Introduction:

We aimed to assess the performance of IsoPSA in a clinically relevant target population comprised of cohorts without pre-biopsy mpMRI and with pre-biopsy mpMRI PI-RADS scores 1-3 in a large- scale prospective clinical validation study.

Methods:

566 patients with age ≥ 50 years & total PSA ≥ 4 - 10 ng/mL comprised the evaluable study population undergoing prostate cancer (PCa) early detection. All patients received prostate biopsy and IsoPSA. Patients and investigators were blinded to all IsoPSA results. Subjects with mpMRI PI-RADS 4-5 scores excluded due to high PCa risk leading to a biopsy decision according to standard of care. IsoPSA performance overall and in subgroups of patients 1) without pre-biopsy mpMRI & 2) with pre-biopsy mpMRI PI-RADS 1-3 were assessed in relation to a high-grade PCa (Grade Group ≥ 2) biopsy outcome by: Likelihood ratio analysis of pre-test risk (prevalence) & post-test risk at an IsoPSA Index lower cutoff = 6.0 & an IsoPSA Index upper cutoff =10.0 to define test negative & positive predictive characteristics.

Results:

Of 566 patients comprising the study population, 362 (64%) had no pre-biopsy mpMRI and 204 (36%) had pre-biopsy mpMRI PI-RADS 1-3 scores. Overall and in both subgroup cohorts, IsoPSA displayed statistically informative negative and positive predictive characteristics by LR analysis (95% CIs) as shown in Tables: 1, 2, and figure 3. 

1)  post-test risk point estimates at the lower IsoPSA Index cutoff of ≤ 6.0 and at the upper IsoPSA Index cutoff of > 10.0 are substantially below and above the pre-test risk (prevalence), and the pre- test risk falls outside of the 95% CI for post-test risk at both lower and upper IsoPSA Index cutoffs - overall and for both subgroups.

2)   post-test risk point estimates at the lower and upper cutoffs, respectively, indicate significantly low false negative rates and clinically informative true positive rates in the overall, No mpMRI, and mpMRI PI-RADS 1-3 datasets in comparison to disease prevalence.

Figure 1 highlights the clinical use and positioning of IsoPSA in a contemporary early detection paradigm based on baseline risk alone and baseline risk + mpMRI.

Conclusion:

IsoPSA is now directly validated both without and in combination with mpMRI PI- RADS 1-3 scores. Consequently, use of IsoPSA in clinical practice should produce demonstrable improvements in clinician-patient shared biopsy decision-making.

Funding: Cleveland Diagnostic Inc.