Urologic Oncology: Seminars and Original Investigations ] (2013) ∎∎∎–∎∎∎ Seminar article Considerations on the use of urine markers in the management of patients with low-/intermediate-risk non–muscle invasive bladder cancer Bernd J. Schmitz-Dräger, M.D., Ph.D. a,b, * , Tilman Todenhöfer, M.D. c , Bas van Rhijn, M.D. d , Beate Pesch, Ph.D. e ,Mĺiss A. Hudson, M.D. f , Ashish Chandra, M.D. g , Molly A. Ingersoll, M.D., Ph.D. h , Wassim Kassouf, M.D. i , Joan Palou, M.D. j , John Taylor, M.D. k , Antonia Vlahou, Ph.D. l , Thomas Behrens, M.D. e,q , Rossana Critelli, Ph.D. m,n , H.Barton Grossman, M.D. o , Marta Sanchez-Carbayo, Ph.D. p , Ashish Kamat, M.D. o a Urologie24, Fürth, Germany b Schön Klinik Nürnberg/Fürth, Fürth, Germany c Urologische Universitätsklinik, Eberhard Karls Universität, Tübingen, Germany d Division of Surgical Oncology (Urology), Antoni van Leeuwenhoek Hospital, Netherlands Cancer Institute, Amsterdam, The Netherlands e Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University, Bochum, Germany f Ochsner Clinic Foundation, Tom and Gayle Benson Cancer Center, New Orleans, LA g Cellular Pathology, St Thomas' Hospital, London, UK h Department of Immunology, Institute Pasteur and U818 Inserm, Paris, France i McGill University Health Center, Montreal, Canada j Servicio de Urología, Fundación Puigvert, Barcelona, Spain k Division of Urology, University of Connecticut Health Center, Farmington, CT l Division of Biotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece m Department of Genetics, Biology and Biochemistry, Universita di Torino, Torino, Italy n HuGeF—Human Genetics Foundation, Torino, Italy o Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX p CIC bioGUNE, Bilbao, Spain q Protein Research Unit Ruhr within Europe (PURE), Ruhr-Universität, Bochum, Germany Abstract Objectives: Many molecular assays for bladder cancer diagnosis and surveillance have been developed over the past several decades. However, none of these markers have been routinely implemented into clinical decision making. Beyond their potential for screening high-risk populations, urine markers likely have the greatest potential in the follow-up of patients with non–muscle invasive bladder cancer (NMIBC). Methods: Here, we discuss the current options and limitations of the use of urine markers for patient surveillance, focusing on patients with low-/intermediate-risk NMIBC. Results: As these patients have a very low risk of tumor progression, the primary goal of surveillance is detection of recurrent disease. Although urine cytology seems to be limited to detection of few patients who would develop high-grade tumors, we conclude that the use of markers with high sensitivity for low-grade disease for patient follow-up has the potential to decrease the frequency of urethrocystoscopy without compromising patient prognosis. Because a single marker may not have sufficient sensitivity for detection of low-grade tumors, different scenarios, e.g., multitesting and reflex or sequential approaches, are discussed. Conclusions: There is consensus that currently available markers have the potential to support clinical decision making in follow-up of patients with low-/intermediate-risk NMIBC. In light of our analysis, further additional randomized controlled studies to effectively assess the clinical usefulness of modern urine markers are required. r 2013 Elsevier Inc. All rights reserved. Keywords: Urine markers; Non–muscle invasive bladder cancer; Low risk; Disease management; Costs 1078-1439/$ – see front matter r 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.urolonc.2013.10.010 This article reflects and summarizes discussions held at the 10th Meeting of the International Bladder Cancer Network (IBCN e.V.), Nijmegen, The Netherlands, 20 to 22.9.2012. * Corresponding author. Tel.: þ49-911-971-4531; fax: þ49-911-971-4532. E-mail address: bernd_sd@yahoo.de (B.J. Schmitz-Dräger).