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

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 riskassociated 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.

A genetic risk assessment for prostate cancer influences patients’ risk perception and use of repeat PSA testing: a cross-sectional study in Danish general practice

“…This is even more evident for patients who were not aware of their normal (that is, non-elevated) genetic risk, but still had fewer PSA tests within 2 years. 23 The relatively smaller indirect effect through perceived risk is consistent with earlier studies that found limited effects of long-term genetic testing on perceived risk. 32…”

“…In a study of the same cohort by a number of the present authors, 23 a strong association between the genetic risk and whether a patient had a repeat PSA test was observed. Accordingly, 83.6% (61 out of 73) of patients with a high genetic risk had a repeat PSA test within 2 years, while 20.5% (99 out of 487) of patients with a normal risk had a repeat PSA test (Δ = 0.63; t-test, P<0.001; 95% CI = 0.54 to 0.72).…”

“…Based on genotyping of 33 risk loci and/or SNPs (adjusted for age and PC family history), the individual lifetime PC risk was calculated for each participant as previously described, 21,23 and results reported as high, normal, or unknown risk. As the lifetime risk score was adjusted for age in the algorithm, no further distinction was made between younger and older participants.…”

“…Second, this report did not focus on the effect of the intervention on overall PSA test usage, as this has already been addressed elsewhere. 23 Future studies should assess both the effects of communication strategies and offering a genetic test for lifetime PC risk on the number of PC diagnoses. Ideally, such future studies should include an optimised genetic test that includes all currently known PC risk variants.…”

Blood and urine biomarkers in prostate cancer: Are we ready for reflex testing in men with an elevated prostate-specific antigen?

“…As more than 200 PCa risk-associated single-nucleotide polymorphisms (SNPs) have been identified through large genome-wide association studies (GWASs), more SNP-based PCa tests are being developed [ 78 , 79 ]. Although individual SNPs by themselves do not have significant disease predictive value, when combined, polygenic SNPs panels can be a useful in risk stratifying individuals that are likely to have PCa.…”