Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men

Abstract

Background: Prostate-specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening.

Methods: To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent PSA screening at 3 months (primary outcome), a randomized trial of FH versus GRS plus FH was conducted with 700 whites aged 40 to 49 years without prior PSA screening. Secondary outcomes included anxiety, recall, physician discussion at 3 months, and PSA screening at 3 years. Pictographs versus numeric presentations of genetic risk were also evaluated.

Results: At 3 months, no significant differences were observed in the rates of PSA screening between the FH arm (2.1%) and the GRS-FH arm (4.5% with GRS-FH vs. 2.1% with FH: χ² = 3.13, P = .077); however, PSA screening rates at 3 months significantly increased with given risk in the GRS-FH arm (P = .013). Similar results were observed for discussions with physicians at 3 months and PSA screening at 3 years. Average anxiety levels decreased after the individual cancer risk was provided (P = .0007), with no differences between groups. Visual presentation by pictographs did not significantly alter comprehension or anxiety.

Conclusions: This is likely the first randomized trial of multimarker genomic testing to report genomic targeting of cancer screening. This study found little evidence of concern about excess anxiety or overuse/underuse of PSA screening when multimarker genetic risks were provided to patients. Cancer 2016;122:3564-3575. © 2016 American Cancer Society.

Keywords: genetic counseling; genetic risk score; genetic testing; prostate cancer; prostate-specific antigen (PSA) screening; randomized controlled trial.

Figure 1. Study design, enrollment, and outcomes

Figure 2. Distribution of Genetic Risk Scores Given to Study Participants in FH (A) and GRS+FH (B) arms

Red bars represent the percentage of participants given a specific risk value. Black dashed line at 18.3% represents the average risk that was also provided on each participant risk report.

Figure 2. Distribution of Genetic Risk Scores Given to Study Participants in FH (A) and GRS+FH (B) arms

Red bars represent the percentage of participants given a specific risk value. Black dashed line at 18.3% represents the average risk that was also provided on each participant risk report.

Figure 3. Participant health behaviors, in FH and GRS+FH arms, stratified by given risk

Black bars represent the percentage of participants that reported engaging in health behaviors during three month follow-up. Blue bars represent these same percentages, but stratified by category of given risk. Risk categories are <1, 1-2, 2-3, and >3-fold higher than the population average of 18.3% (categories were 0-17%, 18-35%, 37-54%, 55-80%, respectively) a. Discussed PSA screening with physician per self-report during 3 month follow-up. b. Engaged in PSA screening per self-report during 3 month follow-up. c. Engaged in PSA screening, per medical record review, during 3 years of follow-up.

Figure 3. Participant health behaviors, in FH and GRS+FH arms, stratified by given risk

Black bars represent the percentage of participants that reported engaging in health behaviors during three month follow-up. Blue bars represent these same percentages, but stratified by category of given risk. Risk categories are <1, 1-2, 2-3, and >3-fold higher than the population average of 18.3% (categories were 0-17%, 18-35%, 37-54%, 55-80%, respectively) a. Discussed PSA screening with physician per self-report during 3 month follow-up. b. Engaged in PSA screening per self-report during 3 month follow-up. c. Engaged in PSA screening, per medical record review, during 3 years of follow-up.

Figure 3. Participant health behaviors, in FH and GRS+FH arms, stratified by given risk

Black bars represent the percentage of participants that reported engaging in health behaviors during three month follow-up. Blue bars represent these same percentages, but stratified by category of given risk. Risk categories are <1, 1-2, 2-3, and >3-fold higher than the population average of 18.3% (categories were 0-17%, 18-35%, 37-54%, 55-80%, respectively) a. Discussed PSA screening with physician per self-report during 3 month follow-up. b. Engaged in PSA screening per self-report during 3 month follow-up. c. Engaged in PSA screening, per medical record review, during 3 years of follow-up.