Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study.
BACKGROUND
High-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory.


OBJECTIVE
To develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors.


METHODS
We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers.


METHODS
Retropubic radical prostatectomy with pelvic lymphadenectomy.


METHODS
Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (GS) (2-7 vs 8-10), and prostate-specific antigen (PSA; ≤ 20 ng/ml vs > 20 ng/ml). The first "extended" model includes all seven possible combinations; the second "simplified" model includes three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (GS 8-10 in combination with at least one other high-risk factor). The predictive accuracy of the models was summarized and compared. Survival estimates and clinical and pathologic outcomes were compared between the three subgroups.


CONCLUSIONS
The simplified model yielded an R(2) of 33% with a 5-yr area under the curve (AUC) of 0.70 with no significant loss of predictive accuracy compared with the extended model (R(2): 34%; AUC: 0.71). The 5- and 10-yr PCSS rates were 98.7% and 95.4%, 96.5% and 88.3%, 88.8% and 79.7%, for the good, intermediate, and poor prognosis subgroups, respectively (p = 0.0003). Overall survival, clinical progression-free survival, and histopathologic outcomes significantly worsened in a stepwise fashion from the good to the poor prognosis subgroups. Limitations of the study are the retrospective design and the long study period.


CONCLUSIONS
This study presents an intuitive and easy-to-use stratification of high-risk PCa into three prognostic subgroups. The model is useful for counseling and decision making in the pretreatment setting.
Department of Urology, University Hospitals, Leuven, Belgium. Electronic address: steven.joniau@uzleuven.be.
Steven
S
Joniau
San Raffaele Scientific Institute, Urological Research Institute, Department of Urology, Milan, Italy.
Alberto
A
Briganti
Department of Urology, University of Turin, Turin, Italy.
Paolo
P
Gontero
San Raffaele Scientific Institute, Urological Research Institute, Department of Urology, Milan, Italy.
Giorgio
G
Gandaglia
Department of Urology, University Hospitals, Leuven, Belgium.
Lorenzo
L
Tosco
Department of Biostatistics, University Hospitals, Leuven, Belgium.
Steffen
S
Fieuws
Department of Urology, Université Catholique de Louvain, Brussels, Belgium.
Bertrand
B
Tombal
Department of Urology, University of Piemonte Orientale, Novarra, Italy.
Giansilvio
G
Marchioro
Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany.
Jochen
J
Walz
Department of Urology, Julius Maximilians Universität Würzburg, Würzburg, Germany.
Burkhard
B
Kneitz
Department of Urology, Community Hospital Karlsruhe, Karlsruhe, Germany.
Pia
P
Bader
Department of Urology, Community Hospital Karlsruhe, Karlsruhe, Germany.
Detlef
D
Frohneberg
Department of Urology, University of Turin, Turin, Italy.
Alessandro
A
Tizzani
Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany.
Markus
M
Graefen
Department of Biostatistics, University Hospitals, Leuven, Belgium.
Paul
P
van Cangh
Department of Urology, Mayo Clinic, Rochester, MN, USA.
R Jeffrey
RJ
Karnes
San Raffaele Scientific Institute, Urological Research Institute, Department of Urology, Milan, Italy.
Francesco
F
Montorsi
Department of Urology, University Hospitals, Leuven, Belgium.
Hein
H
Van Poppel
Department of Urology, University of Bern, Bern, Switzerland.
Martin
M
Spahn
D000368:Aged; D019540:Area Under Curve; D018572:Disease-Free Survival; D005060:Europe; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000145:classification* / Q000473:pathology*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D015996:Survival Rate
D017430:Prostate-Specific Antigen
High-risk prostate cancer; Locally advanced prostate cancer; Risk groups; Risk stratification