Use of the MyProstateScore Test to Rule Out Clinically Significant Cancer: Validation of a Straightforward Clinical Testing Approach

Purpose: The MyProstateScore test was validated for improved detection of clinically significant (grade group ≥2) prostate cancer relative to prostate specific antigen based risk calculators. We sought to validate an optimal MyProstateScore threshold for clinical use in ruling out grade group ≥2 cancer in men referred for biopsy.

Materials and Methods: Biopsy naïve men provided post-digital rectal examination urine prior to biopsy. MyProstateScore was calculated using the validated, locked multivariable model including only serum prostate specific antigen, urinary prostate cancer antigen 3 and urinary TMPRSS2:ERG. The MyProstateScore threshold approximating 95% sensitivity for grade group ≥2 cancer was identified in a training cohort, and performance was measured in 2 external validation cohorts. We assessed the 1) overall biopsy referral population and 2) population meeting guideline based testing criteria (ie, prostate specific antigen 3-10, or <3 with suspicious digital rectal examination).

Results: Validation cohorts were prospectively enrolled from academic (977 patients, median prostate specific antigen 4.5, IQR 3.1–6.0) and community (548, median prostate specific antigen 4.9, IQR 3.7–6.8) settings. In the overall validation population (1,525 patients), 338 men (22%) had grade group ≥2 cancer on biopsy. The MyProstateScore threshold of 10 provided 97% sensitivity and 98% negative predictive value for grade group ≥2 cancer. MyProstateScore testing would have prevented 387 unnecessary biopsies (33%), while missing only 10 grade group ≥2 cancers (3.0%). In 1,242 patients meeting guideline based criteria, MyProstateScore ≤10 provided 96% sensitivity and 97% negative predictive value, and would have prevented 32% of unnecessary biopsies, missing 3.7% of grade group ≥2 cancers.

Conclusions: In a large, clinically pertinent biopsy referral population, MyProstateScore ≤10 provided exceptional sensitivity and negative predictive value for ruling out grade group ≥2 cancer. This straightforward secondary testing approach would reduce the use of more costly and invasive procedures after screening with prostate specific antigen.

Jeffrey J. Tosoian, Bruce J. Trock, Todd M. Morgan, Simpa S. Salami, Scott A. Tomlins, Daniel E. Spratt, Javed Siddiqui, Lakshmi P. Kunju, Rachel Botbyl, Zoey Chopra, Balaji Pandian, Nicholas W. Eyrich, Gary Longton, Yingye Zheng, Ganesh S. Palapattu, John T. Wei, Yashar S. Niknafs, and Arul M. Chinnaiyan.

Urologic Oncology, Department of Urology, The University of Michigan, Ann Arbor, Michigan; Johns Hopkins Brady Urological Institute, Baltimore, Maryland; Department of Urology, University of Michigan, Ann Arbor, Michigan, Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Biostatistics Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

A limited subset of this analysis was presented in abstract form at the Early Detection Research Network (EDRN) Scientific Workshop, Bethesda, Maryland, September 10, 2019.

Supported by the Prostate Cancer Foundation, Early Detection Research Network (UO1 CA214170), NCI Prostate SPORE (P50 CA186786), and an NCI Outstanding Investigator Award (R35CA231996).

JJT, YSN and AMC are co-founders and have equity in LynxDx, which has licensed the urine biomarkers mentioned in this study from Hologic and the University of Michigan. JJT and YSN have leadership roles in Lynx Dx and AMC serves on the scientific advisory board. The University of Michigan has been issued a patent on ETS gene fusions in prostate cancer on which AMC and SAT are co-inventors. The diagnostic field of use has been licensed to LynxDx. BJT has received research funding from MDxHealth and Myriad Genetics. SAT serves as CMO of Strata Oncology which was not involved in this study. LynxDx or Strata Oncology did not fund the conduct of this study.

References 31 through 36 can be obtained at https://www.jurology.com.

© 2021 by American Urological Association Education and Research, Inc.

Source: "Use Of The Myprostatescore Test To Rule Out Clinically Significant Cancer: Validation Of A Straightforward Clinical Testing Approach | Journal Of Urology". 2022. Journal Of Urology. 
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