Advertisement

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

  • Sebastiano Nazzani
  • Felix Preisser
  • Elio Mazzone
  • Zhe Tian
  • Francesco A. Mistretta
  • Shahrokh F. Shariat
  • Denis Soulières
  • Fred Saad
  • Emanuele Montanari
  • Stefano Luzzago
  • Alberto Briganti
  • Luca Carmignani
  • Pierre I. Karakiewicz
Original Article
  • 36 Downloads

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.

Keywords

Upper urinary tract Urothelial carcinoma Positive lymph nodes SEER Chemotherapy 

Notes

Author 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.

Funding

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

Compliance with ethical standards

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.

Ethical standards

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.

Supplementary material

345_2018_2516_MOESM1_ESM.docx (28 kb)
Graphical representation of the effect of inverse probability after treatment weighting on baseline characteristics. (DOCX 28 kb)
345_2018_2516_MOESM2_ESM.docx (21 kb)
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)

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics. CA Cancer J Clin 68:7–30.  https://doi.org/10.3322/caac.21442 CrossRefPubMedGoogle Scholar
  2. 2.
    Browne BM, Stensland KD, Moynihan MJ, Canes D (2018) An analysis of staging and treatment trends for upper tract urothelial carcinoma in the national cancer database. Clin Genitourin Cancer.  https://doi.org/10.1016/j.clgc.2018.01.015 CrossRefPubMedGoogle Scholar
  3. 3.
    Professionals S-O. Upper Urinary Tract Urothelial Cell Carcinoma. Uroweb n.d. http://uroweb.org/guideline/upper-urinary-tract-urothelial-cell-carcinoma/ (accessed May 11, 2018)
  4. 4.
    Clark PE, Hoimes C, Patterson A (2017) NCCN guidelines index table of contents discussion. Bladder Cancer 2017:92Google Scholar
  5. 5.
    Milowsky MI, Rumble RB, Booth CM, Gilligan T, Eapen LJ, Hauke RJ et al (2016) Guideline on muscle-invasive and metastatic bladder cancer (European association of urology guideline): American society of clinical oncology clinical practice guideline endorsement. J Clin Oncol 34:1945–1952.  https://doi.org/10.1200/JCO.2015.65.9797 CrossRefPubMedGoogle Scholar
  6. 6.
    Leow JJ, Martin-Doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT et al (2014) Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 66:42–54.  https://doi.org/10.1016/j.eururo.2013.08.033 CrossRefPubMedGoogle Scholar
  7. 7.
    Leow JJ, Chong KT, Chang SL, Bellmunt J (2016) Upper tract urothelial carcinoma: a different disease entity in terms of management. ESMO Open 1:e000126.  https://doi.org/10.1136/esmoopen-2016-000126 CrossRefPubMedGoogle Scholar
  8. 8.
    Birtle AJ, Chester JD, Jones RJ, Johnson M, Hill M, Bryan RT et al (2018) Results of POUT: a phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC). J Clin Oncol 36:407–407.  https://doi.org/10.1200/JCO.2018.36.6_suppl.407 CrossRefGoogle Scholar
  9. 9.
    Seisen T, Krasnow RE, Bellmunt J, Rouprêt M, Leow JJ, Lipsitz SR et al (2017) Effectiveness of adjuvant chemotherapy after radical nephroureterectomy for locally advanced and/or positive regional lymph node upper tract urothelial carcinoma. J Clin Oncol 35:852–860.  https://doi.org/10.1200/JCO.2016.69.4141 CrossRefPubMedGoogle Scholar
  10. 10.
    Kwak C, Lee SE, Jeong IG, Ku JH (2006) Adjuvant systemic chemotherapy in the treatment of patients with invasive transitional cell carcinoma of the upper urinary tract. Urology 68:53–57.  https://doi.org/10.1016/j.urology.2006.01.053 CrossRefPubMedGoogle Scholar
  11. 11.
    Suzuki S, Shinohara N, Harabayashi T, Sato S, Abe T, Koyanagi T (2004) Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer. Int J Urol 11:456–460.  https://doi.org/10.1111/j.1442-2042.2004.00841.x CrossRefPubMedGoogle Scholar
  12. 12.
    Soga N, Arima K, Sugimura Y (2008) Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma. Int J Urol Off J Jpn Urol Assoc 15:800–803.  https://doi.org/10.1111/j.1442-2042.2008.02114.x CrossRefGoogle Scholar
  13. 13.
