Insights into prostate cancer biomarkers for better early detection

How, i.e. what approach and methods did you use to investigate the biomarkers? What specific challenges did you encounter?

When I (Dr. Charlie Hamm) began my residency at Greifswald University Hospital in 2020, I learned about the Study of Health in Pomerania (SHIP), a large population-based study in Mecklenburg-Western Pomerania with a long and structured follow-up. Inspired by this study design, I was able to secure funding for a prostate-related project and subsequently evaluate data from 2,651 men over a period of up to 20 years as part of a team.

The analysis incorporated data from physical examinations, blood values, and image information from whole-body MRI scans, with a particular focus on PSA levels and PSA density. It is easy to imagine that a project of this kind involves thousands of data points, which require repeated quality checks and plausibility checks to ensure that the final analysis is reliable. It should be emphasized, however, that this is a multidisciplinary project that was carried out through close cooperation between the SHIP consortium in Greifswald and our working group at Charité in Berlin.

What are the results of your analysis?

A low PSA level below 1.0 ng/mL between the ages of 45 and 70 was observed in around 56% of the study population and was associated with a very low 20-year risk of prostate cancer: only 3.3 percent. A PSA threshold of less than 1.5 ng/mL, which is currently also recommended in the German S3 guideline for prostate cancer, was found in as many as 75% of men and was also associated with a very low 20-year risk of 4.9 percent. Other markers examined, such as body mass index, blood lipid levels, or long-term blood sugar, showed no relevant association with the occurrence of prostate cancer.

What significance do your findings have for patients and future cancer screening? 

Our population-based data supports a paradigm shift in prostate cancer screening: away from the previous approach, in which elevated PSA levels were primarily used to identify men for further testing, toward an approach in which low PSA levels are specifically used to reliably identify men at very low risk. The very low long-term risk associated with a low PSA level in middle age suggests that extended screening intervals are acceptable for these men without overlooking a high number of prostate cancers. This could conserve resources, reduce unnecessary diagnostics and biopsies, and strengthen evidence-based, risk-adjusted early detection—in line with current European recommendations. The particular strength of our study lies in the long-term follow-up and analysis of an unselected general population. This enables particularly reliable findings for such targeted, risk-based early detection.

What specific steps are still necessary to make your findings useful for clinical application?

The study provides reliable data for the population of northern Germany. However, the incidence of prostate cancer varies considerably within Europe, meaning that the results cannot be readily transferred to other regions and population groups. Our findings must therefore be confirmed in further independent cohorts. In addition, prospective studies are needed to investigate how risk-adjusted screening can be integrated into organized early detection programs and whether it delivers the expected benefits. Finally, we would need to show that this approach is not only medically sound, but also cost-effective. The overarching goal is to integrate our adapted screening program into national early detection strategies in a structured manner.