Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort

In a large, international cohort, men with indications for prostate biopsy have an increased risk of high-grade prostate cancer in the presence of a family history of prostate cancer, second-degree prostate cancer, and first-degree breast cancer, controlling for other risk factors. This risk did not vary based on prostate-specific antigen level, and having additional affected relatives conferred an increased risk of high-grade prostate cancer on biopsy. The risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort. To estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer. This is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history. Multivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories. A first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57−2.00, p < 0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07−1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01−1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy. Men with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors. In a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.