Breaking: Home spit test may 'turn tide' on diagnosing prostate cancer, UK researchers say in NEJM
Updated test looking more broadly at ethnicities--an interview with the research leader
By Howard Wolinsky
A new prostate cancer screening test based on DNA extracted from saliva beating PSA blood tests and MRI screening in finding clinically significant prostate cancer, UK researchers eported in the BARCODE 1 study published in the New England Journal of Medicine.
(Polygenic risk score spit kit for early cancer detection.)
Ros Eeles, PhD, of the Institute of Cancer Research, London, who led the study, said: “With this genetic risk score test, it could be possible to turn the tide on prostate cancer diagnosis. We have shown that a relatively simple, inexpensive saliva DNA test to identify men of European heritage at higher risk due to their genetic markers is an effective tool to catch aggressive prostate cancer early.”
She added: “Building on decades of research into the genetic risk factors for prostate cancer, our study shows that the theory does work in practice – we can identify men at risk of life-threatening prostate cancer who need further tests and spare the men who are at lower risk from unnecessary prostate biopsies and treatments.”
(Sir Chris Hoy carrying the flag at closing ceremonies at Beijing Olympics.)
The test may provide a new way to detect PCa early in the face of a forecasted “tsunami” of prostate cancer cases worldwide. The UK at present is embroiled in a debate about PSA screening guidelines, promoted by some A-listers such as Sir Chris Hoy, an Olympic champion who was diagnosed with lethal prostate cancer in his 40s, and politicians, such as the current Health Secretary, while some urology experts feel widespread screening could lead to overdiagnosis of low-risk prostate cancer.
(Editor’s note. There is a prostate cancer awareness crusade going on in the UK on behalf of prostate cancer patients as some high-risk patients share their stories with the public. Some prostate cancer researchers may not have been prepared for their favorite disease to be thrust in the limelight as pols weigh in on what’s to be done. I wonder if prostate cancer screening controversies will ever be f… Read full story
BARCODE1 facts:
● The study involved 6,393 participants in this cancer prevention trial, with 745 invited forscreening based on their polygenic risk assessment,
● Prostate cancer detection in 187 patients, 55.1% had cancer classified as intermediate or higher risk (Gleason score ≥7), indicating the need for treatment, with 21.4% having cancer classified as unfavorable intermediate, high, or very high risk.
● Cancer would not have been detected in 74 (71.8%) of these participants according to the prostate cancer diagnostic pathway currently used in the United Kingdom (high PSA level and positive MRI results). In addition, 40 of the participants with cancer (21.4%) had disease classified as unfavorable intermediate risk or as high or very high risk according to National Comprehensive Cancer Network (NCCN) criteria.
Why are new tests needed?
The old stand-by PSA blood test is considered the best biomarker but it falsely indicates prostate cancer in men three out of four times and detects cancers which grow so slowly they are unlikely to ever be life-threatening – meaning that men may undergo unnecessary MRI scans, invasive prostate biopsies, and treatments.
Researchers from ICR and The Royal Marsden NHS Foundation Trust trialled their new DNA test which looks for genetic variants linked to prostate cancer – a genetic testing technique known as a polygenic risk score.
See my stories on PRS in Medscape and in The Active Surveillor.
BARCODE1 vs. PSA
BARCODE1 researchers used germline DNA extracted from saliva to derived polygenic risk scores (PRS) from 130 genetic variants known to be associated with an increased risk of prostate cancer development. Participants with PRS in the 90th percentile or higher were invited to undergo prostate cancer screening with multi-parametric MRI and transperineal biopsy, irrespective of PSA level.
Following an MRI and prostate biopsy, 187 (40%) of the 468 men aged 55-69 with a high PRS were diagnosed with prostate cancer. This compared with the PSA test, in which 25% of men with a high PSA level will actually have prostate cancer confirmed by biopsy.
Of these 187 men, 118 (63.1%) had a PSA level below 3.0ug/L, considered ‘normal’ and would usually indicate that no further screening is required.
The median age at diagnosis was 64 years (range, 57 to 73).
For the men with the highest genetic risk, the test falsely identified fewer people 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.
Researchers estimate that the spit test could identify up to 12,350 patients in the UK earlier, saving the National Health Service around £500 million a year.
(Prof. Ros Eeles—ICR)
UK researchers developing another new polygenic risk score covering men with African, Black Caribbean, and Asian ancestry
By Howard Wolinsky
The original polygenic risk score (PRS) (reported above) focused on white men of European Heritage.
Since the BARCODE 1 study began, researchers have identified more risk variants for men of Asian, African, and Black African-Caribbean ancestry.
The original saliva test from BARCODE1 could only be used for people of European ancestry as the genetic data weren’t available for men of Asian, African, or Black African-Caribbean ancestry, despite Black men being twice as likely to develop the disease.
Tpdated version of the test, called PRODICT, includes more than 400 genetic variants, common and rare, in the new test vs. 130 in the original test.
Used in diverse populations
The study aims to recruit 1,000 people with prostate glands—men, non-binary people and transwomen— from diverse ethnic groups, aged between 40 and 55 years.
“We’re now excited to be rolling out our updated test, PRODICT, to diverse populations –as Black men are twice as likely to develop prostate cancer – and younger groups, as those with a genetic predisposition are more likely to be diagnosed at younger ages,” said Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, and consultant in Clinical Oncology and Cancer Genetics at The Royal Marsden NHS Foundation Trust.
“We are also currently comparing the saliva test to other potential screening options, as part of the £42 million TRANSFORM trial, to assess the most cost-effective and accurate way to screen men for prostate cancer,” she said.
