352 TIME TO DISEASE PROGRESSION IS NOT AN APPROPRIATE ENDPOINT IN STUDIES OF IMMEDIATE VERSUS DEFERRED/SALVAGE ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 2011352 TIME TO DISEASE PROGRESSION IS NOT AN APPROPRIATE ENDPOINT IN STUDIES OF IMMEDIATE VERSUS DEFERRED/SALVAGE ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Urs Studer, Peter Whelan, Florian Wimpissinger, Jacques Casselman, Theo M. De Reijke, Harmut Kn̈onagel, Stefan Madersbacher, Santiago Isorna, Subramanian K. Sundaram, and Laurence Collette Urs StuderUrs Studer Bern, Switzerland More articles by this author , Peter WhelanPeter Whelan Leeds, United Kingdom More articles by this author , Florian WimpissingerFlorian Wimpissinger Vienna, Austria More articles by this author , Jacques CasselmanJacques Casselman Oostende, Belgium More articles by this author , Theo M. De ReijkeTheo M. De Reijke Amsterdam, Netherlands More articles by this author , Harmut Kn̈onagelHarmut Kn̈onagel Zürich, Switzerland More articles by this author , Stefan MadersbacherStefan Madersbacher Linz, Austria More articles by this author , Santiago IsornaSantiago Isorna Las Palmas de Gran Canaria, Spain More articles by this author , Subramanian K. SundaramSubramanian K. Sundaram Wakefield, United Kingdom More articles by this author , and Laurence ColletteLaurence Collette Brussels, Belgium More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.437AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent trials assessing the benefit of immediate androgen deprivation therapy (ADT) in prostate cancer often do so based on differences in time to progression. We argue that time to progression is not an appropriate trial endpoint endpoint because it does not account for the mechanism of androgen refractoriness, that itself may impact the effectiveness of further salvage therapies. METHODS EORTC trial 30891 compared immediate ADT (n=492 pts) with orchiectomy or LH-RH analog to deferred ADT (n=493 pts) initiated at the time of symptomatic disease progression or life-threatening complications in patients with T0–4 N0–2 M0 prostate cancer. Overall survival was primary endpoint, prostate cancer mortality, time to first objective progression (metastases documented on imaging or by significant rise in alkaline phosphatase or by doubling serum PSA value above 20 ng/ml within 1 year) and time to ADT refractory progression were secondary endpoints. We contrast the treatment difference observed on these endpoints with the purpose to challenge surrogacy. RESULTS Overall, 362 of 985 patients had objective disease progression on study, 291 had ADT refractory progression, 769 patients died (78.1%) with prostate cancer being the cause for 269 (27.3%). Deferred ADT was significantly worse than immediate ADT for time to first disease progression (P<0.0001) with 10-year progression rates of 40.5% vs 27.2%, resp. However, time to ADT refractory progression after did not differ significantly (P=0.64,fig.1) and prostate cancer mortality was also not improved with immediate ADT (fig.2). CONCLUSIONS Time to first disease progression should not be used to assess the eventual benefit of immediate ADT compared to waiting deferred treatment approach. A survival endpoint should be used instead. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e143 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Urs Studer Bern, Switzerland More articles by this author Peter Whelan Leeds, United Kingdom More articles by this author Florian Wimpissinger Vienna, Austria More articles by this author Jacques Casselman Oostende, Belgium More articles by this author Theo M. De Reijke Amsterdam, Netherlands More articles by this author Harmut Kn̈onagel Zürich, Switzerland More articles by this author Stefan Madersbacher Linz, Austria More articles by this author Santiago Isorna Las Palmas de Gran Canaria, Spain More articles by this author Subramanian K. Sundaram Wakefield, United Kingdom More articles by this author Laurence Collette Brussels, Belgium More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...