Weeks after reporting results from their research demonstrating that magnetic resonance imaging (MRI) could reduce overdiagnosis and thereby improve prostate cancer screening, investigators at the Karolinska Institute in Sweden published a new study showing that the addition of a novel blood test, the Stockholm3 test, can reduce the number of MRIs performed by a third while further preventing the detection of minor, low-risk tumors.
“Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies,” write the investigators.
“We did a prospective, population-based, randomized, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50–74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomization.
“Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72–0·80) for Stockholm3 and 0·60 (0·54–0·65) for PSA.
“In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09–1·28], p<0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96–1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55–0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86–1·03).
“Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15–1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32–0·66]), and led to fewer biopsy procedures.
“Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group.
Test can inform risk stratification
“The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer.”
“Overall, our studies show that we have identified the tools needed to be able to carry out effective and safe screening for prostate cancer. After many years of debate and research, it feels fantastic to be able to present knowledge that can improve healthcare for men,” says Tobias Nordström, PhD, associate professor of urology at the department of clinical sciences, Danderyd Hospital at Karolinska Institute, who is responsible for the STHLM3MRI study.
Current screening methods–PSA (prostate-specific antigen) tests combined with traditional biopsies–result in unnecessary biopsies and the detection of numerous minor, low-risk tumors (overdiagnosis). Consequently, no country except Lithuania has chosen to introduce a nationwide prostate cancer screening program, as the benefits do not outweigh the disadvantages.
On July 9, 2021, results from the STHLM3MRI study were presented in The New England Journal of Medicine, indicating that overdiagnosis could be reduced by substituting traditional prostate biopsies with magnetic resonance imaging (MRI) and targeted biopsies. The new results discussed here show that the addition of the Stockholm3 test, which was developed by researchers at Karolinska Institute, can be an important complement. It is a blood test that uses an algorithm to analyze a combination of protein markers, genetic markers, and clinical data.
“The availability of MRI in healthcare will be a limiting factor. We now show that a novel blood test as adjunct to MRI can reduce the number of MRIs performed by a third. Compared with traditional screening, overdiagnosis is reduced by as much as 69 percent. At the same time, the number of biopsies is halved, while we can find just as many clinically significant tumors,” notes Martin Eklund, PhD, associate professor at the department of medical epidemiology and biostatistics, Karolinska Institute, with joint responsibility for the STHLM3MRI study.
STHLM3MRI is a randomized study that was conducted between 2018 and 2021 with 12,750 male participants from Stockholm County. The participants provided an initial blood sample for PSA analysis and analysis using the new Stockholm3 test. Men with test results showing elevated PSA levels were then randomly selected for traditional biopsies or MRI. In the MRI group, biopsies were conducted strictly on suspected tumors identified by MRI.
“Separate use of the Stockholm3 test and MRI has previously been shown to be cost-effective. We have now analyzed the cost-effectiveness when these tools are combined and will shortly report exciting results from that analysis,” says Nordström, who along with Eklund and Henrik Grönberg, MD, PhD, also at Karolinska, are partners of the company A3P Biomedical AB, which holds the development rights of the Stockholm3 test.