PSA and the prostate – going beyond this…
For decades, the Prostate-Specific Antigen (PSA) test has been the go-to screening
tool for prostate cancer… It’s simple, widely available, and relatively inexpensive.
But it’s also deeply flawed.
Elevated PSA levels can result from benign conditions like benign prostatic hyperplasia (BPH) or prostatitis, and not all prostate cancers cause a rise in PSA.
This lack of specificity has led to overdiagnosis, unnecessary biopsies, and overtreatment -especially of slow-growing tumours that might never pose a real threat.
So, what’s next?
Researchers and clinicians have been working to refine prostate cancer diagnostics, and they´ve found several biomarkers that are more accurate…
Find out below about PCA3, 4Kscore, and PHI (Prostate Health Index)…
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But I’m getting ahead of myself.
3 Alternative prostate cancer biomarkers to know about besides the PSA…
PCA3:
Prostate Cancer Antigen 3 (PCA3) is a non-coding RNA gene that’s overexpressed in more than 95% of prostate cancer tissues, but not in normal or benign prostate cells…
Unlike PSA, which is measured in blood, PCA3 is detected in urine samples collected after a digital rectal exam (DRE), which massages prostate cells into the urethra.
A high PCA3 score correlates with a greater likelihood of a positive cancer biopsy.
A pivotal study published in European Urology found that PCA3 had a higher specificity than PSA for detecting prostate cancer, especially in repeat biopsy settings…
Another meta-analysis, published in Prostate Cancer and Prostatic Diseases confirmed PCA3’s value in reducing unnecessary biopsies.
4Kscore:
The 4Kscore test combines four kallikrein protein markers in the blood:
* Total PSA
* Free PSA
* Intact PSA
* Human kallikrein 2 (hK2)
It also factors in age, DRE results, and prior biopsy history to calculate a personalised risk score for aggressive prostate cancer (Gleason score ≥7).
* It helps distinguish indolent tumours from clinically significant cancers.
* Reduces unnecessary biopsies by identifying men at low risk.
* Offers a numerical risk estimate (e.g., “You have a 12% chance of high-grade cancer”).
A landmark study, published in European Urology, showed that the 4Kscore could reduce biopsies by over 50% without missing high-grade cancers…
The test has also been validated in multiple cohorts across Europe and the US, including a 2015 study published in JAMA Oncology that confirmed its predictive accuracy.
Keep reading…
Men: This Comprehensive Natural Solution Helps Fortify Your Bladder!
It’s fascinating how the bladder works. As it fills up, the muscles relax. But when you go to the loo to pee, the muscles contract, and that pressure expels the urine through the urethra and out of your body.
It’s like when you want to empty your plastic water bottle out faster – you squeeze it and the stream coming out of the bottle neck strengthens.
But if you suffer from a swollen prostate, which pinches the urethra, making urination difficult, chances are also your bladder health could be affected…
You see, as you get older, your bladder muscles are already weaker, and your bladder walls are stiffer and more rigid as they lose their elasticity – making urinating more of a challenge.
Not only this, experts speculate that many men who suffer from a swollen prostate, also have an overactive bladder. When the urethra is squeezed by a swollen prostate, the bladder has to work harder to push the urine out. Over time, this can further weaken the bladder.
The result is a frequent and intense urge to urinate.
PHI:
The Prostate Health Index (PHI) is a mathematical formula that combines:
* Total PSA
* Free PSA
* [-2]proPSA (a PSA isoform more closely linked to cancer)
PHI provides a single score that correlates with the probability of prostate cancer, especially aggressive forms.
* It´s more accurate than PSA alone in detecting prostate cancer.
* It’s particularly effective in the gray zone (PSA levels between 2–10 ng/mL).
* Helps guide decisions about whether to proceed with biopsy.
A multicenter study published in The Journal of Urology found that PHI had significantly higher specificity than PSA, especially for detecting high-grade cancers.
The FDA approved PHI in 2012, and it’s now widely used in clinical practice.
Prostate Cancer and diagnostics – where is it heading…
The shift from PSA to multi-marker panels and risk-based algorithms reflects a broader trend in medicine: precision diagnostics…
Instead of a one-size-fits-all approach, these tools allow doctors to tailor decisions based on individual risk profiles, genetic markers, and tumour biology.
Other promising biomarkers and tools on the horizon include:
* SelectMDx: A urine-based test analysing mRNA levels of DLX1 and HOXC6.
* ExoDx Prostate IntelliScore: Uses exosomal RNA from urine to predict high-grade cancer.
* MRI fusion-guided biopsies: Combine imaging with targeted sampling for better accuracy.
With tools like PCA3, 4Kscore, and PHI, we’re entering an era where early detection doesn’t have to mean overreaction…
These biomarkers offer smarter screening, fewer unnecessary procedures, and better outcomes for men.
What hasn´t changed is that early detection is key, so schedule your prostate screening.
Reference:
https://www.europeanurology.com/article/S0302-2838%2808%2900778-1/pdf
https://www.europeanurology.com/article/S0302-2838%2824%2902379-0/ppt
https://stagezerolifesciences.com/wp-content/uploads/2025/05/prostatehealthindex-a_new_test_.pdf
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Most men make do and just hope that their BPH prostate concerns will pass them by. But it’s unlikely to get better unless you do something about it…
One out of two men has prostate trouble by the time they’re 50. And by the time you reach your 80s, your chances are at about 80% of having prostate trouble from benign prostatic hyperplasia (swollen prostate gland)!
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