A 58-year old guy walks into his doctor’s office for his annual wellness check. At some point, the doc says, “Let’s talk about a PSA blood test.” Many men may wonder what’s there to talk about? Well, the latest guidelines recommend that men ages 55-69 make individualized decisions by discussing the possible harms and benefits of this test. Despite its record for too many follow-on biopsies leading to too much overdetection of insignificant prostate cancer (PCa), the old standby PSA is still the cheapest, easiest screening tool.

I have posted numerous blogs about problems with the test due to its limitations. It doesn’t always mean cancer is present because it’s not specific enough. It could mean any number of non-malignant things. Because of this, clinicians have long been seeking ways to boost PSA accuracy using extra ways to analyze the same blood sample. These are called PSA variants, and they include:

• Percent-free PSA
• Complexed PSA
• PSA density
• PSA velocity

Combining one or more of these variants with a standard PSA enriches the information it provides. This helps increase the likelihood that the test results really mean PCa vs. a noncancerous condition such as BPH or an infection. Still, urologists tend to err to the side of doing a biopsy if the results are suspicious. Many of these biopsies turn out to have been unnecessary.

Genetically adjusted PSA

Now, a team of researchers from respected coast-to-coast academic and clinical centers has published a study called Precision PSA.^[i] Their goal was to identify and eliminate genes NOT connected with PCa, thereby increasing likelihood of correctly identifying markers attributable to PCa. They succeeded in raising the predictive value of a PSA test. They reasoned that “… Incorporating additional genetic predictors has the potential to personalize PSA testing, reduce overdiagnosis-related morbidity and improve detection of lethal disease.”

One way to think of it is imagining a café counter on which there are 100 mugs holding a dark brown liquid. You want tea, but 98 contain coffee. One way to find your tea is to start sniffing each mug. The more cups of coffee you rule out, the better your chances of determining which two contain tea. Similarly, a process of eliminating non-cancer gene markers helps characterize a PSA that indicates likelihood of cancer.

How did the authors find the genetic markers they could safely rule out? They began with a “… genome wide analyses of PSA levels ≤10 ng ml^?1 in men never diagnosed with prostate cancer.” In total, this involved 95,768 men without PCa. The team identified 128 variants, and correlated them by ancestry categories: European, East Asian, Hispanic/Latino, and African. Doing so gained further clarity for individualized genetic PSA adjustment. Thus, they developed a polygenic score (PGS) enabling them to adjust a standard PSA test result (PGS-adjusted PSA) for each individual’s blood test. A June 16, 2023 Renal & Urology News story reported:

The researchers identified 128 genome-wide significant associations … In men of European ancestry, using PGS-adjusted PSA would avert up to 31% of negative prostate biopsies but also result in 12% fewer biopsies among patients with prostate cancer, mainly tumors with a Gleason score <7. Compared with unadjusted PSA, genetically adjusted PSA was more predictive of aggressive prostate cancer …^[ii]

This is promising news. If each man’s unique genetic profile score clarifies his PSA test in order to lower the risk of unnecessary biopsy, it would maintain the value of broad PSA screening. It’s a fact that early detection saves lives. Just as important, diagnosing an individual’s PCa when it is small and low-risk may qualify him for a focal therapy that destroys the tumor with minimal-to-no sexual or urinary side effects.

For such patients, the Sperling Prostate Center offers a choice of three MRI-guided outpatient focal treatments: Focal Laser Ablation, TULSA-PRO, and Exablate (MRI-guided Focused Ultrasound). This allows Dr. Sperling to discuss with patients which is the optimum match for his cancer and his lifestyle. Contact our Center for more information.

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] Kachuri L, Hoffmann TJ, Jiang Y, Berndt SI et al. Genetically adjusted PSA levels for prostate cancer screening. Nat Med. 2023 Jun;29(6):1412-1423.
[ii] Renal & Urology News. “Genetically Adjusted PSA Levels Improve Prediction of Prostate Cancer.” June 16, 2023. https://www.renalandurologynews.com/home/news/urology/prostate-cancer/genetically-adjusted-psa-levels-improve-prediction-of-prostate-cancer/