Swedish Biomarker Test STHLM3 Identifies Aggressive Form of Prostate Cancer

Henrik Grönberg, MD, PhD

Critics of prostate-specific antigen (PSA) screening point out that it has a high false-positive rate that can result in unnecessary prostate biopsies, overdiagnosis of low-risk prostate cancers, and overtreatment. Therefore, identifying a more accurate way of testing for prostate cancer could save resources and reduce patient suffering.

That new method may be on the way. A test called the Stockholm 3 (STHLM3) has been shown to detect aggressive cancer earlier, reduce the number of false positives, and decrease the number of unnecessary biopsies. Results were published in Lancet Oncology and involved 58,818 men from the Swedish Population Register, which is managed by the Swedish Tax Agency.

The PSA test “can’t distinguish between aggressive and benign cancer,” said lead investigator Henrik Grönberg, MD, PhD, in a statement. Between 2012 and 2014, Grönberg, professor of Cancer Epidemiology at Karolinska Institutet, and colleagues conducted a prospective, population-based, paired, screen-positive diagnostic study of men aged 50 to 69 years without prostate cancer.

The test, developed by researchers at Karolinska Institutet and in collaboration with Thermo Fisher Scientific, consists of a combination of plasma protein biomarkers (PSA, free PSA, intact PSA, hK2, MSMB, and MIC1), 232 genetic polymorphisms, and clinical variables, including age, family history, and previous prostate biopsies.

In the study, all participants were tested using the STHLM3 test and PSA test. The results were compared side-by-side. The STHLM3 test performed significantly better than the PSA test for detection of cancers in men with a Gleason score of at least 7 (P <.0001). The area under the curve was 0.56 (95% CI, 0.55-0.60) with PSA alone and 0.74 (95% CI, 0.72-0.75) with the STHLM3 test. The researchers said that use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI, 24-39) and could avoid 44% of benign biopsies (95% CI, 35-54). In addition, the STHLM3 test found aggressive cancers in men with low PSA values (1-3 ng/ml)—cancers that are currently undetected.

The primary endpoints of the study were the number of detected high-risk prostate cancers (sensitivity) and the number of performed prostate biopsies (specificity). Secondary endpoints were to decrease the number of low risk prostate cancers diagnosed, to investigate the health related quality of life and knowledge of prostate cancer testing, to assess the health economic consequences of implementing prostate cancer screening, to improve the quality and effectiveness of prostate cancer diagnosis in routine health care, and to assess the overall long-term mortality of prostate cancer.

To date, no diagnostic test based upon the STHLM3 model has been approved for use by the FDA or other regulatory agencies outside the United States. The authors note that STHLM3 is the first large-scale diagnostic study in prostate cancer where biopsy decision is prospectively based on the results from the predefined STHLM3 model.

“The study authors put this all in perspective by pointing out that a 30% reduction in prostate biopsies would translate to 300,000 fewer procedures annually in the United States,” said Joseph Bernardo, president of Thermo Fisher’s clinical next-generation sequencing and oncology business. “So in addition to improving patient experience and outcomes, there is also the potential for significant healthcare cost savings.”

The authors wrote that a full economic assessment would be published in a separate report.

The authors concluded that the STHLM3 model could be used as an aid to identify high-risk prostate cancers in men aged 50 to 69 years with a PSA concentration of at least 1 ng/mL. They said the test can reduce the number of prostate biopsies and the detection of clinically insignificant disease, while maintaining the sensitivity to clinically significant prostate cancer.

“The STHLM3 test will be available in Sweden in March 2016 and we will now start validating it in other countries and ethnic groups,” said Grönberg.

Grönberg H, Adolfsson J, Aly M, et al. Prostate cancer screening in men aged 50-69 years (STHLM3): a prospective population-based diagnostic study. [published online November 9, 2015] Lancet Oncol. doi:10.1016/S1470-2045(15)00361-7.