Originally published: November 19, 2021
Stop the presses! Researchers at the University of Michigan (U of M) may be like the young King Arthur who pulled the magic sword Excalibur from its locked place in a huge stone. Until now, the most common biomarker screening test for prostate cancer (PCa) has been the PSA blood test—which is notoriously imperfect. Too many men have unnecessarily undergone needle biopsies based only on suspicious PSA results. Clinicians have long sought a “magic” screening test that would be so simple yet so precise that it could tell if a biopsy is warranted or not. The search may be over as of a June, 2024 published study of a simple urine test which screens for 18 genetic markers link with clinically significant prostate cancers. By performing a gene analysis of over 58,000 genes, the U of M team ultimately identified 17 biomarkers uniquely overexpressed by high-grade cancers.[i] Through testing and validation, they showed that this new test, called MPS2, outperformed previous tests (PSA alone, two risk calculators, the derived multiplex 2-gene and 3-gene models, and the previous 2-gene MPS test) in diagnostic accuracy for high-grade PCa at 95-99%! The clinical consequences of this “magic screening sword” for men suspected of having PCa are huge. In congratulating the developers, we like U of M’s team rallying cry, “GO BLUE!”
If you were awakened from a sound sleep by a suspicious noise somewhere outside your closed bedroom door, would you grab a gun from your nightstand and start blasting bullets through the wood? It’s scary to be startled awake, but you need correct information ASAP before you pull the trigger. Was it the rumble of an approaching storm? Your child knocking on the bedroom door for some reassurance after a nightmare? Your lonely golden lab bumping on the door to be admitted? Why blow the wood to shreds—possibly endangering an innocent—before you have the correct facts?
As grim as that imaginary scenario is, it’s a metaphor for what clinical practice has been doing to the prostate gland and a man’s quality of life for decades. The initial “noise” that “wakes you up” is the PSA test used as a screening tool for prostate cancer (PCa). Since the mid-1990s, a suspicious result of a blood draw has been the first wake-up call along a diagnostic pathway for PCa.
The PSA test has saved countless lives, but over the years it’s become clear that it’s an imperfect screening tool. True, it’s a clue something is irritating the prostate, but it can’t open the door to reveal if there’s a dangerous home invader or not. Doctors’ best hopes for their patients were bullets through the door: unnecessary systematic biopsies and aggressive whole-gland treatments. Some of those bullets left men with wounds in their quality of life: wearing pads or diapers, struggling to have sex, or enduring embarrassing bowel problems. Until recently, these sad consequences of PCa overdetection and overtreatment occurred because doctors only gained information from the PSA test, digital rectal exam, and transrectal ultrasound (TRUS) imaging. Those tools do not give all the correct facts.
Thankfully, the days of shooting through a closed door are coming to an end. New blood and urine tests, and multiparametric MRI (mpMRI) imaging enhanced by Artificial Intelligence (AI), are providing efficient and precise information. We can now quickly gain factual answers to the three most important questions before a needle biopsy:
- Does this man have biological evidence of cancer?
- Can we noninvasively rate the probability that it is significant PCa, i.e., will it need to be treated?
- Can we pinpoint the location, size and shape of the suspicious area for a less invasive yet more accurate targeted biopsy?
Biomarkers as the first clue
The most accurate screening pathway for PCa starts with a biomarker followed by mpMRI. A cancer biomarker can be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. PSA alone is not 100% accurate as a PCa biomarker because any prostate abnormality or activity can cause prostate cells (including PCa cells) to “shed” more antigen than usual. Over a decade ago, a number of blood biomarkers and a new urine marker called PCA3 were identified.[ii] Since then, a growing number of genomic analyses offer PCa-specific information based on a blood draw or urine test. The next step is mpMRI. Like Superman’s x-ray vision, it noninvasively reveals what’s behind the closed door.
Only then can a determination be made if a needle biopsy is warranted. In fact, the PRECISION trial showed that men with no MRI-identified clinical PCa do not need to be biopsied.
Swedish researchers announce a new screening blood test
In early August 2021, the journal Lancet Oncology published results of a new screening blood test called the Stockholm3. It analyzes for the presence of five biomarkers in a blood sample. The authors write:
Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures…and fewer biopsy procedures. Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers, … lower detection of low-grade cancers, … and led to fewer biopsy procedures.[iii]
This study adds to the published literature demonstrating that biomarkers coupled with mpMRI can eliminate “bullets through the door” when PSA makes a “soft noise” of warning. The study merited the positive news stories that followed its publication.
However, one report was a bit concerning since the author interpreted that the new blood test used for screening “can reduce unnecessary MRI scans by 36%…”[iv] She even included “unnecessary MRI” in the title of her piece. This is unfortunate for two reasons: first, the reduced number of MRIs performed was a product of the authors’ confidence that if MRI does not reveal clinically significant disease, foregoing a scan is up to the clinician’s judgment (it may also be influenced by considerations of cost and time burden); second, including a scan is an important way to confirm the indications of the biomarker test.
As of this writing, no biomarker test is 100% diagnostic for prostate cancer, so corroborating test results with imaging is still needed. The Swedish study was labor-intensive. In her review of it, Caroline Moore, MD (University College London) remarked that the protocol used for the research “is markedly more challenging than standard transrectal ultrasound-guided biopsy … Implementation requires a coordinated approach across multiple departments, including imaging, urology, and histopathology…” By its nature, obtaining corroboration is expensive and time-consuming, as is all high-level research.
Our knowledge of excellence and accuracy in PCa screening is evolving. We need such studies to improve men’s health, and ultimately save lives and quality of life. The day is coming when all cancer, including prostate cancer, can be efficiently and painlessly diagnosed early when it is most treatable. For now, biomarkers plus MRI offer the best screening pathway.
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, Xie C et al. Development and Validation of an 18-Gene Urine Test for High-Grade
Prostate Cancer. JAMA Oncol. 2024 Jun 1;10(6):726-736. doi: 10.1001/jamaoncol.2024.0455.
[ii] Makarov DV, Loeb S, Getzenberg RH, Partin AW. Biomarkers for prostate cancer. Annu Rev Med. 2009;60:139-51.
[iii] Nordström T, Discacciati A, Bergman B, Clements M et al. Prostate cancer screening using a combination of risk-prediction, MRI, and targeted prostate biopsies (STHLM3-MRI): a prospective, population-based, randomised, open-label, non-inferiority trial. Lancet Oncol. 2021 Aug 12;S1470-2045(21)00348-X.
[iv] Yee, KM. “New blood test for prostate cancer screening reduces unnecessary MRI.” AuntMinnie.com, Aug. 12, 2021. https://www.auntminnie.com/index.aspx?sec=sup&sub=mri&pag=dis&ItemID=133224
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.
