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Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy
Authors:Jeffery C Wheat  Alon Z Weizer  J Stuart Wolf  Yair Lotan  Mesut Remzi  Vitaly Margulis  Christopher G Wood  Francesco Montorsi  Marco Roscigno  Eiji Kikuchi  Richard Zigeuner  Cord Langner  Christian Bolenz  Theresa M Koppie  Jay D Raman  Mario Fernández  Pierre Karakiewizc  Umberto Capitanio  Karim Bensalah  Jean-Jacques Patard  Shahrokh F Shariat
Institution:1. University of Michigan, Ann Arbor, MI 48109, USA;2. University of Texas-Southwestern, Dallas, Texas 75390, USA;3. Medical University of Vienna, Vienna, Austria;4. University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;5. Vita-Salute University, Milan, Italy;6. Keio University School of Medicine, Tokyo, Japan;7. Medical University Graz, Graz, Austria;8. Universitätsklinikum Mannheim, Mannheim, Germany;9. University of California-Davis, Sacramento, CA 95817, USA;10. Weill Cornell Medical College, New York, NY 10065, USA;11. Clinica Alemana de Santiago, Santiago, Chile;12. University of Montreal, Montreal, Quebec, Canada;13. University of Rennes, Rennes, France;14. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Abstract:ObjectiveCarcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC).Materials and methodsA multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower.ResultsConcomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients.ConclusionThe presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.
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