Predictors of biological aggressiveness of prostate specific antigen screening detected prostate cancer.
OBJECTIVE
It is not known whether screening of asymptomatic men with prostate specific antigen (PSA) decreases the mortality of prostate cancer. We evaluated the extent to which PSA screening identifies clinically significant prostate cancer by analyzing markers of biological aggressiveness.


METHODS
We compared prostate cancer in 56 patients in the screening and 21 in the randomized control arm of a population based cohort of 8,975 men 55 to 67 years old participating in the Finnish arm of the European Randomized Study of Screening for Prostate Cancer to 47 clinically detected organ confined, 30 clinically detected metastatic and 16 latent prostate tumors identified at autopsy in 46 consecutive subjects. Biological aggressiveness was determined by histological grading using the Gleason and Mostofi scales, tumor proliferation rate by Ki-67 immunostaining, p53 over expression by immunostaining and aneuploidy by fluorescence in situ hybridization using formalin fixed, paraffin embedded tumor specimens.


RESULTS
A total of 56 neoplasms were detected in 2,781 men (2%) who participated 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 expression (p = 0.015) than screening detected disease. At least 1 feature of biological aggressiveness was present in 19% of latent, 34% of screening detected, 51% of clinically detected and organ confined, 62% of randomized control and 87% of metastasis cases. Of the screening detected tumors defined as biologically aggressive 74% were identified at organ confined stages pT1-2N0M0.


CONCLUSIONS
PSA screening detects a significant number of biologically aggressive cancers at an early clinical stage, implying that screening may decrease mortality.
Isola
J
J
Laboratory of Cancer Genetics, Institute of Medical Technology and School of Public Health, University of Tampere, Finland.
Auvinen
A
A
Poutiainen
M
M
Kakkola
L
L
Järvinen
T A
TA
Määttänen
L
L
Stenman
U H
UH
Tammela
T
T
Hakama
M
M
Visakorpi
T
T
D000368:Aged; D002455:Cell Division; D015331:Cohort Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D017430:Prostate-Specific Antigen