Urine-Based Gene Expression Assay Helps Identify High-Grade Prostate Cancer

Noninvasive test could help reduce the total number of biopsies in men suspected of having prostate cancer

medwireNews: A noninvasive assay measuring the expression of three exosome genes discriminates high-grade prostate cancer from low-grade and benign disease in men with equivocal prostate-specific antigen (PSA) levels at initial biopsy, research suggests.

Use of this urine-based test “may reduce and/or delay unnecessary biopsies for most men” with a suspicion of prostate cancer, say Michael Donovan, from Icahn School of Medicine at Mount Sinai in New York, USA, and co-researchers.

They evaluated the assay in a training cohort of 255 men aged 50 years or older who were scheduled to undergo an initial prostate needle biopsy on the basis of suspicious digital rectal examination results and/or PSA levels between 2 and 10 ng/mL, and validated it in a cohort of 519 men.

The ExoDx Prostate IntelliScore assay measures the urinary exosomal expression of the ERG, PCA3 and SPDEF genes, which are “known to play a role in prostate cancer initiation and progression”, explain the authors.

Together with standard of care, which takes into account PSA level, age, ethnicity and family history, the assay discriminated patients with high-grade disease (Gleason Score [GS]≥7) from those with GS 6 and benign disease with an area under the receiver operating characteristic curve (AUC) of 0.77 in the training cohort and 0.73 in the validation cohort. This was significantly better than with standard of care alone, which had an AUC of 0.66 and 0.63 in the training and validation cohorts, respectively.

At a prespecified cutoff of 15.6, the assay alone discriminated high-grade disease from low-grade and benign disease with a sensitivity of 91.89%, a specificity of 33.96%, a positive predictive value of 35.70% and a negative predictive value of 91.30% in the validation cohort.

The researchers report in JAMA Oncology that using this cutoff 27% of initial biopsies would have been avoided but that 8% of high-grade cancers would have been missed. Of these 12 missed cases, nine had less than a third of cores involved but three patients had dominant GS pattern 4 high-risk disease.

In an accompanying editorial, Hiten Patel, from James Buchanan Brady Urological Institute in Baltimore, Maryland, USA, and co-authors say that “[t]he performance of the 3-gene expression assay in a random sample of men not scheduled for biopsy is unknown, making it uncertain whether the assay holds promise as an independent screening modality.”

But they believe that if validated, the assay holds promise as “a secondary or reflex test for risk stratification in the setting of exercising stewardship with PSA screening, […] rather than as a means of completely stopping PSA screening.”


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; Advance online publication 31 March. doi: 10.1001/jamaoncol.2016.0097

Patel HD, Chalfin HJ, Carter B. Improving prostate cancer screening and diagnosis. Health policy and biomarkers beyond PSA.JAMA Oncol 2016; Advance online publication 31 March. doi: 10.1001/jamaoncol.2016.0170

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