Breaking News!! Brits present game-changing spit test to help determine when, and if, to start screening for prostate cancer
Updated with comments from William Catalona, MD, a pioneer in PSA and PRS testing...
By Howard Wolinsky
British researchers have presented at the American Society for Clinical Oncology meeting in Chicago results on a new genetic “spit test” to help determine when, and if, to start screening for prostate cancer.
The new test, developed at the Institute of Cancer Research, London (ICR) and the Royal Marsden NHS Foundation Trust, appears to be a better alternative to PSA (prostate-specific antigen) blood tests. It’s not yet on sale.
Image: DNA sequence. Credit: The Institute of Cancer Research, London
For the men with the highest genetic risk, the test falsely identified fewer patients with prostate cancer than the PSA test, picked up people with cancer who would have been missed by the PSA test alone, and picked up a higher proportion of the aggressive cancers than the PSA test. The test also accurately identified men with prostate cancer that was missed by an MRI scan.
Could the PRS test give PSAs, the standard test used since the late 1990s to detect cancers, a run for the money? It sounds like this could be it—though we keep hearing about game-changing screening tests.
“With this test, it could be possible to turn the tide on prostate cancer,” said Rosalind Eeles, a professor of oncogenetics at the ICR. “We have shown that a simple, cheap spit test to identify men at higher risk due to their genetic makeup is an effective tool to catch the cancer early.
I asked William Catalona, MD, a pioneer in PSA and genetic testing, about the value of the new test: “Short answer: This approach has merit and I believe ultimately will become an adjunct to PSA testing.”
He added: “This topic is controversial, and there likely will be pushback on this presentation, because some previous studies involving fewer prostate cancer-risk SNPs (single nucleotide polymorphisms) have concluded prematurely that prostate cancer polygenic risk scores (PRS) can distinguish between prostate cancer and no prostate cancer but cannot distinguish between aggressive and indolent prostate cancer. In truth, as shown in our studies and others, there are some prostate cancer risk SNPs associated with more aggressive prostate cancer.”
(Prof. Rosalind Eeles)
“Our study shows that the theory does work in practice – we can identify men at risk of aggressive cancers who need further tests, and spare the men who are at lower risk from unnecessary treatments.”
Researchers developed the spit test after studying the DNA of hundreds of thousands of men. It reads genetic signals in the saliva linked to prostate cancer.
The test found fewer false positives than PSA and detected men with cancer in whom PSA would have been missed, and picked up a higher proportion of the aggressive cancers than the PSA test, the ICR said.
The test also accurately identified men with prostate cancer that had been missed by an MRI scan.
Eeles said the test found fewer false positives than PSA and detected men with cancer whose PSA would have been missed, and picked up a higher proportion of aggressive cancers than the PSA test.
The test also accurately identified men with prostate cancer that had been missed by an MRI scan.
PSAs can miss clinically significant cancers, on the one hand, and also cause men to undergo needless treatment or unnecessary biopsies and MRI scans..
The test calculates the polygenic risk score (PRS) based on 130 genetic variations in DNA code that are linked to prostate cancer.
The study calculated the polygenic risk score (PRS) of 6,142 European men recruited from their GP surgeries, aged 55-69 – an age at which the risk of prostate cancer is boosted. The score is based on 130 genetic variations in the DNA code that are linked to prostate cancer, and it was developed by studying the DNA of hundreds of thousands of men. Since the study began, an international research team has identified more risk variants for men of Asian and African ancestry, and the ICR team will be testing a saliva test for this population.
The men with the highest 10% of risk scores – who have inherited many of these variants and are most at risk of developing the disease – were invited to undergo further screening.
Following an MRI and prostate biopsy, 187 (40%) of the 558 men with a high PRS were diagnosed with prostate cancer. This compares with the PSA test, in which 25% of men with a high PSA level will actually have prostate cancer.
(See my articles below on PRS: https://www.medscape.com/viewarticle/996114 and
Know the score on a new type of DNA testing: Polygenic risk scores (PRS)
By Howard Wolinsky Genetic testing is a three-legged stool. Most of us have only heard of two of the legs (germline and somatic), but we (and our urologists and GPs) have heard little to nothing about the third leg--polygenic risk scores (PRS), which are just becoming available.
Brian Helfand, MD, PhD, chief of urology at NorthShore University HealthSytems outside Chicago and expert on DNA testing, said of the new study:
“The study design is very impressive. The genetic test is really designed to identify high-risk individuals of developing cancer. Men with high genetic risk are not only more susceptible to the disease but they develop it at early ages.
“In my opinion, the test is designed to help identify when to start prostate cancer screening and modify the frequency of screening. It also has utility in stratifying men with elevated PSA values who are considering biopsies. This study demonstrates that the genetic test can be used in a more efficacious way than PSA to find cancers and potentially more aggressive diseases. The only issue with this study is that it ignores men with lower genetic scores. Many of these men are at risk of prostate cancer and aggressive tumors.”
