Is This the Best Screening Test for Prostate Cancer?
Findings from two recent studies could signal a paradigm shift in the way men are screened for prostate cancer.
In the ReIMAGINE study, a group of researchers from the United Kingdom found that half of men with apparently “safe” levels of prostate-specific antigen (PSA) below 3 ng/mL had clinically significant prostate cancers when multiparametric MRI was added to screening. The researchers, whose paper appeared last month in BMJ Oncology, also found that 1 in 6 screened men had a prostate lesion on MRI.
Meanwhile, a large Swedish population-based study, published last month in JAMA Network Open, showed that pre-biopsy MRIs combined with PSA testing after adoption of guidelines recommending MRIs led to a decrease in the proportion of men with negative biopsies (28% to 7%) and the number of Gleason score 6 cancers (24% to 6%), while the proportion of Gleason score 7 to 10 cancers rose from 49% to 86%
Researchers compared prostate MRI uptake rates in the Jönköping Region in southern Sweden over nine years — 2011 through 2018 before prostate MRIs were recommended nationally, and 2018-2020 when MRIs became commonly used.
David Robinson, MD, PhD, associate professor at Linköping University and leader of the Swedish study, told Medscape Medical News: “MRI is now standard for men before biopsy” in that country. In Sweden, which has a high rate of mortality from prostate cancer — about 50 deaths per 100,000 men vs 12 and 8 per 100,000 in the UK and United States, respectively — PSA testing is not routine. “Most men that are diagnosed with prostate cancer have no symptoms. They have asked for a PSA when they have visited their general practitioner,” Robinson said. “To take a PSA test is not encouraged but it is not discouraged either. It is up to each man to decide.”
Dr Caroline Moore
PSA screening is not common in the United Kingdom. Caroline Moore, MD, chair of urology at University College London and principal investigator on ReIMAGINE, said only 20% of UK men older than age 50 undergo PSAs tests because doctors in the UK are concerned about the sort of overdiagnosis and overtreatment of prostate cancer that has occurred in the United States since the mid-1990s, when PSA screening was adopted here.
The rate of PSA screening in the United States has declined with controversies over recommendations for screening, though they remain above European rates: 37% in 2019, down from 47% in 2005, according to a 2022 Veterans Administration study published last October in JAMA Oncology.
In the UK study, Moore’s hospital-based group asked general practitioners to send letters to 2096 men aged 50-75 years who had not been diagnosed with prostate cancer, inviting them to undergo prostate health checks combining screening with PSA and 10-minute prostate MRIs.
Of the 457 men who responded to the letters, 303 completed both screening tests. Older White men were more likely to respond, and Black men responded 20% less often.
Of the men who completed screening, 29 (9.6%) were diagnosed with clinically significant cancer and 3 were diagnosed with clinically insignificant cancer, the researchers reported.
Moore said the PSA and MRI-first approach spared men from biopsies as well as the downsides of active surveillance, which include close monitoring with urology visits and occasional MRIs or biopsies over many years. Biopsies are considered undesirable because of pain and the risk for sepsis and other infections associated with transrectal biopsies.
Dr William Catalona
But urologists in America were less convinced by the international data. William Catalona, MD, a urologist at Northwestern University in Chicago, who developed the PSA screening test in the 1990s, said he wasn’t surprised so many men in ReIMAGINE with low PSAs had advanced cancers. “Some of the most aggressive prostate cancers occur in men with a low PSA level — not new news,” he said.
Catalona also disagreed with the UK researchers’ emphasis on MRIs because the readings often are incorrect. A 2021 study in Prostate Cancer and Prostatic Diseases reported that multiparametric MRI had a false-negative rate of between 10% and 20%.
“MRI alone should not be considered more reliable than PSA. Rather, it should be considered complementary,” he said.
Michael Leapman, MD, MHS, associate professor of urology at the Yale Cancer Center, in New Haven, Connecticut, said the UK findings point to a role for MRI as a “triage tool” to help identify men with elevated PSAs who should have a prostate biopsy.
But he said the research to date doesn’t support the use of MRI as a stand-alone test for prostate cancer. “In my opinion, it would have to demonstrate some tangible benefit to patients other than finding a greater number of cancers, such as improvement in cancer control, lower burden from the disease overall, or cancer-specific survival,” he said.
Major US guidelines recommend including MRIs before biopsies. Leapman also pointed out that 2023 recommendations from the National Comprehensive Cancer Network state that MRI is “strongly recommended if available.” Yet fewer than half of US urologists use MRIs as a screening tool, he said.
“My sense is that MRI is not available everywhere. We have also seen that wait times are too long in some centers, leading physicians and patients to opt for biopsy — particularly in cases with higher suspicion,” he said.
The studies from Sweden and the UK “demonstrate the strides being made in reducing overdetection of low-grade prostate cancer will increase detection of clinically significant Gleason 3+4 or higher” tumors, Leapman said. “It is unclear whether such patients in whom their otherwise low-risk disease is recast as ‘intermediate risk’ meaningfully stand to benefit in the long term from this detection.”
Robinson reported no relevant financial conflicts of interest. The Swedish Cancer Society, the Swedish Research Council, Region Jönköping, Futurum, and Clinical Cancer Research Foundation in Jönköping supported the Swedish study. Members of the Re-IMAGINE study team disclosed research support from the United Kingdom’s National Institute of Health Research and various industry/other sources. The Medical Research Council and Cancer Research UK funded the Re-Imagine study.
Howard Wolinsky is a Chicago-based medical freelancer and a patient diagnosed with low-risk prostate cancer who has been on active surveillance since 2010.
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