UK study shows promise in using MRIs in initial screening for prostate cancer in low-level PSA patients. Could it work here?
MRIs finding more serious cancers, while sparing men from unnecessary biopsies
By Howard Wolinsky
Could there be a better way to screen men for prostate cancer—the most common solid cancer killer in men—using PSA combined with multi-parameter magnetic resonance imaging (MRI) while sparing men from biopsies?
Dr. Caroline Moore, a top MRI and prostate cancer researcher at University College London, and colleagues ask in their new study in BMJ Oncology: “How would MRI perform on its own if used in an age-defined—not PSA-defined—population setting?”
(Dr. Caroline Moore, University College London)
In fact, the MRI did pretty well in a small study, meriting further research.
Organized PSA screening, too, does a good job but at a cost.
The European Randomised Screening study for Prostate Cancer showed that organized screening can reduce prostate cancer mortality, compared with controls, by 20% at 16-year follow-up.
The cost? Overdiagnosis and overtreatment can be accompanied by urinary incontinence and erectile disorder. That’s why we go on Active Surveillance, close monitoring.
“Screening using prostate-specific antigen (PSA) as triage and transrectal biopsy as verification resulted in half of all detected cancers being low grade and unlikely to result in a prostate cancer death but was still associated with acceptance of radical treatment,” said Prof. Caroline Moore, a urologist at University College London and principal investigator of a new Re-IMAGINE study looking at MRIs.
The Re-IMAGINE study, published in BMJ Oncology, is the first to use MRI scans with PSA to assess the need for further UK’s standard National Health Service testing.
In the study, eight GP practices sent invitations for screening to 2,096 men. GPs only lent their names to the invites to assure reimbursement. The subjects were referred to hospital-based PSA screening and a 10-minute MRI.
In the end, 303 men aged 50-75 years underwent randomized screening MRI and PSA tests. Of those tested, 48 (16%) had a positive screening MRI that indicated there might be cancer despite only having a median PSA density result of 0.12 ng/ml.
[Divide your PSA level by the size of your prostate to calculate your PSA density. A high PSA density means that a relatively small volume of prostate tissue is making a lot of PSA, while a low PSA density means that a large volume of prostate tissue is making relatively little PSA. The target is a PSA density below 0.125.)
The current PSA level of 3 ng/ml is the typical cutoff when men get referred to a specialist in the UK. In the U.S., we may wait for a PSA of 3-4. before getting referred to a urological specialist.
(Check this FAQ on PSA from a UK urologist, Aidan Noon, https://www.topdoctors.co.uk/medical-articles/high-psa-reading-what-does-it-mean#)
In Re-Imagine, subjects with a positive MRI or a raised PSA density (≥0.12ng/mL2were recommended for standard National Health Service (NHS) prostate cancer assessment.
Those men with “low” PSAs in the study would not have been referred for further testing under standard practice. So MRIs were giving them a leg up on finding and managing their cancer while avoiding overdiagnosis and treatment with serious side effects.
Moore told the Guardian: “Our results give an early indication that MRI could offer a more reliable method of detecting potentially serious cancers early, with the added benefit that less than 1% of participants were ‘overdiagnosed’ with low-risk disease.”
This has special significance in the UK.
Prof. Mark Emberton, consultant urologist at UCLH, said: “The UK prostate cancer mortality rate is twice as high as in countries like the U.S. or Spain because our levels of testing are much lower than other countries.
“Given how treatable prostate cancer is when caught early, I’m confident that a national screening programme will reduce the UK’s prostate cancer mortality rate significantly. There is a lot of work to be done to get us to that point, but I believe this will be possible within the next five to 10 years.”
British guidelines do not recommend routine PSA screening. The U.S., in contrast, has some semblance of a national prostate screening program, though no more than about 50% of men—depending on the population in question--opt to undergo PSA screening.
There are efforts underway in the UK to change this situation and create a formal screening program, using “man vans” that go into communities in the communities and other innovations to test PSA. They hopefully will have more success than the U.S. did with similar efforts with testing at health fairs and the like in the early 2000s that contributed to overdiagnosis and overtreatment.
UK men over 50 can request a PSA test if they are experiencing symptoms that actually are uncommon in prostate cancer or are concerned about prostate cancer. Screening studies typically have used a PSA level of 3 ng/ml or above as a guide to performing additional tests, such as biopsies, to look for prostate cancer.
Study participants were invited in a letter from their general practitioners to undergo the testing regimen.
But Black men responded to the invitation for prostate cancer screening at one-fifth the rate as white men. That is a problem considering Black men's higher risk of developing aggressive prostate cancer and dying from it.
[Note: PHEN (Prostate Health Education Network) will address these issues in a webinar, the 19th Annual “African American Prostate Cancer Disparity Summit” 1-3:30 p.m. Eastern Sept. 6. 2023. Register here: https://tinyurl.com/mu7ebh4d Dr. Curtis Pettaway, a urologist at the University of Texas MD Anderson Cancer Center in Houston, will present recent data on active surveillance outcomes for Black men.]
Michael Leapman, MD, Associate Professor of Urology; Clinical Program Leader, Prostate & Urologic Cancers Program, Yale Cancer Center, told me the Re-Imagine study is “very thought-provoking. Although quite sensitive for detecting aggressive prostate cancer, we know that PSA is an imperfect marker.
“Using MRI as the screening tool is intriguing. It has always been assumed that we should use PSA as the initial screen because it is inexpensive, readily available, and non-invasive. From this framework, we generally discount the possibility of finding significant prostate cancer in patients with low PSA levels (e.g. less than 3). But here they show that ‘clinically significant’ (Gleason 3+4 or higher) was actually fairly prevalent in this low PSA group.
