For decades, the story of prostate cancer screening has been dominated by three letters: P-S-A. The Prostate-Specific Antigen blood test is the first line of defense for millions of men. Yet, for all its widespread use, the PSA test has a notoriously fraught legacy. It’s a blunt instrument in a field that demands precision. It’s a test that saves lives but also fuels anxiety, triggers painful and sometimes unnecessary procedures, and often can’t tell us how dangerous the lumps are.
About one in eight men will hear the words “you have prostate cancer” in their lifetime. The PSA test, which measures a protein made by the prostate, is how the vast majority of them find out. But this protein can be elevated for many reasons — not just cancer.
Common and benign conditions like an enlarged prostate (BPH) or inflammation (prostatitis) can also send PSA levels soaring. And this leads to a cascade of follow-up actions. This lack of specificity is another problem for the test, leading to a high number of false positives and sending many men for prostate biopsies. And these procedures are invasive and uncomfortable.
Even worse, the PSA test can lead to the over-diagnosis and over-treatment of slow-growing, indolent cancers that might never have caused a problem. So, there are many reasons why we want a better alternative to the PSA. Scientists have looked for new markers in blood and even developed other urine tests, but none have proven to be the flawless diagnostic tool that patients and doctors want.
This is where the new study comes in.
A team of researchers at Johns Hopkins University offers a powerful contender that could revolutionize how we detect the disease. The simple, non-invasive urine test accurately identified prostate cancer 91% of the time, outperforming existing methods.
A Genetic Whisper in the Stream
Instead of looking for a single protein in the blood, the Johns Hopkins team turned their attention to the genetic material shed by cells directly from the prostate into urine. The researchers suspected that prostate cancer cells would shed a unique pattern of RNA messages. This molecular signature would go on to form the base of the new study.
Of course, finding these signatures is easier said than done. The journey began by sifting through the genetic noise. Using advanced RNA-sequencing technology on urine samples from men with prostate cancer and healthy individuals, they initially identified 815 distinct RNA signals that were different between the two groups. To confirm these signals truly originated from prostate tumors, they cross-referenced them with a massive genetic database, The Cancer Genome Atlas, and found that 95% of the upregulated genes were indeed elevated in prostate tumor tissue.
This was a promising route, but too broad a signal. So, the researchers narrowed it down to the 50 most promising candidates. After testing, a powerful trio of biomarkers emerged: three RNA molecules named TTC3, H4C5, and EPCAM. TTC3 appears to play a role in the cancer’s growth, and when researchers blocked TTC3 in prostate cancer cells in the lab, the cells’ ability to invade other tissues was significantly suppressed.
This was a bonus. They didn’t just find a marker, they found a potential driver of the disease itself.
Creating the Test
The team then combined these three markers into a single, powerful “signature” they could detect. They designed a large study involving hundreds of men. The men were split into a “development” group that would fine-tune the test, and a “validation” group that would confirm the results. The participants provided a simple urine sample and nothing else.
Scientists use a metric called “area under the curve” or AUC to assess how well the test performed. An AUC of 1 is a perfect test; an AUC of 0.5 is like a coin toss. In the first group of 243 men, they achieved an AUC of 0.96, remarkably close to perfect. For the larger, validation group of 646 men, they achieved an AUC of 0.92.
In other words, the approach demonstrated a sensitivity (the ability to correctly identify men with cancer) of 94% and a specificity (the ability to correctly identify men without cancer) of 86% in the first group and 91% sensitivity and 84% specificity in the second. In essence, the test was both an excellent detector and a reliable screener, catching the disease when present and reassuring men when it was not.
Importantly, the test also demonstrated a powerful ability to distinguish between prostate cancer and the benign conditions that the PSA test sometimes mistakes for cancer. This specificity is the key to reducing unnecessary biopsies. A doctor equipped with this test could more confidently tell a patient that his elevated PSA is likely due to a benignly enlarged prostate, saving him from a painful and unnecessary procedure.
Promising Progress
“This new biomarker panel offers a promising, sensitive and specific, noninvasive diagnostic test for prostate cancer,” says senior study author Ranjan Perera, Ph.D., director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and a professor of oncology and neurosurgery at the Johns Hopkins University School of Medicine. “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.”
The implications are profound. This urine-based panel represents a potential paradigm shift in prostate cancer diagnostics. It opens the door to a more accurate, less invasive, and less anxiety-inducing screening process. It could help doctors better select which men truly need a biopsy, catch aggressive cancers earlier (even with a low PSA), and monitor patients for recurrence after treatment.
“There is a real need for non-PSA-based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic,” says study co-author Christian Pavlovich, M.D., the Bernard L. Schwartz Distinguished Professor of Urologic Oncology at Johns Hopkins and program director for the Prostate Cancer Active Surveillance Program. “Most urologists feel that an accurate urinary biomarker would be a valuable addition to our current diagnostic armamentarium.”
“This test has the potential to help physicians improve diagnostic accuracy of prostate cancer, reducing unnecessary interventions while allowing early treatment for those who need it,” says study co-author Vipul Patel, M.D., director of urologic oncology at AdventHealth Cancer Institute in Celebration, Florida. Patel also is medical director of global robotics for AdventHealth’s Global Robotics Institute, and founder of the International Prostate Cancer Foundation. “On behalf of physicians and patient globally, I advocate for further study and progress for these biomarkers.”
More Work to Be Done
Yet, the road from a promising study to a routine clinical test is still long. The researchers rightly note that larger, prospective trials are needed to validate its performance in broader populations and establish its definitive role in clinical decision-making.
But the foundation laid here is exceptionally strong. In the long and often frustrating search for a better way to find prostate cancer, this three-marker “liquid biopsy” stands out as a triumph of modern molecular science and a tangible reason for optimism.
The study was published in the journal eBio Medicine.
