Personalized Prostate Cancer Risk Assessment With an Integrated Biomarker and Magnetic Resonance Imaging Approach

By: David M. Albala, MD, Crouse Hospital, Syracuse, New York, Associated Medical Professionals, Syracuse, New York, Downstate Health Sciences University, Brooklyn, New York | Posted on: 06 Jul 2023

In recent years, urologists and patients with prostate cancer have benefited tremendously from innovations in cancer detection and risk assessment, most notably the development and validation of genomic biomarkers that are more specific and informative than the old standby of PSA. These new biomarker tools have helped to better stratify the patients that need a biopsy and focused on men with clinically significant prostate cancer.

However, there is still a need for genuinely personalized risk assessments for each patient to ensure that invasive procedures such as biopsies are performed when necessary—and are never missed when men at higher risk should have one. Recent studies have shown that combining biomarker testing with multiparametric MRI (mpMRI) may address this issue. This integrated approach is still under evaluation, and specific strategies will be needed to help urologists implement it effectively for patients.

While there are several techniques for biomarker testing in patients with suspected prostate cancer, many urologists have turned to exosome-based testing because it is noninvasive and supported by strong clinical validation and utility evidence.

Exosomes can be thought of as cellular tweets: these vesicles are released by the thousands from all cells, and they contain RNA, DNA, and proteins intended as messages to other cells. They are tiny, on the scale of a virus, and present in all biofluids. Because they represent messages sent from cells throughout the body, they overcome the challenges of tissue heterogeneity that limit tissue-based biomarker tests.

The ExoDx Prostate Test, also called EPI (Exosome Diagnostics, Waltham, Massachusetts), is a noninvasive, urine-based risk assessment tool designed to identify men most likely not to have high-grade prostate cancer (HGPCA) found at biopsy. The test extracts genomic information from exosomes found in urine and reports the results of 3 prostate-related biomarkers: ERG, PCA3, and SPDEF. Data from those biomarkers are calculated and presented to physicians and patients in a risk score from 0 to 100. The higher the score, the higher the likelihood of HGPCA. A digital rectal exam is unnecessary in this process.

The ExoDx Prostate Test is usually indicated when considering a biopsy for men aged 50 or older with a PSA of 2-10 ng/mL. While no prostate cancer test is binary, this test provides useful risk assessment information that can increase compliance with a biopsy recommendation for high-risk patients while easing the minds of low-risk patients when they and their physicians agree to defer biopsy.

In several peer-reviewed studies spanning more than 3,400 patients—including prospective, randomized, blinded trials—evidence demonstrates that when the ExoDx Prostate Test is used as indicated, it can reduce biopsies unlikely to find HGPCA.1,2 Results also point to the accuracy of the test, indicating that patients identified as high-risk are on average 3 times more likely to have HGPCA than low-risk patients, and that patients deemed to be low-risk were indeed very unlikely to develop serious cancer. In a randomized, blinded, double-arm, clinical utility trial, the test risk score led to increased patient compliance with biopsy recommendations and found 30% more HGPCA than in the standard-of-care arm.3 Generally, patients with a risk score of 15.6 or less can safely avoid biopsies, and men with higher risk scores are more likely to find HGPCA as the test score increases.4

As no digital rectal exam is required, a recent addition to the ExoDx Prostate Test is a home collection kit that allows patients to capture their urine samples from the comfort and privacy of their homes, whenever it is most convenient for them. The home collection kit was helpful to many urologists during the pandemic and continues to be preferred by many patients over in-clinic collection.

Because all risk stratification tools have individual strengths and limitations, a complementary approach using biomarker testing and MRI may provide a stronger and more personalized clinical assessment. Recently, urologists have begun evaluating the impact of pairing mpMRI with biomarker testing for prostate cancer cases.

Understanding how mpMRI and biomarker testing can be integrated into the prostate cancer diagnostic algorithm is vital. Specific strategies are still under evaluation—such as the utility of performing an MRI or the biomarker test up-front—but early evidence is promising.

MRI is now a standard tool for prostate cancer assessment, but it is better in some instances than others. For example, as tumor size increases, the likelihood of detecting it with MRI is excellent. However, for small tumors, that likelihood decreases dramatically. Also, data have shown that MRI catches most index tumors, missing just 20% to 30% of them, but it cannot detect most nonindex tumors, missing as many as 70% of them.5 The negative predictive value of MRI testing is low enough that a negative MRI cannot reliably indicate that there is no cancer. In fact, the AUA updated the Prostate Cancer Early Detection guidelines and emphasized that a negative MRI result should still have a systematic biopsy for initial biopsy decisions.6,7 Despite these challenges, including MRI to complement other methods can offer a more robust assessment tool.

In small studies, pairing mpMRI with the ExoDx Prostate Test improves the accuracy of risk assessment for patients with prostate cancer. According to the data, integrating the tests almost eliminates the chances of missing cases of HGPCA.8

One possible integrated strategy could be to start with the ExoDx Prostate Test. If the risk is 15.6 or less, the patient might not need additional testing or a biopsy. Risk scores between 15.6 and 19 indicate the need for an MRI before deciding whether to proceed with a biopsy. Risk scores above 19 indicate a biopsy without needing an additional MRI test.9

Larger studies of this integrated approach—including several different strategies for when and how to pair the tests—will be essential for demonstrating its value and for showing urologists how best to implement it in their practice. What is clear already is that exosome-based testing and mpMRI offer a tantalizing opportunity to improve risk stratification and achieve more personalized recommendations for each patient.

  1. McKiernan J, Donovan MJ, O’Neill V, et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol. 2016;2(7):882-889.
  2. McKiernan J, Donovan MJ, Margolis E, et al. A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/ml at initial biopsy. Eur Urol. 2018;74(6):731-738.
  3. Tutrone R, Donovan MJ, Torkler P, et al. Clinical utility of the exosome based ExoDx Prostate (IntelliScore) EPI test in men presenting for initial biopsy with a PSA 2–10 ng/mL. Prostate Cancer Prostatic Dis. 2020;23(4):607-614.
  4. Margolis E, Brown G, Partin A, et al. Predicting high grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies. Prostate Cancer Prostatic Dis. 2022;25(2):296-301
  5. Stabile A, Dell’Oglio P, De Cobelli F, et al. Association between prostate imaging reporting and data system (PI-RADS) score for the index lesion and multifocal, clinically significant prostate cancer. Eur Urol. 2018;1(1):29-36.
  6. Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. 2023;210(1):46-53.
  7. Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part II: considerations for a prostate biopsy. J Urol. 2023;210(1):54-63.
  8. Kretschmer A, Skog J, Fischer C, et al. PD11-08 A combined biomarker/mpMRI approach provides enhanced clinical information prior to prostate biopsy. J Urol. 2022;207(5 Suppl):e193.
  9. de la Calle CM, Fasulo V, Cowan JE, et al. Clinical utility of 4Kscore®, ExosomeDx and magnetic resonance imaging for the early detection of high grade prostate cancer. J Urol. 2021;205(2):452-460.