Catalona warned: “A concerning issue for me is that PRS testing with earlier PRS SNP panels and without adjustment for PSA SNPs have recently been released commercially by a few companies. These tests should be inexpensive – shouldn’t cost more that ~$250. And they can be done simply by having patients spit into a saliva tube and dropping the tube in the mail. Less accurate commercial tests could be aggressively marketed to select patients for PSA screening or active surveillance and yield inferior results that could adversely affect patient outcomes.”
Eeles said: “Our next step will be for us to test the genetic markers we have identified that are associated with a risk of prostate cancer in diverse populations, to ensure this test can benefit all men. We are currently comparing the saliva test to other potential screening options, as part of the TRANSFORM trial, to assess the most cost-effective and accurate way to screen men for prostate cancer.”
The researchers are presenting findings from the study at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. The research was funded by the European Research Council, the Bob Willis Fund, Cancer Research UK, The Peacock Trust, and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden and The Institute of Cancer Research (ICR).
Total eclipse of the heart and prostate: ASPI seminar on June 22
By Howard Wolinsky
Kevin T. McVary, MD, FACS, is a professor of urology and director of the Center of Male Health Stritch School of Medicine, Stritch School of Medicine, Loyola University Medical Center in Maywood, Illinois, outside Chicago.
McVary is a rare researcher on the heart and prostate gland and related issues.
He will be speaking at an Active Surveillance Patients webinar on Saturday June 22, 2024 at noon Eastern. The program is entitled “Matters of the Heart—and the Prostate.”
Register here: https://zoom.us/meeting/register/tJ0rdeGtrDIpEtynJ_U3A1rpWYkiCOHRMagt
I asked Northwestern University's William Catalona, MD, the developer of PSA testing and a genetic research pioneer, what he thought of this new development.
Here's his response:
Short answer: This approach has merit and I believe ultimately will become an adjunct to PSA testing.
This topic is controversial, and there likely will be pushback on this presentation, because some previous studies involving fewer prostate cancer-risk SNPs (single nucleotide polymorphisms) have concluded prematurely that prostate cancer polygenic risk scores (PRS) can distinguish between prostate cancer and no prostate cancer but cannot distinguish between aggressive and indolent prostate cancer. In truth, as shown in our studies and others, there are some prostate cancer risk SNPs associated with more aggressive prostate cancer.
Rosalind Eeles and Zsofia Kote-Jarai in the UK have led the way in their PRACTICAL Consortium by genotyping hundreds of thousands of men to discover many of the first 269 prostate cancer risk SNPs (I was a collaborator with deCODE Genetics that discovered the first risk SNP on chromosome 8q24). In these so-called GWAS (genome-wide association studies) studies, 40-50% of the aggressive cases have PRS scores in the top two PRS deciles, and few aggressive cases are in the bottom deciles. So, there’s no doubt that patients with aggressive tumors tend to have higher PRS scores. In fact, patients whose PRS are in the very highest deciles have a risk comparable to BRCA2 pathogenic mutation carriers.
Recent studies led by the USC group , including Christopher Haiman, David Conti, and Burcu Darst involving nearly 1 million US veterans have expanded the number of prostate cancer risk SNPs to 451, which has improved the discrimination for aggressive disease. Our prostate SPORE project, led by John Witte (Stanford) and me was the first to demonstrate that the 269 PRS was significantly associated with conversion from active surveillance to treatment.
In that study, we found that SNPs for a man’s genetically-regulated PSA secretion levels also are significantly associated with conversion from active surveillance. John Witte’s research group has a large NIH grant to further study PSA SNPs. This is important because PSA testing is confounded because PSA levels are increased not only in men who are genetically high PSA secreters, but also in men with BPH and/or prostatitis and men with prostate cancer. This confounding reduces the clinical specificity of PSA testing. However, in recent as-yet unpublished studies, we have found that adjusting the 451 PRS for PSA secretion SNPs is significantly associated with grade reclassification in men on AS (in the Canary PASS active surveillance consortium who were genotyped in our SPORE study).
There are also SNPs predicting the development of BPH. We are currently investigating whether adjusting the 451 PRS for the BPH SNPs will further improve the accuracy of PRS testing for prostate cancer aggressiveness. These studies are a major component of the NCI Program Project proposal that our PCASP (Prostate Cancer Active Surveillance Project) group is now negotiating with the NCI staff for permission to submit.
A concerning issue for me is that PRS testing with earlier PRS SNP panels and without adjustment for PSA SNPs have recently been released commercially by a few companies. These tests should be inexpensive – shouldn’t cost more that ~$250. And they can be done simply by having patients spit into a saliva tube and dropping the tube in the mail. Less accurate commercial tests could be aggressively marketed to select patients for PSA screening or active surveillance and yield inferior results that could adversely affect patient outcomes.
Best regards,
Bill
Remind me again why is it helpful to avoid “diagnosis leading to AS.” With my family history of PC, I’m very glad that I’m going to be getting PSA 2-3 times a year rather than once, as well as periodic MRIs and biopsies.