title: Algorithms in the First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma--Analysis Using Diagnostic Nodes.
abstract: BACKGROUND
  With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field.
  
  
  METHODS
  Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified.
  
  
  RESULTS
  The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria).
  
  
  CONCLUSIONS
  In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts.
  
  
  CONCLUSIONS
  The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside a clinical trial; however, the data highlight the different treatment options and the criteria used to select them. The diversity in decision making and how results from phase III trials can be interpreted and implemented differently in daily practice are demonstrated.
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland christian.rothermundt@kssg.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Rothermundt
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bailey
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerbone
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: McDermott
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Brian
authors.initials: B
authors.lastname: Rini
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Cora
authors.initials: C
authors.lastname: Sternberg
authors.affiliation: Division of Haematology and Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy; Department of Oncology, Cambridge University Hospitals National Health Service Foundation, Cambridge, United Kingdom; Gustave Roussy, Villejuif, France; Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany; The Royal Marsden Hospital, London, United Kingdom; Department of Oncology, Akershus University Hospital and Medical Faculty of University of Oslo, Oslo, Norway; Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA; Abteilung für Onkologie, Allgemeines Krankenhaus-Universitätskliniken, Wien, Austria; Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Putora
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D003663:Decision Trees; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis
keywords: Algorithm; Decision criteria; Renal cell carcinoma; Treatment