Polygenic Risk Score - the “new and improved” PSA screening result

This study led to an even larger trial (TRANSFORM) just started this spring in the UK. It will involve hundreds of thousands of men.

Genetic testing is the future and is becoming mainstream.

Thank you for sharing that. Is the genetic testing primarily for screening, to test your risk of prostate cancer, or could it also replace PSA tests for monitoring progression in someone who's already known to have prostate cancer?

I'm guessing it's just the first one, but I really know nothing about it.

Actually the blood test couldnt be any simpler. Have to collect a separate "spit" sample seems unnecessary. You would think they could just use your blood. Accuracy is everything.

Actually, PRS is not looking all that promising, unfortunately, at least according to this study:

«PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death.»

In other words, PRS can show that you have a genetic risk of prostate cancer, but it doesn't help to differentiate whether it's dangerous or not as well as PSA does. Given that autopsies have shown over 50% of elderly men had prostate cancer at time of death (even if they didn't know it), that's not so useful.

Perhaps PRS would be helpful for routine screening for people who are afraid of needles and would otherwise avoid it (?)

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993880/

Not a good time to be squeamish about the blood draw for sure. I had LARP and decided to watch 4 surgeries by different surgeons, I found the entire procedure through a google search. I think training videos. these were all experts. My wife thought I was crazy but it gives you a perspective what your in for.

Yeah, I hear you. I'm a "hard poke" as the nurses and phlebotomists say, and during my months in hospital my arms were mostly black and blue from all the needles and IV catheters digging around looking for a vein. Sometimes they'd draw blood 4–5×/day.

This latest PRS news is that for men with the highest 10% of polygenic risk scores, 187 of them (40% of the total) were diagnosed with prostate cancer based on MRI and biopsy follow up.

It was also reported that this was a significantly higher percentage result than the 25% of PCa diagnosed men identified by PSA screening.

Interestingly, 147 (78%) of those PRS diagnosed men had a ‘normal’ PSA level. Apparently, PSA screening can also produce false negatives.

Even more importantly, the new saliva test identified a higher proportion of aggressive cancers – which are faster growing and more likely to spread – than the PSA test. Of the 187 cancers detected in the top 10% PRS risk group, 55% were aggressive cancers, compared with only 36% of those identified by a PSA test in a recent study.

As far as I can tell, this new saliva test is currently only being studied for screening, not ongoing PCa progression…but maybe later…who knows??

In any event, the UK’s NIHR and Prostate Cancer UK are spending £42m in a new prostate cancer screening trial (TRANSFORM) to test and compare various new PCa screening methods like MRI, PRS and others. It’s reported that hundreds of thousands of UK men will participate.

Hopefully, something better than PSA testing will be proven.

Easier and more-effective screening sounds promising. It's not directly relevant to any of us here (most of us have already been biopsied, so we know what kind of PCa we have), but if it keeps some people from needing to join the forum in the first place, that will be a good thing.

Understand your comment, but I’d imagine many on this site have family and friends who have yet to have a PCa screening test.

If/when our loved ones time comes, a more definitive, personalized, easy to obtain test will help reduce the “black hole” of uncertainty that attended our “higher, but normal PSA range” early days.

As a researcher myself, this kind of work pushes the envelope towards better medicine and…who knows…may lead to better personalized predictive metastatic risk analysis, regarding PCa progression, for those of us already diagnosed with low and intermediate risk disease.

Decipher genomic testing (post biopsy) has already demonstrated its value and maybe this technology can move the needle even further toward understanding progression risks, at lower cost, prebiopsy.

My MO at Mayo PHX agreed to do genetic testing on a germline and somatic tissue samples. No I have a complete diagnostic data set, i.e. PSAs for many months, an initial MRI scan, biopsy, PSMA PET/CT scan, a high resolution MRI scan and soon genetics. Data is money in the bank. Genetics can identify those mutations causing PCa for which immunotherapy may be especially effective.