BACKGROUND - Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting.
We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients.
METHODS - The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index.
RESULTS - During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%).
CONCLUSIONS - Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2016 Jan 22 [Epub ahead of print]
I Wolff, M May, B Hoschke, R Zigeuner, L Cindolo, G Hutterer, L Schips, O De Cobelli, B Rocco, C De Nunzio, A Tubaro, I Coman, B Feciche, M Truss, O Dalpiaz, R S Figenshau, K Madison, M Sánchez-Chapado, M D C Santiago Martin, L Salzano, G Lotrecchiano, S F Shariat, M Hohenfellner, R Waidelich, C Stief, K Miller, S Pahernik, S Brookman-May, Members of the CORONA Project and the European Association of Urology (EAU) Young Academic Urologists (YAU) Renal Cancer Group
Carl-Thiem-Klinikum Cottbus, Department of Urology, Cottbus, Germany. St. Elisabeth-Klinikum Straubing, Department of Urology, Straubing, Germany., Carl-Thiem-Klinikum Cottbus, Department of Urology, Cottbus, Germany., Medizinische Universität zu Graz, Department of Urology, Graz, Austria., Pio Da Pietrelcina Hospital, Department of Urology, Vasto, Italy., Medizinische Universität zu Graz, Department of Urology, Graz, Austria., Pio Da Pietrelcina Hospital, Department of Urology, Vasto, Italy., European Institute of Oncology, Division of Urology, Milan, Italy., Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Department of Urology, Milan, Italy., Faculty of Health Sciences, University "La Sapienza", Ospedale Sant'Andrea, Department of Urology, Rome, Italy., Faculty of Health Sciences, University "La Sapienza", Ospedale Sant'Andrea, Department of Urology, Rome, Italy., Clinical Municipal Hospital, Department of Urology, Cluj-Napoca, Romania., Clinical Municipal Hospital, Department of Urology, Cluj-Napoca, Romania., Klinikum Dortmund, Department of Urology, Dortmund, Germany., Medizinische Universität zu Graz, Department of Urology, Graz, Austria., Washington University School of Medicine, Department of Surgery, Division of Urologic Surgery, St. Louis, Washington, USA., Washington University School of Medicine, Department of Surgery, Division of Urologic Surgery, St. Louis, Washington, USA., Hospital Universitario Principe de Asturias, Alcala de Henares, Department of Urology, Madrid, Spain., Hospital Universitario Principe de Asturias, Alcala de Henares, Department of Urology, Madrid, Spain., G. Rummo Hospital, Department of Urology, Benevento, Italy., G. Rummo Hospital, Department of Urology, Benevento, Italy., Medical University of Vienna, Department of Urology, Vienna, Austria., Ruprecht-Karls-Universität Heidelberg, Department of Urology, Heidelberg, Germany., Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany., Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany., Charité-Universitätsmedizin Berlin, Department of Urology, Berlin, Germany., Ruprecht-Karls-Universität Heidelberg, Department of Urology, Heidelberg, Germany., Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany.