Stratification of High-risk Prostate Cancer into Prognostic Categories: A European Multi-institutional Study
Joniau S1, Briganti A2, Gontero P3, Gandaglia G2, Tosco L4, Fieuws S5, Tombal B6, Marchioro G7, Walz J8, Kneitz B9, Bader P10, Frohneberg D10, Tizzani A3, Graefen M8, van Cangh P5, Karnes RJ11, Montorsi F2, Van Poppel H4, Spahn M12; European Multicenter Prostate Cancer Clinical and Translational Research Group (EMPaCT). Eur Urol. 2014 Jan 25. pii: S0302-2838(14)00071-2. doi: 10.1016/j.eururo.2014.01.020. [Epub ahead of print]

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1Department of Urology, University Hospitals, Leuven, Belgium. Electronic address: 2San Raffaele Scientific Institute, Urological Research Institute, Department of Urology, Milan, Italy. 3Department of Urology, University of Turin, Turin, Italy. 4Department of Urology, University Hospitals, Leuven, Belgium. 5Department of Biostatistics, University Hospitals, Leuven, Belgium. 6Department of Urology, Université Catholique de Louvain, Brussels, Belgium. 7Department of Urology, University of Piemonte Orientale, Novarra, Italy. 8Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany. 9Department of Urology, Julius Maximilians Universität Würzburg, Würzburg, Germany. 10Department of Urology, Community Hospital Karlsruhe, Karlsruhe, Germany. 11Department of Urology, Mayo Clinic, Rochester, MN, USA. 12Department of Urology, University of Bern, Bern, Switzerland.


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.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers.

INTERVENTION: Retropubic radical prostatectomy with pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (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.

RESULTS AND LIMITATIONS: The simplified model yielded an R2 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 (R2: 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.