    Leow JJ, Martin-Doyle W, Fay AP, Choueiri TK, Chang SL, Bellmunt J (2014) A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol 66:529–541.  https://doi.org/10.1016/j.eururo.2014.03.003 CrossRefPubMedGoogle Scholar
  14. 14.
    Vassilakopoulou M, de la Motte Rouge T, Colin P, Ouzzane A, Khayat D, Dimopoulos M-A et al (2011) Outcomes after adjuvant chemotherapy in the treatment of high-risk urothelial carcinoma of the upper urinary tract (UUT-UC): results from a large multicenter collaborative study. Cancer 117:5500–5508.  https://doi.org/10.1002/cncr.26172 CrossRefPubMedGoogle Scholar
  15. 15.
    Yafi FA, Tanguay S, Rendon R, Jacobsen N, Fairey A, Izawa J et al (2014) Adjuvant chemotherapy for upper-tract urothelial carcinoma treated with nephroureterectomy: assessment of adequate renal function and influence on outcome. Urol Oncol 32(31):e17–e24.  https://doi.org/10.1016/j.urolonc.2012.11.014 CrossRefGoogle Scholar
  16. 16.
    Necchi A, Vullo SL, Mariani L, Moschini M, Hendricksen K, Rink M et al (2018) Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma: a joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration. BJU Int 121:252–259.  https://doi.org/10.1111/bju.14020 CrossRefPubMedGoogle Scholar
  17. 17.
    Nazzani S, Bandini M, Marchioni M, Preisser F, Tian Z, Soulières D et al (2018) A contemporary analysis of radiotherapy effect in surgically treated retroperitoneal sarcoma. Radiother Oncol J Eur Soc Ther Radiol Oncol.  https://doi.org/10.1016/j.radonc.2018.03.027 CrossRefGoogle Scholar
  18. 18.
    Marchioni M, Bandini M, Preisser F, Tian Z, Kapoor A, Cindolo L et al (2017) Survival after Cytoreductive Nephrectomy in Metastatic Non-clear Cell Renal Cell Carcinoma Patients: A Population-based Study. Eur Urol Focus.  https://doi.org/10.1016/j.euf.2017.11.012 CrossRefPubMedGoogle Scholar
  19. 19.
    Nazzani S, Preisser F, Mazzone E, Tian Z, Mistretta FA, Shariat SF et al (2018) In-hospital length of stay after major oncological surgical procedures. Eur J Surg Oncol.  https://doi.org/10.1016/j.ejso.2018.05.001 CrossRefPubMedGoogle Scholar
  20. 20.
    Hoffman-Censits J, Puligandla M, Trabulsi E, Plimack E, Kessler E, Matin SF et al (2018) LBA26 PHASE II TRIAL OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY EXTIRPATIVE SURGERY FOR PATIENTS WITH HIGH GRADE UPPER TRACT UROTHELIAL CARCINOMA (HG UTUC): RESULTS FROM ECOG-ACRIN 8141. J Urol 199:e1166–e1167.  https://doi.org/10.1016/j.juro.2018.03.098 CrossRefGoogle Scholar
  21. 21.
    Liao RS, Gupta M, Schwen ZR, Patel HD, Kates M, Johnson MH et al (2018) Comparison of pathological stage in patients treated with and without neoadjuvant chemotherapy for high risk upper tract urothelial carcinoma. J Urol 200:68–73.  https://doi.org/10.1016/j.juro.2017.12.054 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sebastiano Nazzani
    • 1
    • 2
    • 3
  • Felix Preisser
    • 1
    • 2
    • 5
  • Elio Mazzone
    • 1
    • 2
    • 4
  • Zhe Tian
    • 2
  • Francesco A. Mistretta
    • 6
  • Shahrokh F. Shariat
    • 7
  • Denis Soulières
    • 2
  • Fred Saad
    • 2
  • Emanuele Montanari
    • 8
  • Stefano Luzzago
    • 8
  • Alberto Briganti
    • 4
  • Luca Carmignani
    • 3
  • Pierre I. Karakiewicz
    • 1
    • 2
  1. 1.Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health CenterMontrealCanada
  2. 2.Centre de recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM) and Institut du cancer de MontréalMontréalCanada
  3. 3.Academic Department of UrologyIRCCS Policlinico San Donato, University of MilanMilano MIItaly
  4. 4.Division of Oncology/Unit of UrologyURI, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele UniversityMilanItaly
  5. 5.Martini-Klinik Prostate Cancer CenterUniversity Hospital Hamburg-EppendorfHamburgGermany
  6. 6.Department of UrologyIstituto Europeo di OncologiaMilanItaly
  7. 7.Department of UrologyMedical University of ViennaViennaAustria
  8. 8.Department of UrologyIRCCS Fondazione Ca’ Granda-Ospedale Maggiore Policlinico University of MilanMilanItaly

Personalised recommendations