Novel Urine-Based Test Detects Prostate Cancers

Prostate cancer is one of the leading causes of death in men in the US and is usually detected through prostate-specific antigen (PSA) blood tests. However, PSA is not very specific, meaning many men undergo invasive biopsies that are often negative and carry risks. In addition, PSA testing can lead to overtreatment of low-grade cancers. Now, researchers have identified biomarkers in urine that can accurately detect prostate cancer and reduce unnecessary procedures.

A team at Johns Hopkins Medicine (Baltimore, MD, USA) working with several partner institutions has developed a urine-based test using three biomarkers: TTC3, H4C5, and EPCAM. These markers were present in patients with prostate cancer but nearly absent after prostate-removal surgery, confirming their origin in prostate tissue. The test analyzes RNA extracted from prostate cells shed in urine using RNA sequencing, qPCR, and immunohistochemistry to validate expression patterns.

In development and validation studies using over 1,300 urine specimens, the test achieved an area under the curve (AUC) of 0.92, correctly identifying prostate cancer 91% of the time and ruling out non-cancer cases 84% of the time. The results, published in eBioMedicine, show that it also distinguished prostate cancer from benign conditions such as BPH and prostatitis, outperforming PCA3.

The test showed strong diagnostic accuracy even in PSA-negative patients, maintaining performance of 78.6% and 85.7% across cohorts. By distinguishing cancer from benign conditions and detecting cases with normal PSA levels, it could complement or even surpass PSA screening. Researchers plan to further develop the assay for clinical use, explore its integration with PSA as a “super PSA,” and test it independently at other institutions before broader deployment.

“This new biomarker panel offers a promising, sensitive and specific, noninvasive diagnostic test for prostate cancer,” said Ranjan Perera, Ph.D., senior study author. “It has the potential to accurately detect prostate cancer, reduce unnecessary biopsies, improve diagnostic accuracy in PSA-negative patients, and serve as the foundation for both laboratory-developed and in vitro diagnostic assays.”

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