For researchers

Prostate-specific antigen (PSA) is widely used as an initial screening test for prostate cancer and is largely credited with the reduction in prostate cancer mortality reported during the past two decades. The European Randomized Study of Screening for Prostate Cancer (ERSPC) showed a 21% reduction in prostate cancer mortality with structured PSA screening after13 years. However, the poor specificity of PSA translates into many unnecessary prostate biopsies and over diagnosis of low-risk prostate cancers. Subsequently, no governmental body has recommended structured PSA screening because of the potential harms of over diagnosis.

PSA is the only biomarker that has been assessed prospectively and in randomized controlled trials. Alternative plasma protein biomarkers other than PSA have been proposed to address these concerns. In addition to total PSA, the other plasma protein biomarkers used in the STHLM3 study were selected by a systematic scientific literature search during 2010 and two subsequent validation studies. Five additional biomarkers were selected based on their associations with the presence of prostate cancer with a Gleason score of at least 7. Urine-based markers were excluded because they would require a prostate massage, which makes them unsuitable to use in a population screening setting. On the basis of the literature and genetic assessment of previous studies, 254 SNPs were selected based on their association with prostate cancer risk.

Added value of the STHLM3 study

We showed that the STHLM3 model, a combination of plasma protein biomarkers, genetic polymorphisms, and clinical variables, can significantly improve prostate cancer screening specificity with the same sensitivity compared with the PSA testing using a cutoff of at least 3 ng/mL. The STHLM3 model can identify cancers with a Gleason score of at least 7 in men aged 50–69 years and identify clinically significant prostate cancers in the PSA concentration range of 1–3 ng/mL. The STHLM3 model also includes two novel biomarkers and genetics markers that have not been previously included in a prospective diagnostic study. Additionally, 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. Finally, STHLM3 is population based, thus minimizing selection bias and increasing the generalizability.

Implications of all the available evidence

Together with the results from the European Randomized Study of Prostate Cancer, the findings from the STHLM3 study indicate that prostate cancer mortality can be reduced but with substantially fewer biopsies and reduced over diagnosis.

Link to the article in The Lancet Oncology

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00361-7/abstract

The Article in The Lancet Oncology

Prostate cancer screening in men aged 50–69 years (STHLM3)- a prospective population-based diagnostic study

SUPPLEMENTARY Material – STHLM3- A prospective population-based diagnostic study for prostate cancer screening in men 50-69 years