The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level <2.5 ng/ml.

INTRODUCTION: It is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings. METHODS: Between 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N=1710) or palpable (T2-T4, N=7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA<2.5 ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM. RESULTS: After median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR=3.52; 95% CI: 1.25-9.89; P=.017) in men with T1c, Gleason score 7-10 PC, but decreased PCSM risk (AHR=0.66; 95% CI: 0.52-0.83; P<.001) for men with T2-T4 PC and any Gleason score. DISCUSSION: For men with diagnostic PSA level <2.5 ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA.