Originally published 8/29/2022
Researchers continue to test ways to surmount the shortcomings of standard PSA screening, which can lead to immediate biopsy with its record of overdiagnosis; many biopsies turn out to have been unnecessary. While no one has yet developed a PCa-specific liquid biopsy (blood draw or urine test), a new 18-gene urine test is promising. It can accurately identify high-grade PCa, thus showing which men need biopsy while reducing the burden of further testing for those who don’t. In a cohort of over 700 men, the team conducted comparison analyses of the new test, called MPS2, vs. existing biomarker tests and risk calculators. At 95% sensitivity for high-grade PCa, the MPS2 test outperformed any other single existing biomarker test. The authors write, “Clinically, the use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers.” Although it’s not quite a liquid biopsy, the use of theMPS2 urine test following a suspicious PSA would lessen the harms of screening while preserving its long-term benefits.[i]
Your car’s check engine light is a big uh-oh. If it comes on, you probably groan internally. It means taking time out of your busy life to get to a mechanic who can put your car on a computer (possibly for a fee) to access a diagnostic code. But that’s just the first step. Now the mechanic asks when it started, is it on constantly or is it sporadic, and whether you’ve noticed any performance problems since it came on. Next comes troubleshooting. Was it just a loose gas cap? Perhaps it’s a malfunctioning sensor or a spark plug issue. What if you need a new catalytic converter? If only your car’s computer could have assembled and assessed all the necessary bits of information in one easy step! It would spare you from time-consuming and potentially expensive steps.
When it comes to prostate cancer (PCa), your body comes equipped with a kind of check engine light. It’s your PSA blood test. If it comes back abnormally high or rising, it’s a physical uh-oh. Like a check engine light, it doesn’t tell you exactly what the problem is. A doctor’s next step might well be a conventional 12+ core TRUS biopsy, with its risks of inaccuracy and side effects. What if there were a simpler way to assemble and evaluate vital information in a single step, such as a blood draw?
A June, 2022 review article in the British Journal of Cancer synthesizes a large body of recent research on blood-based biomarkers for PCa.[ii] Biomarkers are bits of cellular and molecular information that can be collected at any stage of the disease, and assembled like clues in a detective novel. They can potentially be used for better screening than a nonspecific PSA blood test, for characterizing the danger level of a patient’s PCa cell line, and to develop customized treatment plans for localized, advanced, or metastatic PCa.
According to the authors, “there has been an interest in blood-based biomarkers, commonly referred to as liquid biopsies… as an alternative or companion to solid tumour biopsies and imaging studies to better characterise tumour molecular drivers and response to treatment.” PCa clues that circulate in the blood include proteins, cells, molecules called nucleic acids (DNA, RNA), and extracellular vesicles that are like packets of molecular information. There are also intact tumor cells that circulate in the blood, which can not only be counted (the number itself says something about disease aggressiveness) but which also contain molecular information. It is a sort of scientific miracle that that today’s advanced collection methods that can isolate these diagnostic resources from a blood draw. Laboratory analysis identify genomic patterns and alterations that round out a profile of a patient’s disease, based on such factors as circulating cell-free DNA, tumor-derived DNA, etc.
We’re not yet at the point where a commercially available blood analysis for PCa exists. The authors explain current technologic shortcomings or obstacles to its development. The goal is lofty. According to the article, a good PCa liquid biopsy should accomplish the following, which encompasses all PCa stages:
guide one or more clinical decision points such as diagnosis, molecular characterisation and risk stratification in an early setting, detection of early relapses, treatment cessation or intensification and identification of mechanisms of resistance to current treatments in the metastatic setting.
We are on the road to molecular profiling using a one-stop-shop blood draw, and we’re getting closer to setting up meaningful clinical trials needed for watchdog approvals. For more information, check out my blog on how liquid-based biomarkers could help avoid overtreatment.
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.
References
[i] Tosoian JJ, Zhang Y, Xiao L, et al. Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer. JAMA Oncol. Published online April 18, 2024.
[ii] Trujillo B, Wu A, Wetterskog D, Attard G. Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges. Br J Cancer. 2022 Jun 17. doi: 10.1038/s41416-022-01881-9. Epub ahead of print. PMID: 35715640.
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.
