PROSTest, a Novel Liquid Biopsy Molecular Assay, Accurately Guides Prostate Cancer Biopsy Decision-Making in Men with Elevated PSA Irrespective of DRE Findings

Document Type

Article

Publication Date

12-6-2025

Publication Title

Cancers (Basel)

Keywords

DRE; PROSTest; PSA; biopsy; prostate cancer; stratification

Abstract

Background/Objectives: Elevated PSAs combined with an abnormal digital rectal examination (DRE) are strong indicators of the possibility of a prostate cancer (PCa) and are used to guide biopsy decisions. We evaluated whether PROSTest, a novel, clinically validated, blood-based multigene mRNA test could aid in biopsy decision-making irrespective of DRE results in subjects ≥45 years with PSA ≥ 3 ng/mL.

Methods: A retrospective cohort analysis was performed with a prespecified statistical analysis plan to test the null hypothesis that an abnormal DRE does not materially affect the sensitivity, specificity, or overall stratification performance of PROSTest. The pool included 327 subjects aged ≥45 years with abnormal PSA (≥3 ng/mL) who had undergone DRE and prostate biopsy. Diagnostic performance of PROSTest (measured pre-biopsy) was evaluated within two PSA strata (3-10 ng/mL and >10 ng/mL) and compared to DRE in the same strata. Metrics including sensitivity, specificity, positive and negative predictive values, and accuracy were calculated.

Results: Among 327 subjects, 215 had PSA 3-10 ng/mL and 112 had PSA > 10 ng/mL. A total of 131 cancers (40.1%) were diagnosed. PROSTest achieved high sensitivity (93.9-96.6%), specificity (82.4-92.7%), and overall accuracy (up to 94.1%) across all DRE/PSA combinations. The DRE+/PROSTest+ group demonstrated similarly high sensitivity (96.6%) and specificity (92.7%), comparable to the DRE-/PROSTest+ group. Multivariate analysis confirmed PROSTest as an independent predictor of PCa (OR: 154, p < 0.0001), outperforming DRE.

Conclusions: PROSTest provides highly accurate risk stratification in men with elevated PSA, independent of DRE findings and may be used with PSA to much more effectively guide biopsy decisions.

PubMed ID

41463159

Volume

17

Issue

24

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