Presentation Authors: Alexandra Berger*, Boston, MA, Garrick Aden-Buie, Tampa, FL, Adam Kibel, Lorelei Mucci, Kathryn Penney, Kathryn Wilson, Boston, MA, Travis Gerke, Tampa, FL, Mark Preston, Boston, MA
Introduction: PSA screening has been shown to reduce prostate cancer (PCa) mortality, but is associated with overdiagnosis. Risk-stratified screening might minimize harms of overtreatment while identifying aggressive PCa in time for cure. We sought to determine which men are low-risk and might forgo screening beyond age 60, and to define a high-risk group where PSA testing beyond age 70 may provide benefit.
Methods: We used the PLCO trial with 13-yr follow-up to identify 27,656 men in the screening arm with baseline PSA and outcome data. 11,366 (41%) men were age 60(+/- 2.5yr), 9,910 (35%) were age 65(+-2.5yr) and 6,380 (23%) were age 70(+/-2.5yr). As in a prior paper, we used the Physicians Health Study to identify PSA percentiles by age amongst controls who did not develop PCa over the 30-yr follow-up. Median PSA (ng/ml) for those age 60 was 1.0, age 65 was 1.5 and age 70 was 1.5. With PSA below median as reference, these percentile groupings were used to estimate risk of aggressive PCa (Gleason >=7, Stage >=3, metastatic disease or PCa death) or PCa death.
Results: Amongst men age 60 with PSA=2-4 (75th-90th percentile), 188 (11.7%) developed aggressive PCa compared to 57 (1.1%) with PSA < 1 ( < 50th percentile) (HR 10.7, 95%CI 8.0-14.5, p < 0.001). Furthermore, men age 60 with PSA>=2 had an absolute risk of PCa death of 0.7% vs. 0.1% for men with PSA < 1 (HR 6.75, 95%CI 2.4-19.4, p < 0.001). This absolute risk increased to 1.4% for men with PSA>=4 (>=90th percentile). Amongst men age 70 with PSA=3-5 (75th-90th percentile), 102 (14.4%) developed aggressive PCa compared to 65 (2.1%) with PSA < 1.5 ( < 50th percentile) (HR 7.1, 95%CI 5.2-9.7, p < 0.001). Furthermore, men age 70 with PSA>=3 had an absolute risk of PCa death of 0.7% vs. 0.2% for men with PSA < 1.5 (HR 3.4, 95%CI 1.04-11.2, p=0.04). This absolute risk increased to 3.4% for men with PSA>=5 (>=90th percentile).
Conclusions: PSA at age 60-70 strongly predicts risk of aggressive PCa and PCa death in a US screening trial over 13 years. This supports risk-stratified screening with consideration of exempting men with PSA below the median at age 60 from further screening. However, healthy men age 70 with PSA levels in the upper quartile are at risk for aggressive PCa and should consider shared decision making regarding ongoing PSA testing.