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Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract

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Abstract

Objectives

To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma.

Methods

Within the Surveillance, Epidemiology, and End Results database (2004–2014), we identified 1286 patients with T3 or T4, N 0–3 M0 UTUC. Kaplan–Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI).

Results

Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58–0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48–0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52–1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses.

Conclusions

Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3–T4, N1–N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada

    Sebastiano Nazzani, Felix Preisser, Elio Mazzone & Pierre I. Karakiewicz

  2. Centre de recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montréal, QC, Canada

    Sebastiano Nazzani, Felix Preisser, Elio Mazzone, Zhe Tian, Denis Soulières, Fred Saad & Pierre I. Karakiewicz

  3. Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Corso San Gottardo 12, Milano MI, Italy

    Sebastiano Nazzani & Luca Carmignani

  4. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy

    Elio Mazzone & Alberto Briganti

  5. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Felix Preisser

  6. Department of Urology, Istituto Europeo di Oncologia, Milan, Italy

    Francesco A. Mistretta

  7. Department of Urology, Medical University of Vienna, Vienna, Austria

    Shahrokh F. Shariat

  8. Department of Urology, IRCCS Fondazione Ca’ Granda-Ospedale Maggiore Policlinico University of Milan, Milan, Italy

    Emanuele Montanari & Stefano Luzzago

Authors
  1. Sebastiano Nazzani
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  2. Felix Preisser
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Contributions

Protocol/project development: SN, FP, EM, PIK. Data collection or management: SN, FP, EM, PIK, ZT. Data analysis: SN, FP, EM, PIK, ZT. Manuscript writing/editing: SN, FAM, SFS, DS, FS, EM, SL, AB, LC and PIK.

Corresponding author

Correspondence to Sebastiano Nazzani.

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Financial disclosures

Sebastiano Nazzani certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none.

Conflict of interest

The authors declare that they have no competing interests.

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We affirm that all authors have complied with the principles of the World Journal of Urology regarding ethical responsibilities of authors and compliance with ethical standards.

Electronic supplementary material

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345_2018_2516_MOESM1_ESM.docx

Graphical representation of the effect of inverse probability after treatment weighting on baseline characteristics. (DOCX 28 kb)

345_2018_2516_MOESM2_ESM.docx

Multivariable Cox regression models predicting overall mortality in 1286 surgically treated non-metastatic upper urinary tract urothelial carcinoma patients (Adjusted for tumor grade, tumor location, laterality, race, gender and year of diagnosis). (DOCX 20 kb)

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Nazzani, S., Preisser, F., Mazzone, E. et al. Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract. World J Urol 37, 1329–1337 (2019). https://doi.org/10.1007/s00345-018-2516-z

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  • DOI: https://doi.org/10.1007/s00345-018-2516-z

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