title: Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.
abstract: 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%.
authors.affiliation: Carl-Thiem-Klinikum Cottbus, Department of Urology, Cottbus, Germany. Electronic address: i.wolff@ctk.de.
authors.forename: I
authors.initials: I
authors.lastname: Wolff
authors.affiliation: St. Elisabeth-Klinikum Straubing, Department of Urology, Straubing, Germany.
authors.forename: M
authors.initials: M
authors.lastname: May
authors.affiliation: Carl-Thiem-Klinikum Cottbus, Department of Urology, Cottbus, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hoschke
authors.affiliation: Medizinische Universität zu Graz, Department of Urology, Graz, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Zigeuner
authors.affiliation: Pio Da Pietrelcina Hospital, Department of Urology, Vasto, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cindolo
authors.affiliation: Medizinische Universität zu Graz, Department of Urology, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Hutterer
authors.affiliation: Pio Da Pietrelcina Hospital, Department of Urology, Vasto, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Schips
authors.affiliation: European Institute of Oncology, Division of Urology, Milan, Italy.
authors.forename: O
authors.initials: O
authors.lastname: De Cobelli
authors.affiliation: Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Department of Urology, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Rocco
authors.affiliation: Faculty of Health Sciences, University "La Sapienza", Ospedale Sant'Andrea, Department of Urology, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: De Nunzio
authors.affiliation: Faculty of Health Sciences, University "La Sapienza", Ospedale Sant'Andrea, Department of Urology, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tubaro
authors.affiliation: Clinical Municipal Hospital, Department of Urology, Cluj-Napoca, Romania.
authors.forename: I
authors.initials: I
authors.lastname: Coman
authors.affiliation: Clinical Municipal Hospital, Department of Urology, Cluj-Napoca, Romania.
authors.forename: B
authors.initials: B
authors.lastname: Feciche
authors.affiliation: Klinikum Dortmund, Department of Urology, Dortmund, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Truss
authors.affiliation: Medizinische Universität zu Graz, Department of Urology, Graz, Austria.
authors.forename: O
authors.initials: O
authors.lastname: Dalpiaz
authors.affiliation: Washington University School of Medicine, Department of Surgery, Division of Urologic Surgery, St. Louis, Washington, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Figenshau
authors.affiliation: Washington University School of Medicine, Department of Surgery, Division of Urologic Surgery, St. Louis, Washington, USA.
authors.forename: K
authors.initials: K
authors.lastname: Madison
authors.affiliation: Hospital Universitario Principe de Asturias, Alcala de Henares, Department of Urology, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Chapado
authors.affiliation: Hospital Universitario Principe de Asturias, Alcala de Henares, Department of Urology, Madrid, Spain.
authors.forename: M D C
authors.initials: MD
authors.lastname: Santiago Martin
authors.affiliation: G. Rummo Hospital, Department of Urology, Benevento, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Salzano
authors.affiliation: G. Rummo Hospital, Department of Urology, Benevento, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lotrecchiano
authors.affiliation: Medical University of Vienna, Department of Urology, Vienna, Austria.
authors.forename: S F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Ruprecht-Karls-Universität Heidelberg, Department of Urology, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hohenfellner
authors.affiliation: Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Waidelich
authors.affiliation: Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stief
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Urology, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Miller
authors.affiliation: Ruprecht-Karls-Universität Heidelberg, Department of Urology, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Pahernik
authors.affiliation: Ludwig-Maximilians-Universität München, Department of Urology, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Brookman-May
mesh_terms: D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D003952:Diagnostic Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009392:Nephrectomy; D058996:Quality Improvement; D018570:Risk Assessment; D016896:Treatment Outcome
keywords: Adjuvant therapy; Disease recurrence; Nephrectomy; Phase-3-trials; Renal cell cancer; Targeted agents