Gene based prediction of clinically localized prostate cancer progression after radical prostatectomy.
OBJECTIVE
Accurate estimates of recurrence risk are needed for optimal treatment of patients with clinically localized prostate cancer. We combined an established nomogram and what to our knowledge are novel molecular predictors into a new prognostic model of prostate specific antigen recurrence.


METHODS
We analyzed gene expression profiles from formalin fixed, paraffin embedded, localized prostate cancer tissues to identify genes associated with prostate specific antigen recurrence. Profiles of the identified markers were reproduced by reverse transcriptase-polymerase chain reaction. We used the profiles of 3 of these genes along with output from the Kattan postoperative nomogram to produce a predictive model of prostate specific antigen recurrence.


RESULTS
After variable selection we built a model of prostate specific antigen recurrence combining expression values of 3 genes and the postoperative nomogram. The 3-gene plus nomogram model predicted 5-year prostate specific antigen recurrence with a concordance index of 0.77 in a validation set compared to a concordance index of 0.67 for the nomogram. This model identified a subgroup of patients at high risk for recurrence that was not identified by the nomogram.


CONCLUSIONS
This new gene based classifier has superior predictive power compared to that of the 5-year nomogram to assess the risk of prostate specific antigen recurrence in patients with organ confined prostate cancer. Our classifier should provide more accurate stratification of patients into high and low risk groups for treatment decisions and adjuvant clinical trials.
Talantov
Dmitri
D
Veridex LLC, Raritan, New Jersey, USA.
Jatkoe
Timothy A
TA
Böhm
Maret
M
Zhang
Yi
Y
Ferguson
Alison M
AM
Stricker
Phillip D
PD
Kattan
Michael W
MW
Sutherland
Robert L
RL
Kench
James G
JG
Wang
Yixin
Y
Henshall
Susan M
SM
D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics*; D049451:Nomograms; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018570:Risk Assessment