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Neoadjuvant Chemotherapy in Elderly Patients With Upper Tract Urothelial Cancer: Oncologic Outcomes From a Multicenter Study

  • Nico C. Grossmann
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

    Department of Urology, University Hospital Zurich, Zurich, Switzerland
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  • Benjamin Pradere
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
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  • David D'Andrea
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
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  • Victor M. Schuettfort
    Affiliations
    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
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  • Keiichiro Mori
    Affiliations
    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
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  • Pawel Rajwa
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

    Department of Urology, Medical University of Silesia, Zabrze, Poland
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  • Fahad Quhal
    Affiliations
    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
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  • Ekaterina Laukhtina
    Affiliations
    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
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  • Satoshi Katayama
    Affiliations
    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
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  • Christian D. Fankhauser
    Affiliations
    Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland
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  • Evanguelos Xylinas
    Affiliations
    Department of Urology Bichat Hospital, Paris Descartes University, Paris, France
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  • Vitaly Margulis
    Affiliations
    Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX
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  • Marco Moschini
    Affiliations
    Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland
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  • Mohammad Abufaraj
    Affiliations
    Department of Special Surgery, Division of Urology, Jordan University Hospital, The University of Jordan, Amman, Jordan
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  • Marco Bandini
    Affiliations
    Department of Urology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy
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  • Chiara Lonati
    Affiliations
    Department of Urology, University of Brescia, Spedali Civili di Brescia, Brescia, Italy
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  • Peter Nyirady
    Affiliations
    Department of Urology, Semmelweis University, Budapest, Hungary
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  • Pierre I. Karakiewicz
    Affiliations
    Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada
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  • Harun Fajkovic
    Affiliations
    Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

    Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria
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  • Shahrokh F. Shariat
    Correspondence
    Address for correspondence: Shahrokh F. Shariat, MD, PhD, Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
    Affiliations
    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, Second 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
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Published:January 11, 2022DOI:https://doi.org/10.1016/j.clgc.2022.01.004

      Highlights

      • Fit elderly patients with high-risk UTUC may benefit equally from NAC and RNU as their younger counterparts
      • Cisplatin-based chemotherapy results in the highest pathologic response rates across both age groups
      • Elderly, cisplatin-ineligible patients, experienced the worst response rates after non-cisplantin-based NAC and might therefore benefit rather from immediate RNU

      Abstract

      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.

      Keywords

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