Predictors of biological aggressiveness of prostate specific antigen screening detected prostate cancer

Purpose: It is not known whether screening of asymptomatic men with prostat e specific antigen (PS4) decreases the mortality of prostate cancer. We eva luated the extent to which PSA screening identifies clinically significant prostate cancer by analyzing markers of biological aggressiveness. Materials and Methods: We compared prostate cancer in 56 patients in the sc reening and 21 in the randomized control arm of a population based cohort o f 8,975 men 55 to 67 years old participating in the Finnish arm of the Euro pean Randomized Study of Screening for Prostate Cancer to 47 clinically det ected organ confined, 30 clinically detected metastatic and 16 latent prost ate tumors identified at autopsy in 16 consecutive subjects. Biological agg ressiveness was determined by histological grading using the Gleason and Mo stofi scales, tumor proliferation rate by Ki-67 immunostaining, p53 over ex pression by immunostaining and aneuploidy by fluorescence in situ hybridiza tion using formalin fixed, paraffin embedded tumor specimens. Results: A total of 56 neoplasms were detected in 2,781 men (2%) who partic ipated in PSA screening and 21 were detected in 5,975 nonscreened controls (0.35%) during the study period. Disease in nonscreened controls more often involved a high tumor proliferation rate (p = 0.004) and p53 over expressi on (p = 0.015) than screening detected disease. At least 1 feature of biolo gical aggressiveness was present in 19% of latent, 34% of screening detecte d, 51% of clinically detected and organ confined, 62% of randomized control and 87% of metastasis cases. Of the screening detected tumors defined as b iologically aggressive 74% were identified at organ confined stages pT1-2N0 MO. Conclusions: PSA screening detects a significant number of biologically agg ressive cancers at an early clinical stage, implying that screening may dec rease mortality.