Sperling Prostate Center

How Can Liquid Biomarkers Reduce Prostate Cancer Overtreatment?

“There is always a well-known solution to every human problem—neat, plausible, and wrong.” This quote from humorist H. L. Mencken might well apply to the latest government recommendation regarding PSA screening. Since its development and wide availability starting in the late 1990s, this simple blood test has undoubtedly saved the lives of hundreds of thousands of men whose prostate cancer (PCa) would have gone undetected until it was too late to cure it. Sounds good, right? The problem is, countless men were over-biopsied and over-treated because the test doesn’t give enough information.

How to get more specific

When the U.S. Preventive Services Task Force (USPSTF), a government advisory panel, downgraded the importance of PSA screening, it seemed like a neat, plausible solution to the problem. But subsequent statistics began to emerge that showed the solution was wrong! At first, the number of newly diagnosed cases began to drop. This didn’t mean there was less PCa, it meant we weren’t looking for it. (Duh!) By the time it was discovered, often incidentally as part of other exams or tests, it was at a more aggressive stage.

So, in 2018, the USPSTF revised their position, suggesting that men ages 55-69 talk with their doctors to make individual informed decisions about whether or not to screen. This, too, is not a simple, plausible solution. Our position all along has been that annual PSA screening is the best policy provided that more specific information accompanies it.

In our experience, when PSA results are suspiciously high or rising, multiparametric MRI (mpMRI) reveals if there is an area that would benefit from an in-bore, MRI-guided targeted biopsy. Overall, mpMRI separates the sheep from the goats, that is, it “overlooks few prostate cancers, and these tend to be smaller and less aggressive than cancer that is detected.”[i] This is a simple, plausible and RIGHT solution to the problem. mpMRI of the prostate complements the PSA test by providing a highly specific 3-dimensional portrait of the gland and its environment.

Liquid biomarkers

There is an additional and fairly recent way to obtain specific information to round out a PSA-based red flag. This approach utilizes what are called liquid biomarkers. These are cancer clues in the form of physical evidence in bodily fluids that circulate. “Tumor cells, tumor-derived metabolites, proteins, nucleic acids and vesicles are constantly shed into the circulation and these circulating components can provide valuable diagnostic, prognostic and predictive information.”[ii] This means tumor cancers such as PCa send out a sort of encoded message regarding their presence and characteristics—if only we can capture and decode it. This is beginning to transform cancer diagnosis, but there’s a catch: “the technique is not yet a standard tool in the clinical oncologist’s arsenal.”[iii]

Using liquid biomarkers for PCa early detection

That situation is changing in the urologic use of liquid biomarkers. Urologic oncologist Judd W. Moul, MD supports the continued use of PSA as a screening tool. He points out, however, that both blood and urine can now be analyzed for more specific information that permits early detection of PCa in order to warrant a biopsy. It’s not just doctors who are embracing the advance of liquid biomarkers, as Moul explains: “After a standard PSA test indicates that PSA level is elevated, borderline, or in the “gray zone,” many patients request more data before they undergo an invasive tissue biopsy.”[iv]

Thus, liquid biomarkers can clarify if a suspicious PSA is actually an indication of PCa. This means unnecessary biopsies can be avoided, thereby reducing both overdetection and overtreatment of insignificant disease.

Dr. Moul and his colleagues also recognize the value of top-quality mpMRI by experienced radiologists, especially for planning a targeted biopsy. No matter how informative liquid biomarkers are, the definitive diagnosis of prostate cancer can only be obtained by tissue samples from biopsy. And the most accurate, and least invasive, targeted biopsy is a real-time in-bore MRI-guided biopsy.

A multi-level approach to detecting and diagnosing PCa that spares men from overtreatment is now possible, thanks to PSA, liquid biomarkers, and mpMRI.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Norris JM, Simmons L, Kanthabalan A, Freeman A et al. Which Prostate Cancers are Undetected by Multiparametric Magnetic Resonance Imaging in Men with Previous Prostate Biopsy? An Analysis from the PICTURE Study. Eur Urol Open Sci. 2021 Jun 15;30:16-24.
[ii] Lim SY, Lee JH, Diefenback RJ, Kefford RF, Rizos H. Liquid biomarkers in melanoma: detection and discovery. Mol Cancer. 2018; 17: 8
[iii] Alix-Panabières, Catherine. “Outlook: The future of liquid biopsy”. Nature. Mar. 25, 2020. https://www.nature.com/articles/d41586-020-00844-5
[iv] Albala D, Moul JW. “Uroview: The Role of Liquid Biomarkers for the Early Detection of Prostate Cancer.” Urology Times. July 19, 2021.


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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