Multivariable blood test identifies aggressive prostate cancer more accurately than PSA
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Key takeaways:
- Stockholm3 blood test could have reduced unnecessary biopsies by almost half compared with PSA screening alone.
- Stockholm3 demonstrated superior specificity across all ethnic groups.
The Stockholm3 multivariable blood test demonstrated superior specificity of prostate cancer detection across a diverse population compared with PSA screening, according to findings presented at ASCO Genitourinary Cancers Symposium.
Results of Stockholm3 testing could have eliminated unnecessary biopsies of benign and low-grade tumors for 45% of men vs. data derived strictly from PSA.
“Although PSA is considered standard of care, this study confirmed previously shown associated harms of isolated PSA testing, suggesting better risk stratification is still needed in current clinical care,” Hari Thambiah Vigneswaran, MD, an attending urologist and researcher in translational epidemiology and prostate cancer at Karolinska Institutet, told Healio.
“Since the minority recruitment was so large in number, powered subanalysis was feasible and showed nearly identical results across all races and ethnicities,” he added. “Although detection of aggressive cancer was higher in Black and African American men and lower in Asian men in the cohort, the biomarker did not require different calibration for different races and ethnicities, making the results generalizable to current clinical practice.”
Background and methodology
Healio previously reported the American Cancer Society projected prostate cancer to have nearly 300,000 diagnoses in 2024, the second most of any cancer in the U.S.
However, screening for prostate cancer and determining next steps is a complicated and divisive issue.
“PSA was developed in the [1990s], and it’s a good test, but it’s not perfect because PSA can be elevated not just from prostate cancer, it can be elevated for benign reasons,” Vigneswaran said. “If you have an enlarged prostate, like [benign prostatic hyperplasia] or inflammation of the prostate, your PSA can be high. When you just look at PSA, it has a poor specificity. If it’s elevated a fairly invasive biopsy procedure can be done unnecessarily for a man who has a benign elevation of the PSA. [Additionally], you have to choose a certain threshold to use for PSA, keeping in mind that it’s got a poor specificity, you have to choose a threshold that’s somewhat high so you’re not doing all of these unnecessary biopsies, so you miss some aggressive cancers.”
Stockholm3 (A3P Biomedical) incorporates several variables such as five circulating plasma proteins, including PSA, germline genetic risk and clinical factors such as age and family history, Vigneswaran said.
The multivariable blood test has been “supported by extensive clinical evidence, including 90,000 men,” he added, but Vigneswaran and colleagues wanted to determine whether it could achieve noninferior sensitivity and superior specificity in a diverse population.
“When you evaluate new technology like a prostate cancer biomarker, it’s important to look at how to improve specificity in a high-risk group like Black men because a lot of markers are elevated risk when it comes to Black men,” Vigneswaran said.
Researchers conducted a prospective trial of men who received referrals for a prostate biopsy from 2019 to 2023 at 17 different North American locations. They also used bio-banked specimens from 2008 to 2020. Study participants had no previous prostate cancer diagnosis.
Results
The cohort comprised 912 enrolled men and 1,217 with bio-banked blood (median age, 63 years; 46% white; 24% Black; 16% Asian; 14% Hispanic).
Biopsies discovered clinically significant prostate cancer in 29% of patients, grade 1 disease in 14% and benign tissue in 57%, with variation in clinically significant prostate cancer detection across all four ethnic groups (37% in Black patients; 29% in Hispanic patients; 28% in white patients; 21% in Asian patients).
Reduction of unnecessary biopsies performed due to Stockholm3 would have ranged between 42% and 53% across all four ethnic groups.
“When we set it up, there was a secondary aim that we would need to recalibrate a model to fit different ethnicities and races, but in actuality we didn’t have to do that,” Vigneswaran said. “The area under the curve and performance was nearly exactly the same across all the races and ethnicities and overall.”
Stockholm3 had a specificity 2.91 times higher than PSA (95% CI, 2.63-3.22) and a sensitivity (0.95) nearly equal to PSA (95% CI, 0.92-0.99).
Next steps
Stockholm3 launches in the U.S. in the first quarter of 2024, Vigneswaran said, and it could be used to evaluate men with both low and high PSA scores.
“It can act as a rule-in test and a rule-out test,” he said. “You check PSA first, and at 1.5 [ng/ml] then, that’s your trigger to order a Stockholm3 test. If your Stockholm3 risk score is elevated, typically an MRI is performed. The advantage of Stockholm3....it allows you to identify those men who are at risk in the low PSA ranges, reduces some of the unnecessary diagnostic and treatment harms associated with the high PSAs, and can reduce MRI use.”
Vigneswaran believes Stockholm3 can reduce the issues surrounding prostate cancer screening and streamline it for the future.
“There’s been a problem for the last 20 years where we know prostate cancer kills men and we know it affects men, but we also know we can’t treat every prostate cancer,” he said. “That’s where the primary care doctors have had some hesitancy [because] they don't know what to do, and they need a little bit more guidance beyond the PSA,” he added. “The advantage with Stockholm3 is that you can use it in primary care settings where you see lower PSA values. You can find those men who are at risk and not just reduce the harms of prostate cancer but also improve detection by identifying those men who are at risk ... that would otherwise be missed with conventional PSA testing.”
For more information:
Hari Thambiah Vigneswaran, MD, can be reached at hari.vigneswaran@ki.se.
Perspective
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Samuel Haywood, MD
The discovery of PSA as a prostate cancer screening test revolutionized how we screen, detect and treat prostate cancer. However, as I say to my patients each day, it is not a perfect test. PSA can be elevated for many reasons besides cancer, and elevation is not specific for clinically significant or high-grade prostate cancer. Although patients with benign pathology on biopsy are glad they do not have cancer, many are frustrated that they had to undergo an invasive procedure.The Stockholm3 blood test highlighted here may help add to this space. By combining a unique set of blood markers and clinical data, the improved specificity of Stockholm3 compared with PSA can significantly reduce the number of prostate biopsies performed.
However, a good screening test should be generalizable across the population to maximize its use. The study highlighted here examined the test’s performance across several ethnic groups. Notably, the test demonstrated ability to decrease unnecessary biopsies across all groups studied, with reductions ranging from 42% to 53%. Although the researchers had actually planned to determine a correction factor to take race/ethnicity into account, the test itself was able to perform similar across all groups on its own.
Given the significant disparities in diagnosis and treatment of prostate cancer amongst race and ethnicity, there is value in this test that can perform similarly across the entire population. Further, the Stockholm3 test can be easily used by primary care physicians to help rule out some men with lower risk for prostate cancer. Given problematic access to specialist care for some men in underrepresented minority or rural demographics, the Stockholm3 test may extend the decision closer to the patient and reserve consultation for those at a demonstrated higher risk for prostate cancer.
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Vigneswaran HT, et al. Abstract 262. Presented at: ASCO Genitourinary Cancers Symposium; Jan. 25-27, 2024; San Francisco.
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