External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome.
BACKGROUND
Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort.


OBJECTIVE
To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa).


METHODS
Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study.


METHODS
All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5-10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies).


METHODS
PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically.


CONCLUSIONS
Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p≤0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73-0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers.


CONCLUSIONS
In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated.
Auprich
Marco
M
Department of Urology, Medical University Graz, Austria. marco.auprich@medunigraz.at
Haese
Alexander
A
Walz
Jochen
J
Pummer
Karl
K
de la Taille
Alexandre
A
Graefen
Markus
M
de Reijke
Theo
T
Fisch
Margit
M
Kil
Paul
P
Gontero
Paolo
P
Irani
Jacques
J
Chun
Felix K-H
FK
D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D001706:Biopsy; D006801:Humans; D008297:Male; D049451:Nomograms; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000453:epidemiology / Q000473:pathology / Q000652:urine; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000652:urine; D015203:Reproducibility of Results; D012307:Risk Factors
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human