The Stockholm3 (A3P Biomedical) multiparametic blood test has shown accuracy in assessing the risk of prostate cancer, exceeding that of the standard prostate-specific antigen (PSA)-based test, in Swedish patients.
“The Stockholm3 outperformed the PSA test overall and in every subcohort, with an impressive reduction of unnecessary biopsies of 40% to 50%, while maintaining relative sensitivity,” first author Scott E. Eggener, MD, said in presenting the findings at the ASCO Genitourinary Cancers Symposium. The test “has attractive characteristics in a diverse cohort, including within various racial and ethnic subgroups,” added Dr. Eggener, professor of surgery and radiology at the University of Chicago.
While the PSA test, the standard-of-care in prostate cancer risk assessment, reduces mortality, the test is known to have a risk for false positive results, leading to unnecessary prostate biopsies, as well as overdiagnosis of low-risk prostate cancers, Dr. Eggener explained in his talk.
Randomized trials do show “fewer men die from prostate cancer with screening [with PSA testing], however, the likelihood of unnecessarily finding out about a cancer, undergoing treatment, and exposure to potential treatment-related side effects is significantly higher,” Dr. Eggener said in a interview.
The Stockholm3 clinical diagnostic prostate cancer test, which has been used in Sweden and Norway since 2017, was validated in a sample of nearly 60,000 men in the STHLM3 study (doi: 10.1016/S1470-2045[15]00361-7), which was published in The Lancet Oncology in December 2015. That study showed significant improvement over PSA alone detection of prostate cancers with a Gleason score of at least 7 (P < .0001), Dr. Eggener explained.
The test combines five plasma protein markers, including total and free PSA, PSP94, GDF-15 and KLK2, along with 101 genetic markers and clinical patient data, including age, previous biopsy results and family history.
Because the Stockholm3 test was validated in a Swedish population cohort, evidence on the accuracy of the test in other racial and ethnic populations is lacking, the authors noted in the abstract.
Study Methods and Results
To further investigate, Dr. Eggener and his colleagues conducted the prospective SEPTA trial, involving 2,129 men with no known prostate cancer but clinical indications for prostate biopsy, who were referred for prostate biopsy at 17 North American sites between 2019 and 2023.
Among the men, 24% were self-identified as African American/Black; 46% were White/Caucasian; 14% were Hispanic/Latina; and 16% were Asian. The men’s median age was 63; their median PSA value was 6.1 ng/mL, according to the abstract.
Of the patients, 16% received magnetic resonance imaging (MRI)-targeted biopsies and 20% had prior benign biopsies, the abstract notes.
Biopsy results showed that clinically significant prostate cancer, defined as International Society of Urological Pathology (ISUP) Gleason Grade group ≥ 2, was detected in 29% of patients, with 14% having ISUP 1 cancer and 57% of cases having been benign, according to the abstract.
Overall detection rates of grade 2 or higher were 37% for African American/Black, 28% for White/Caucasian, 29% for Hispanic/Latino, and 21% Asian.
In terms of sensitivity of the two tests, the Stockholm3 (cut-point of ≥ 15) was noninferior compared with the traditional PSA cut-point of ≥ 4 ng/mL (relative sensitivity 0.95).
Results were consistent across ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70), the abstract authors reported.
Compared with the use of the PSA test’s cut-point of ≥ 4 ng/mL, the use of Stockholm3’s cut-point of ≥ 15 or higher would have reduced unnecessary biopsies by 45% overall, including by 46% among Asian and Black/African American patients, by 53% in Hispanic patients and 42% in White patients, according to the abstract.
Overall, “utilization of Stockholm3 improves the net benefit:harm ratio of PSA screening by identifying nearly all men with Gleason Grade 2 or higher, while minimizing the number of men undergoing biopsy who show no cancer or an indolent cancer (Gleason Grade 1),” Dr. Eggener said in an interview.