INTRODUCTION: Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes of neoadjuvant chemotherapy (NAC) in this population have never been explored. The objective of the study was to assess the impact of NAC on pathologic response and oncological outcomes stratified by age. PATIENTS AND METHODS: This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes. RESULTS: The cohorts' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly. CONCLUSION: Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal Canada

Department of Special Surgery Division of Urology Jordan University Hospital The University of Jordan Amman Jordan

Department of Urology Bichat Hospital Paris Descartes University Paris France

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology University Hospital Zurich Zurich Switzerland

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia; Department of Special Surgery Division of Urology Jordan University Hospital The University of Jordan Amman Jordan; Department of Urology Weill Cornell Medical College New York NY; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; European Association of Urology Research Foundation Arnhem The Netherlands

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Vienna Austria; Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Department of Urology IRCCS San Raffaele Hospital and Scientific Institute Milan Italy

Department of Urology Luzerner Kantonsspital Luzern Switzerland

Department of Urology Semmelweis University Budapest Hungary

Department of Urology University of Brescia Spedali Civili di Brescia Brescia Italy

Department of Urology University of Texas Southwestern Medical Center Dallas TX

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