- In a recent study, the Stockholm3 risk assessment tool outperformed PSA alone in detecting clinically significant prostate cancer, identifying 90% of cases compared with 74% detected by traditional PSA screening.
- Specificity was similar across the two approaches, indicating that Stockholm3 improved cancer detection without substantially increasing false-positive rates.
- The multivariable risk tool combines PSA levels with genetic markers, blood-based proteins, and clinical risk factors to provide a more comprehensive assessment of an individual’s prostate cancer risk.
- The findings suggest that risk-based screening strategies could improve the identification of aggressive prostate cancers while helping to limit unnecessary biopsies and follow-up procedures. However, longer-term studies are needed to evaluate the impact on patient outcomes.
At the same time, PSA screening can miss some aggressive cancers that require treatment. As such, researchers continue to investigate whether combining PSA with additional risk factors could improve the accuracy of screening.
Now, a new study suggests that a multivariable screening test, known as Stockholm3, may identify significantly more clinically important prostate cancers than the traditional PSA blood test alone.
Published in the Annals of Internal Medicine, alongside a patient summary, the findings note that the tool detected 90% of clinically significant prostate cancers, compared with 74% detected through PSA screening alone, while maintaining a similar ability to avoid false-positive results.
Stockholm3 is a multivariable risk assessment tool that combines PSA measurements with genetic markers, blood proteins, and clinical information to generate an individual’s risk score for prostate cancer.
The tool aims to better identify men who are most likely to have clinically significant disease, classified as cancers that are more likely to grow, spread, or require treatment, while reducing unnecessary follow-up procedures.
The researchers, from Karolinska Institutet and collaborating institutions, conducted a secondary analysis of the STHLM3-MRI randomized screening trial.
The large analysis included more than 12,600 males ages 50 to 74 years who underwent both PSA testing and the Stockholm3 assessment.
“The most important finding is that Stockholm3 detected substantially more clinically significant prostate cancers than PSA at comparable false-positive rates.”
“In our study, all men were followed for two years through Sweden’s national cancer registry after providing a blood sample. Stockholm3 identified 90% (400/443) of clinically significant cancers diagnosed during follow-up, compared with 74% (327/443) for PSA ≥3 ng/mL,” Palsdottir said.
“In other words, for the same number of men referred for further assessment, Stockholm3 missed only 10% of clinically significant cancers, whereas PSA ≥3 ng/mL missed 26%.”
— Thorgerdur Palsdottir, PhD
“We also evaluated the commonly used U.S. threshold of PSA ≥4 ng/mL. At this threshold, PSA detected only 52% (231/443) of clinically significant cancers, meaning that nearly half of these cancers were not identified at the initial screening test,” he said.
The analysis found that Stockholm3 was substantially more sensitive than PSA testing alone for identifying clinically significant prostate cancer.
“Stockholm3 is designed as a blood-based screening test that combines PSA with four additional protein biomarkers, clinical information such as age and family history, and a genetic risk score,” Palsdottir explained to MNT.
“These factors are integrated into a single risk prediction model that estimates an individual’s likelihood of having clinically significant prostate cancer at biopsy,” he said.
“Because Stockholm3 uses a standard blood sample, implementation is straightforward for healthcare systems already offering PSA testing.”
— Thorgerdur Palsdottir, PhD
90% vs. 74% significant cases
According to the results, Stockholm3 detected 90% of clinically significant prostate cancers, while PSA testing detected 74% of clinically significant cases. The two approaches showed similar specificity, suggesting they were equally effective at correctly identifying men without significant cancer.
Notably, the Stockholm3 approach also resulted in fewer missed cancers while producing a comparable number of unnecessary biopsies.
Palsdottir was not surprised by the magnitude of the difference in detection rates, noting “Studies using Stockholm3 have shown that a substantial proportion of clinically significant prostate cancers occur in men with PSA levels below commonly used thresholds (PSA ≥4 ng/mL in the US).”
He said the study results demonstrate that Stockholm3 can “identify cancers in men with low PSA levels by incorporating additional biological and clinical information.”
“What was particularly encouraging was that the performance remained strong during two years of follow-up. This provides additional confidence that men classified as low risk by Stockholm3 can safely return for repeat screening after an appropriate interval.”
— Thorgerdur Palsdottir, PhD
Fewer biopsies and MRIs
These findings suggest that the test may offer a better balance between detecting aggressive cancers and limiting unnecessary investigations.
“The results support using Stockholm3 as the initial screening test before MRI and biopsy. Men with a positive Stockholm3 result can be referred for MRI, which can then help determine whether a biopsy is warranted,” Palsdottir added.
“This approach improves the diagnostic pathway. By combining risk-based screening with MRI before biopsy, it is possible to reduce unnecessary biopsies, decrease the detection of clinically insignificant cancers, and minimize biopsy-related complications while maintaining a high detection rate for clinically significant disease.”
— Thorgerdur Palsdottir, PhD
The results add to growing evidence that risk-adapted screening approaches may improve prostate cancer detection compared with relying on PSA levels alone.
“Beyond this study, Stockholm3 has demonstrated similar diagnostic discriminations across diverse populations,” Palsdottir said.
He said results from the multiethnic North American cohorts (SEPTA trial) show that the Stockholm3 test delivers the same high level of diagnostic accuracy and consistency, regardless of a patient’s race or ethnicity.
“To date, apart from PSA, this represents the largest evaluation of a prostate cancer biomarker in minority populations. These findings support the generalizability and equity of the Stockholm3 algorithm across diverse populations and healthcare systems,” he pointed out.
“Compared to PSA, Stockholm3 reduced unnecessary biopsies by 45% while maintaining non-inferior sensitivity for detecting clinically significant prostate cancer. Importantly, diagnostic performance was comparable across racial and ethnic groups, supporting the generalizability and equity of the Stockholm3 algorithm across populations.”
— Thorgerdur Palsdottir, PhD
By combining PSA results with genetic, biochemical, and clinical information, multivariable tools such as Stockholm3 may improve the accuracy of prostate cancer screening and help clinicians make more informed decisions about which patients should undergo further testing, such as MRI scans or biopsies.
The researchers caution that longer-term follow-up is necessary before the test can be recommended for widespread use in national screening programs. Future studies will need to determine whether the improved detection rates ultimately translate into lower rates of advanced disease and prostate cancer-related deaths.
Palsdottir noted that PSA screening’s main limitation is that it cannot give an accurate assessment of prostate cancer risk when used as the only screening tool.
“Some men with low PSA levels have aggressive cancers, while many men with elevated PSA do not have cancer at all,” he said.
“Our findings suggest that using Stockholm3 as the first-line screening test could improve the balance between benefits and harms by identifying more clinically significant cancers while maintaining similar false-positive rates. This may help patients and physicians make more informed decisions about further investigations such as MRI and biopsy.”
— Thorgerdur Palsdottir, PhD
