The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group.
OBJECTIVE
The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study.


METHODS
We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing.


RESULTS
The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005).


CONCLUSIONS
Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.
Vickers
Andrew J
AJ
Memorial Sloan-Kettering Cancer Center, New York, NY, USA. vickersa@mskcc.org
Cronin
Angel M
AM
Roobol
Monique J
MJ
Hugosson
Jonas
J
Jones
J Stephen
JS
Kattan
Michael W
MW
Klein
Eric
E
Hamdy
Freddie
F
Neal
David
D
Donovan
Jenny
J
Parekh
Dipen J
DJ
Ankerst
Donna
D
Bartsch
George
G
Klocker
Helmut
H
Horninger
Wolfgang
W
Benchikh
Amine
A
Salama
Gilles
G
Villers
Arnauld
A
Freedland
Steve J
SJ
Moreira
Daniel M
DM
Schröder
Fritz H
FH
Lilja
Hans
H
D000368:Aged; D001706:Biopsy; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000473:pathology*; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States
D017430:Prostate-Specific Antigen