Risk based prostate cancer testing
Description: Prostate cancer is the most common cancer and a leading cause of cancer death among men in Sweden. In 2013 over 10,000 men were diagnosed with prostate cancer and over 2,500 died of the disease. Prostate cancer incidence rates in Sweden are comparable to rates in countries that had an early introduction of PSA testing, while the prostate cancer mortality rate in Sweden is higher than in most other countries. Given the high prevalence of prostate cancer and limited opportunities for primary prevention, a good screening test could reduce health burden and mortality.
The Göteborg arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown that PSA based screening can decrease prostate-specific mortality by 44%. However, PSA has severe diagnostic limitations leading to unnecessary biopsies, over-diagnosis, and over-treatment, which drives patient anxiety, morbidities, and costs. Nevertheless, PSA is used as a de facto screening test for prostate cancer in many countries, including Sweden. There are substantial levels of opportunistic PSA testing in Sweden, with approximately half of Swedish men aged 55-69 years having had a PSA test. Improved screening strategies for prostate cancer are thus urgently needed.
Over the last 2.5 years, we conducted the population based diagnostic STHLM3 trial with 47,640 participants in Stockholm, prospectively evaluating the STHLM3 prostate cancer risk prediction algorithm (abbreviated S3M) based on a combination of biomarkers and clinical variables with the aim of improving testing for clinically significant prostate cancer (defined as Gleason 7 or higher) in men aged 50-69 years compared to PSA based testing. S3M is a step into a risk-based personalized prostate cancer testing program. However, several questions remains to be answered to optimally use S3M: (i) at what ages should testing start and stop, and how often should men be tested; (ii) how should S3M be used in a rebiopsy setting; (iii) how should S3M be used in conjunction with the advent of pre-biopsy prostate MRI. This application targets the first of these questions by addressing the following aims:
Aim 1. Characterization of men’s risk trajectory over time as well as the harms and benefits of prostate cancer testing conditional on PSA, age, S3M predicted risk, and testing frequency to determine the testing intervals that best balances benefits and harms on a population level.
Aim 2. Develop a risk prediction model for predicting future (5-year) prostate cancer risk.
Aim 3. Use the results from Aims 1 and 2 to determine individualized start/stop ages and testing intervals for prostate cancer screening that best balances harms and benefits for a given man.
S3M will in an initial phase be clinically implemented by the Stockholm County Council (Stockholms läns landsting, SLL) during Q4 2015 and 2016. With the expected ramp-up of the clinical implementation of S3M in the coming years, we have the opportunity to define guidelines of how the test should be used. To get start/stop ages and testing frequency right is crucial – too much testing drives costs and overdiagnosis/overtreatment whereas too little testing compromises the mortality advantage.
Very little research has been done on risk-based personalization of start/stop and screening frequency. This is a fundamental research question to improve prostate cancer screening in the modern era of affordable multiplexed biomarker assaying.
Our research proposal leverages unique, world-class data sources, and established collaborations with strong industrial and clinical partners (Thermo Fisher and SLL). It also exploits biobanked samples and existing cost-effective multiplexed biomarker analysis and genotyping pipelines. Given the political and clinical support of STHLM3, there is a concrete possibility that this proposal will support the planning of organized prostate cancer screening in the Stockholm county.
Funder: Vetenskapsrådet
Amount: SEK 5,976,000
Funding type: research
Funder scheme: Project grant
Start date: 2016-01-01
End date: 2019-12-31
Investigator: Martin Eklund
Institution: Karolinska Institutet
Funded outputs count: 5
Funder award ID: 2015-03292
OpenAlex ID: G489404364