SUO 2019: Evaluation of Biomarkers 4K Score, SelectMDx and ExoDx™, PSAD, TRUS and MRI for the Detection of High-Grade Prostate Cancer

Washington, DC ( While PSA screening has resulted in decreasing prostate cancer mortality, PSA is also known to be a poorly specific test for the detection of clinically significant cancer and can lead to unnecessary biopsies, over-detection of low risk prostate cancer or even miss aggressive disease. PSA’s lack of robustness as a screening biomarker has led to the development of new prostate cancer screening tools (urine, blood, and imaging-based) to add specificity to PSA for the detection of clinically significant prostate cancer. During the oral abstract session at the 20th Annual Meeting of the Society of Urologic Oncology, Dr. Claire De La Calle and colleagues presented results of their study evaluating and comparing three screening tools in the clinical setting: serum based 4K score and urine based studies SelectMDX and ExoDx™. Their objective was to assess these three study’s added value for the detection of clinically significant prostate cancer when combined with multiparametric parametric MRI (mpMRI).

This study included patients referred to the University of California-San Francisco (UCSF) from 2016 to 2019 for consideration of a prostate biopsy. Exclusion criteria included patients with a PSA >20 ng/mL or patients with a previous positive prostate biopsy, leading to 896 patients that met inclusion criteria. All patients underwent either:

  • Digital rectal examination followed by urine collection for SelectMDx testing
  • Urine collection for ExoDx without pretesting digital rectal examination
  • Serum based 4K score

SelectMDx scores were binary, consisting of low or high-risk for prostate cancer. ExoDx was considered high prostate cancer risk if the IntelliScore was >15.6, and 4K scores were considered high-risk of >10%.

Overall, there were 457 patients that had a prostate biopsy. All biopsies were systematic 14 cores with or without targeted ultrasound or mpMRI fusion cores. The investigators defined the sensitivity, specificity, negative predictive value, and positive predictive value of each biomarker, mpMRI, transrectal ultrasound, and PSA density for the detection of all prostate cancers and specifically high-grade prostate cancer (defined as Gleason grade of 3+4 or higher). Multivariate logistic regression modeling adjusting for age, PSA, prostate volume, digital rectal examination, family history of prostate cancer, and history of prior negative biopsy was performed to determine each biomarker’s ability to predict the presence of any cancer on biopsy or high-grade prostate cancer, with or without imaging.

The mean age of patients undergoing biopsy was 65.5 years (+/- 7.68 years), 70% were Caucasian, 5% were African American, and 88% had no family history of prostate cancer. There were 73% patients that were biopsy naïve and the median PSA was 6.32 ng/mL (IQR 4.76-8.70). ExoDx had the highest sensitivity overall, but the lowest specificity, while SelectMDx had the lowest sensitivity but higher specificity than the other biomarkers for detecting clinically significant cancer. mpMRI with a PIRADs 4 or 5 lesion (or a positive lesion on TRUS) had the highest specificity but sensitivity was considerably lower than 4K or ExoDx sensitivities. Multivariate logistic regression modeling showed that a positive result in any one of the biomarkers or imaging (mpMRI PIRAD 4 or 5 lesion or positive lesion on TRUS) was strongly associated with finding high-grade disease. Furthermore, combining mpMRI with a biomarker increased predictive power for detecting clinically significant cancer. As follows are the results for missed high-grade cancer cases and the number of avoided biopsies:


ExoDx had the highest area under the curve (AUC) for performance in predicting high-grade disease of all the biomarkers (AUC 0.848 for ExoDx versus 0.807 for 4K score and 0.679 for SelectMDx). The addition of a PIRADS 4 or 5 lesion on mpMRI increased the ExoDx AUC to 0.875 (from 0.848) and the 4K score AUC to 0.873 (from 0.807) and the SelectMDx AUC increased to 0.819 (from 0.679).

Dr. De La Calle and her colleagues from UCSF concluded their study with the following conclusions:

  • A 4K score of >10%, or a ExoDx score of >15.6, or a PIRAD 4 or 5 lesion on mpMRI all outperformed PSA density, transrectal ultrasound and SelectMDX for the prediction of high-grade prostate cancer.
  • High 4K scores and high ExoDx scores had high sensitivities while a PIRADS score of 4 or 5 on mpMRI, or positive lesion on TRUS had better specificity for high-grade prostate cancer.
  • Combining the biomarkers with mpMRI resulted in the best predictive ability for detecting clinically significant cancer, increasing the AUC’s of all biomarkers alone.

Presented by: Claire M. De La Calle, MD, Resident Physician, Department of Urology, University of California, San Francisco, San Francisco, California, USA.

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC