31.6% in the control arm).