Urothelial Cancer The Extent of Lymphadenectomy Seems to Be Associated with Better Survival in Patients with Nonmetastatic Upper-Tract Urothelial Carcinoma: How Many Lymph Nodes Should Be Removed? Marco Roscigno a, *, Shahrokh F. Shariat b,1 , Vitaly Margulis e , Pierre Karakiewicz m , Mesut Remzi d , Eiji Kikuchi g , Richard Zigeuner h , Alon Weizer i , Arthur Sagalowsky b , Karim Bensalah l , Jay D. Raman k , Christian Bolenz f , Wassim Kassou f , Theresa M. Koppie j , Christopher G. Wood e , Jeffrey Wheat i , Cord Langner h , Casey K. Ng k , Umberto Capitanio m , Roberto Bertini a , Mario I. Ferna ´ndez c , Shuji Mikami g , Masaru Isida g , Philipp Stro ¨bel f , Francesco Montorsi a a Vita Salute University San Raffaele, Milan, Italy b University of Texas Southwestern Medical Center, Dallas, Texas, USA c Clinica Alemana de Santiago, Santiago, Chile d University of Vienna, Vienna, Austria e University of Texas M.D. Anderson Cancer Center, Houston, TX, USA f University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany g Keio University School of Medicine, Tokyo, Japan h Medical University Graz, Graz, Austria i University of Michigan, Ann Arbor, MI, USA j University of California Davis, Sacramento, CA, USA k Cornell University, New York, NY, USA l University of Rennes, Rennes, France m University of Montreal, Montreal, QC, Canada EUROPEAN UROLOGY 56 (2009) 512–519 available at www.sciencedirect.com journal homepage: www.europeanurology.com Article info Article history: Accepted June 8, 2009 Published online ahead of print on June 18, 2009 Keywords: Lymph node dissection Prognosis Urinary tract cancer Urothelial carcinoma Nephroureterectomy Survival Metastasis Abstract Background: The role and extent of lymphadenectomy in patients with upper- tract urothelial carcinoma (UTUC) is debated. Objective: To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC. Design, setting, and participants: The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006. Intervention: Patients were treated with RNU and lymphadenectomy. Measurements: Univariable and multivariable Cox proportional hazards regres- sion models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified. 1 Currently at Memorial Sloan-Kettering Cancer Center, New York, NY, USA. * Corresponding author. Vita Salute University San Raffaele, Via Olgettina 60, 20132, Milan, Italy. Tel. +39 2 2643 4199; Fax: +39 2 26437298. E-mail address: roscigno.marco@hsr.it (M. Roscigno). 0302-2838/$ – see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2009.06.004