Ilaria Lucca1, Wassim Kassouf2, Anil Kapoor3, Adrian Fairey4, Ricardo A Rendon5, Jonathan I Izawa6, Peter C Black7, Harun Fajkovic8, Christian Seitz8, Mesut Remzi9, Peter Nyirády10, Morgan Rouprêt11, Vitaly Margulis12, Yair Lotan12, Michela de Martino8, Sebastian L Hofbauer8, Pierre I Karakiewicz13, Alberto Briganti14, Giacomo Novara15, Shahrokh F Shariat12,16, Tobias Klatte8. 1. Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 2. Department of Urology, McGill University, Montreal, QC, Canada. 3. Department of Urology, McMaster University, Hamilton, ON, Canada. 4. Department of Surgery (Urology), University of Alberta, Edmonton, AB, Canada. 5. Department Urology, Dalhousie University, Halifax, NS, Canada. 6. Department of Surgery (Urology), University of Western Ontario, London, ON, Canada. 7. Department of Urological Sciences, University of British Columbia, Vancouver, BC, Canada. 8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. 9. Department of Urology, Landeskrankenhaus Weinviertel-Korneuburg, Korneuburg, Austria. 10. Department of Urology, Semmelweis University, Budapest, Hungary. 11. Department of Urology, Groupe Hospitalier Pitié - Salpêtrière, Assistance Publique Hopitaux de Paris, Faculty of Medicine Pierre et Marie Curie, Institut Universitaire de Cancérologie GRC5, University Paris 6, Paris, France. 12. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 13. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada. 14. Department of Urology, Urological Research Institute, San Raffaele Scientific Institute, Milan, Italy. 15. Department of Surgical, Oncological and Gastroenterologic Sciences, Urology Clinic, University of Padua, Padua, Italy. 16. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA.
Abstract
OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.
OBJECTIVE: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. PATIENTS AND METHODS: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. RESULTS: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. CONCLUSIONS: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.
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