The Active Surveillor interviews Prof. Eeles
By Howard Wolinsky
The Active Surveillor last fall interviewed Prof. Eeles.
The Active Surveillor: In the UK, do patients have to initiate PSA testing? GPs are not allowed to bring it up?
Prof. Ros Eeles: The PSA test is available free to any man aged 50 and over who requests it.
Current government guidance advises that GPs should not proactively raise the issue of PSA testing with asymptomatic men as prostate cancer is common and may not cause symptoms or shorten someone’s life.
TAS: Do you have any idea what the uptake of PSA testing is in the UK? What is the false positive rate?
RE: In the UK, about 39% of men aged 45-69 years have undergone PSA testing in the past 10 years. https://www.bmj.com/content/362/bmj.k3581#ref-14
We know that the PSA test falsely indicates prostate cancer in men three out of four times and can detect cancers which grow so slowly they are unlikely to ever be life-threatening – meaning that men may undergo unnecessary MRI scans, invasive biopsies, and treatments.
TAS: Could PRODICT replace PSA testing?
RE: An ICR team is currently taking part in the £42 million TRANSFORM screening trial, which is aiming to find the best way to screen men for prostate cancer and double the number of lives saved.
Previous trials using PSA and biopsy to screen for prostate cancer have shown that it is possible to prevent between 8% and 20% of prostate cancer deaths depending on how regularly men are screened. TRANSFORM will test new approaches which have the potential to more than double this impact and reduce prostate cancer deaths by 40%. With more than 12,000 prostate cancer deaths in the UK alone this could mean thousands of men saved each year in the UK, and many thousands more worldwide.
TRANSFORM will allow us to rigorously test genetic markers on a large scale in men from diverse ancestries. This could give us the information we need to use genetic risk scores toidentify men at risk of aggressive cancer who will need regular tests, while sparing men at low-risk from having unnecessary biopsies and treatments.
[Note: Dr. Hashim U. Ahmed, chief investigator of TRANSFORM told me his timetable for the study:
—Stage 1 results will be available in 3 years
—Stage 2 (long-term outcomes) probably 10-15 years..
Wow, I’ll be close to 90 when those results come out, and hopefully alive and well and off surveillance.
Ahmed is Chair of Urology & Consultant Urological Surgeon | Imperial Urology.]
TAS: What is special about PRODICT compared to existing genetic tests?
RE: Our PRODICT test builds on our earlier saliva test to detect risk of prostate cancer – which we showed was more accurate for men with high genetic risk than the PSA test in men of European origin in London UK. Now, we’re excited to be able to roll out our test to diverse populations and younger groups, as we’ve expanded the number of gene variants the test looks for and also have included both common and rare variants in a single test.
We believe this test will be effective at identifying the men who have a high risk of prostate cancer due to their genetics. Since genetics is not the only factor at play when it comes to the disease, a combination of early diagnosis tools will be required.
What else is news in low-risk PCa-land?
By Howard Wolinsky
—Throw me a lifeline. Please take the survey on your opinions on transperineal vs.transrectal biopsy: [https://forms.gle/T5pRqU5ravLVQ8xk7] This poll is being run inconnection with a new British study that showed TP is better than TR in detecting prostate cancer:
Breaking: Transperineal biopsies find more prostate cancer, but also cause patients more pain and embarrassment
(Editor’s note: Please take a minute to respond to this survey on your experience with transperineal vs. transrectal biopsies: https://forms.gle/T5pRqU5ravLVQ8xk7 This is today’s topic, and I’ll run a follow-up.)
—Gotta’ have heart. Don’t miss the ASPI webinar on trying to fend off the greatest health threat we AS patients and most other prostate cancer patients face. It’s not prostate cancer. It’s heart disease. Dr. Darryl Leong, of McMaster U. (Go Marauders!), is a rare cardiologist who studies prostate cancer.
He is the speaker at Active Surveillance Patients International webinar from noon-1:30 p.m. Eastern on Saturday April 26. Register here: [https://zoom.us/meeting/register/xgT8w-i3Qp-iJkvOby0M9g]
—You’ve got guts. I have had my microbiome checked and reversed type-2 diabetes. How about you?
Researchers at University of California, San Diego are validating the gut microbiome—the community of germs in our gut that help keep us going— as a biomarker for prostate cancer aimed at men on Active Surveillance for low-risk prostate cancer. Participants get a free diet assessment/score, a microbiome report, and $25 gift card.
See if you’re eligible: [https://oncobiomix.studyenrollment.com/]
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Quite interesting. I went and got the SNPs list from the BARCODE1 study and asked my grad student (ChatGPT) to cross reference it to my 23&Me data.
Here's the bad news:
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Based on your BARCODE1 polygenic risk score, your estimated lifetime absolute risk of developing prostate cancer is approximately 99.96%.
This figure reflects the log-additive nature of risk in polygenic models and assumes no other modifying factors like protective environmental influences, lifestyle, or screening interventions. While this does not guarantee diagnosis, it places you in the highest possible genetic risk tier.
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Now when it comes to AIs, we must proceed cautiously. What this could be is akin to "Every man will die with PCa, some will die from it." Then there is the fact that I have been diagnosed at T1c. <sigh> More time added to my AS sentence 😉.
Posting for Mark Perloe, MD, moderator for the AnCan virtual support for low- to intermediate-risk PCa on polygenic risk scores (PRS).:
Mark Perloe
Fri, Apr 11, 10:02 AM (3 days ago)
to me
While the salivary PRS could be a major improvement over PSA in predicting prostate cancer risk I believe that it should be seen as a screening tool. I believe calling it diagnostic is a bit misleading.
Mark Perloe
Sherman Oaks, CA