# Clinical Utility of PROSTest: A Prospective Study Suggesting Reduction in Unnecessary MRI and Biopsy in Men Evaluated for Prostate Cancer

## TL;DR

PROSTest is a blood test that accurately identifies men at risk for significant prostate cancer, potentially reducing the need for unnecessary biopsies and MRIs.

## Contribution

PROSTest is a novel 30-gene mRNA liquid biopsy assay with high diagnostic accuracy for pre-biopsy prostate cancer risk stratification.

## Key findings

- PROSTest achieved 91% overall accuracy and 89% negative predictive value in detecting prostate cancer.
- 47% of men without prostate cancer on biopsy had a negative PROSTest result.
- The test was positive in 91.9% of participants and correctly identified 99% of men with biopsy-confirmed cancer.

## Abstract

This study demonstrates that PROSTest achieves high diagnostic accuracy (>90%) for risk stratification of prostate cancer (PCa) in men undergoing multiparametric MRI and image-guided biopsy. The assay effectively distinguished patients with clinically significant disease from those without histologic evidence of malignancy and was consistently negative in biopsy-negative individuals, supporting a strong negative predictive value. These findings highlight the potential utility of PROSTest as a pre-biopsy triage tool to improve patient selection, reduce unnecessary biopsies, and limit overdiagnosis. Integration of PROSTest into current diagnostic pathways may enhance precision in PCa evaluation and optimize clinical decision-making.

Background/Objectives: Early detection of prostate cancer (PCa) enables timely therapeutic intervention and improved clinical outcomes. Screening strategies are increasingly individualized and now incorporate multiparametric MRI findings, reported using the Prostate Imaging Reporting and Data System (PI-RADS), to refine biopsy decision-making. PROSTest is a novel machine learning (ML)-enhanced, 30-gene mRNA liquid biopsy assay developed to detect PCa from whole blood. In this prospective study (NCT06872619), we evaluated whether PROSTest could function as a pre-biopsy triage tool to inform biopsy decisions while preserving sensitivity for clinically significant prostate cancer (csPCa). Methods: Of 121 men evaluated, 111 (91.7%) completed the full diagnostic work-up—including PSA testing, PROSTest analysis, and PI-RADS assessment—and subsequently underwent image-guided biopsy. Peripheral blood samples for PROSTest were collected prior to biopsy. RNA-stabilized samples underwent RNA isolation followed by reverse transcription and quantitative PCR. Gene expression data were processed using a proprietary machine learning algorithm to generate a continuous range from 0 to 100. A clinically validated cut-off ≥ 50 was applied to produce a binary (positive/negative) result. The diagnostic accuracy of PROSTest was assessed against histology-confirmed prostate cancer. Results: The median age of participants was 69 years (47–83 years) and the median PSA was 7.5 ng/mL (IQR: 5.8–11.4 ng/mL); most patients (104 of 111; 93.7%) had a PI-RADS score of three to five. PCa was diagnosed in 97 men (87.4%) including eight in ISUP Grade Group (GG) 1, 46 in GG2, 33 in GG3, three in GG4 and seven in GG5. PROSTest was positive in 102/111 (91.9%). Among men with biopsy-confirmed PCa, diagnostic accuracy was 99% (93/94). Of the 17 men without histologic evidence of disease, eight (47%) were PROSTest-negative. The overall accuracy was 91% (84.1–95.6%) with an NPV of 89% (51.6–98.4%). Among the nine patients with positive PROSTest but negative biopsy, PI-RADS scores were 4 (n = 6), 3 (n = 1), and 2 (n = 2). Conclusions: PROSTest demonstrated an overall accuracy of 91% (95% CI: 84.1–95.6%) with an NPV of 89%. Among men without a detectable prostate cancer on biopsy, 47% (8/17) were PROSTest-negative. These results suggest that PROSTest may serve as a useful pre-biopsy triage assay.