“I’m eager to learn more about this and see a larger study comparing MRI with PSA-first screening. It’s notable that there may be selection biases as only 22% of those invited responded. But as noted by the authors, (that) could reflect timing as the study coincided with the pandemic.
Dr. Todd Morgan, urology chief at the University of Michigan (Go Blue!), was impressed with the UK study.
“This is amazing data on multiple fronts. Incredibly interesting and compelling to see the rate of cancer detection for patients with a PSA under 3.”
But could this work in the U.S.?
Leapman said, “[This] could have implications for the U.S. but raises questions of cost-effectiveness as well as capacity. At present, most patients are not getting PSAs.”
Morgan added: “It is impossible to envision pulling this off in the U.S.—we simply don't have the resources to screen this broadly right now. This approach led to 20% of patients being recommended to undergo biopsy (wow), and it's likely that the vast majority of cancers would have been detected at a later date using a standard PSA threshold of 3 ng/ml, followed by MRI.
“That said, there were 2 patients in particular -- one with GG3 and one with GG5 disease -- who may have really benefited from this approach given their PSA levels below 3 ng/ml. Overall, this is a phenomenal study and huge credit should be given to the investigators and study participants. it shows that we need to keep innovating in this space to improve prostate cancer early detection.”
On the personal front, Moore’s earlier MRI research has had a large impact on my care. She co-authored an article that appeared in the New England Journal of Medicine in 2018, “Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy,” which showed that MRI is an alternative to standard transrectal ultrasonography–guided biopsy for prostate-cancer detection in men with a raised PSA level.
I shared the study with my urologist, who at point favored biopsies every other year, a schedule I rejected. I told him I felt low-risk patients like me would rebel against such frequent transrectal biopsies that exposed them to risk of infection, including deadly sepsis. He’s a laid-back dude, so it was a shock when he told me: “Tough.” He said these biopsies were his best tool.
But he changed, at least in my case,
He de-intensified my surveillance because my “cancer” is so stable. I haven’t had an MRI or biopsy since I joined his practice in 2016.
Not too late yet for these webinars:
(1) Dr. Stacy Loeb talks about lifestyle lifestyle program on Aug. 26—she’ll be there for a live Q&A
By Howard Wolinsky
Stacy Loeb, MD, of New York University Langone Health, has agreed to appear at a live Q&A after ASPI airs the latest segment of the Active Surveillance 101 video series,
The program focuses on the role of lifestyle factors for low-risk prostate cancer patients, including diet, exercise, and sleep.
Active Surveillance Patients International (ASPI) will host the free webinar from noon to 1:30 p.m. Eastern Saturday, Aug. 26. Register here: https://tinyurl.com/2attxbt4
Submit questions in advance to: contactus@aspatients.org
Registrants who can’t attend will get a link to the video.
In the AS 101 series, modeled after a basic college-level course, PCa patient Larry White and his well-informed wife Nancy question experts in the field on top-of-mind issues for patients on AS.
In this segment, urologist Loeb, who is studying to be board certified in lifestyle medicine, shares her research on the role of lifestyle—plant-based diet, exercise and sleep—plays in low-risk prostate cancer.
Loeb has followed a plant-based diet for the past three years and is on the cutting edge of research on lifestyle issues and prostate cancer.
For the AS 101 series to date, go to: https://aspatients.org/a-s-101/
Join trailblazing researcher Dr. Laurence Klotz in a webinar on focal therapy on Aug. 31
Dr. Laurence Klotz, of the University of Toronto, one of the fathers of active surveillance, also is a pioneer in focal therapy, methods to remove lesions without performing radical prostatectomies.
He will share his experienc in a free webinar at 8-9:30 p.m. August 31 entitled, "Is focal therapy right for your prostate cancer?" Register at https://attendee.gotowebinar.com/register/1495697985984134744
Send questions in advance to Joe Gallo at joeg@ancan.org,
You should leave the program with an understanding of whether you may be candidate—or not—for focal therapy. It’s not for everyone.
Focal therapy offers middle-ground therapy for men with localized prostate cancer. It uses ablation, or tissue destruction, to target the area that contains the index lesion. Men who have focal therapy will continue to be monitored after treatment.
This program is aimed at the newly diagnosed who are considering options and those who are considering leaving Active Surveillance.
If you can’t make it, register, and you’ll automatically get the link to the video link.
Laughing your prostate off in the Gleason PCa humor awards
By Howard Wolinsky
Submit your prostate jokes, cartoons, limericks, whatever—on DREs, PSAs, BPH, and prostatitis—to The Gleasons—Putting The Glee In Gleason Scores, the first prostate humor contest.
The contest, started by Jim-Bob Williams, a therapeutic humorist and Gleason 6 patient, and me, is open to doctors and patients alike.
Share your prostate humor at howard.wolinsky@gmail.com Jokes, limericks, poems, whatever floats your boat. We do play blue so ED and Viagra jokes are in play.
The deadline is Sept. 1. A distinguished panel will announce the winners later in September, Prostate Cancer Awareness Month.
(Sir Billy.)
In the professional division, AnCan Foundation has nominated Sir Billy Connolly’s over-the-top prostate exam bit: https://ancan.org/billy-connolly-prostate-examination/
Guaranteed that you’ll laugh your prostate—and ass—off.
Late breaking comments added from UMichigan's Todd Morgan.
Thanks to a sharp-eyed reader: Had a correction to median to PSA density 0.12. Those de.cimal leriods are a moving target