Stratification of High-risk Prostate Cancer into Prognostic Categories: A European Multi-institutional Study

Abstract

BackgroundHigh-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory. ObjectiveTo develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors. Design, setting, and participantsWe conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers. InterventionRetropubic radical prostatectomy with pelvic lymphadenectomy. Outcome measurements and statistical analysisTwo 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. Results and limitationsThe 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. ConclusionsThis 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.