The effect of assessing genetic risk of prostate cancer on the use of PSA tests in primary care: A cluster randomized controlled trial

PLoS Med. 2020 Feb 7;17(2):e1003033. doi: 10.1371/journal.pmed.1003033. eCollection 2020 Feb.

Abstract

Background: Assessing genetic lifetime risk for prostate cancer has been proposed as a means of risk stratification to identify those for whom prostate-specific antigen (PSA) testing is likely to be most valuable. This project aimed to test the effect of introducing a genetic test for lifetime risk of prostate cancer in general practice on future PSA testing.

Methods and findings: We performed a cluster randomized controlled trial with randomization at the level of general practices (73 in each of two arms) in the Central Region (Region Midtjylland) of Denmark. In intervention practices, men were offered a genetic test (based on genotyping of 33 risk-associated single nucleotide polymorphisms) in addition to the standard PSA test that informed them about lifetime genetic risk of prostate cancer and distinguished between "normal" and "high" risk. The primary outcome was the proportion of men having a repeated PSA test within 2 years. A multilevel logistic regression model was used to test the association. After applying the exclusion criteria, 3,558 men were recruited in intervention practices, with 1,235 (34.7%) receiving the genetic test, and 4,242 men were recruited in control practices. Men with high genetic risk had a higher propensity for repeated PSA testing within 2 years than men with normal genetic risk (odds ratio [OR] = 8.94, p < 0.01). The study was conducted in routine practice and had some selection bias, which is evidenced by the relatively large proportion of younger and higher income participants taking the genetic test.

Conclusions: Providing general practitioners (GPs) with access to a genetic test to assess lifetime risk of prostate cancer did not reduce the overall number of future PSA tests. However, among men who had a genetic test, knowledge of genetic risk significantly influenced future PSA testing.

Trial registration: This study is registered with ClinicalTrials.gov, number NCT01739062.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Early Detection of Cancer / statistics & numerical data*
  • Genetic Testing*
  • Humans
  • Kallikreins / blood*
  • Logistic Models
  • Male
  • Middle Aged
  • Multilevel Analysis
  • Polymorphism, Single Nucleotide
  • Primary Health Care
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Risk Assessment

Substances

  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT01739062

Grants and funding

This study was supported by grants from the Danish Research Council for Strategic Research (Journal no. 10-092796), the Sector Skills Council for Quality and Postgraduate Training (KEU) (Journal no. 1-30-72-93-11), the Danish Cancer Society, and The Velux Foundation (Veluxfonden). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.