Neoadjuvant Chemotherapy in Muscle Invasive Urothelial Bladder Cancer

  • Günter NiegischEmail author
  • Peter Albers


Efficacy of cisplatin-based neoadjuvant chemotherapy (NC) regarding improvement of cancer-specific outcomes in patients suffering from urothelial bladder carcinoma (UBC) has been shown in randomized trials and confirmed within three large metaanalyses. Accordingly, recent guidelines on treatment of UBC patients recommend the use of NC. Most frequently, a combination therapy with gemcitabine and cisplatin is used, despite prospective data comparing this regimen to cisplatin-based combinations used in the historical randomized trials. The ideal patient to undergo NC before radical cystectomy presents with a good performance status and renal function. Though outcome differences depending on tumor stage have not been shown in the meta-analyses and pre-cystectomy staging is often inadequate, ≥T3 N0 patients are those most likely to benefit from NC.


  1. 1.
    Madersbacher S, et al. Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003;21(4):690–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Hautmann RE, et al. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol. 2006;176(2):486–92. discussion 491-2.CrossRefPubMedGoogle Scholar
  3. 3.
    Hautmann RE, et al. Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol. 2012;61(5):1039–47.CrossRefPubMedGoogle Scholar
  4. 4.
    Miles BJ, et al. Referral and treatment rates of neoadjuvant chemotherapy in muscle-invasive bladder cancer before and after publication of a clinical practice guideline. Can Urol Assoc J. 2010;4(4):263–7.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    David KA, et al. Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base. J Urol. 2007;178(2):451–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Winquist E, et al. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004;171(2 Pt 1):561–9.CrossRefPubMedGoogle Scholar
  7. 7.
    ABC-Meta-analysis-Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005;48(2):202–5. discussion 205–6.CrossRefGoogle Scholar
  8. 8.
    ABC-Meta-analysis-Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361(9373):1927–34.CrossRefGoogle Scholar
  9. 9.
    Sherif A, et al. Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer—Nordic cystectomy trial 2. Scand J Urol Nephrol. 2002;36(6):419–25.CrossRefPubMedGoogle Scholar
  10. 10.
    Grossman HB, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.CrossRefPubMedGoogle Scholar
  11. 11.
    Malmstrom PU, et al. Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group. J Urol. 1996;155(6):1903–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Inernational-Collaboration-of-Trialists. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999;354(9178):533–40.CrossRefGoogle Scholar
  13. 13.
    International Collaboration of Trialists. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171–7.CrossRefPubMedCentralGoogle Scholar
  14. 14.
    Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, D.K., AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms. Langversion 1.1. 2016 [cited 2017 February 2017];
  15. 15.
    Milowsky MI, et al. 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. 2016;34(16):1945–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Alfred Witjes J, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71(3):462–75.CrossRefPubMedGoogle Scholar
  17. 17.
    National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management. 2015 [cited2017 February 21];
  18. 18.
    Dash A, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer. 2008;113(9):2471–7.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Zargar H, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2015;67(2):241–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Galsky MD, et al. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015;121(15):2586–93.CrossRefPubMedGoogle Scholar
  21. 21.
    Yin M, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016;21(6):708–15.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Johnson DC, et al. Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity. BJU Int. 2014;114(2):221–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Anderson EH. The associate degree program—a step to the baccalaureate degree in nursing. NLN Publ 1972;(15–1473):40–4.Google Scholar
  24. 24.
    Al-Daghmin A, et al. Efficacy of robot-assisted radical cystectomy (RARC) in advanced bladder cancer: results from the International Radical Cystectomy Consortium (IRCC). BJU Int. 2014;114(1):98–103.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Johar RS, et al. Complications after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol. 2013;64(1):52–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Dogliotti L, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007;52(1):134–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Galsky MD, et al. Treatment of patients with metastatic urothelial cancer “unfit” for Cisplatin-based chemotherapy. J Clin Oncol. 2011;29(17):2432–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Hussain SA, et al. A study of split-dose cisplatin-based neo-adjuvant chemotherapy in muscle-invasive bladder cancer. Oncol Lett. 2012;3(4):855–9.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Canter D, et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology. 2011;77(1):160–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Niegisch G, et al. Neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: which patients benefit? Eur Urol. 2013;64(3):355–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Koga F, et al. Favourable outcomes of patients with clinical stage T3N0M0 bladder cancer treated with induction low-dose chemo-radiotherapy plus partial or radical cystectomy vs immediate radical cystectomy: a single-institutional retrospective comparative study. BJU Int. 2009;104(2):189–94.CrossRefPubMedGoogle Scholar
  32. 32.
    Svatek RS, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort. BJU Int. 2011;107(6):898–904.CrossRefPubMedGoogle Scholar
  33. 33.
    Scosyrev E, et al. Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). BJU Int. 2011;108(5):693–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Wasco MJ, et al. Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection. Urology. 2007;70(1):69–74.CrossRefPubMedGoogle Scholar
  35. 35.
    Cheng L, et al. Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients. Cancer. 2004;101(5):957–62.CrossRefPubMedGoogle Scholar
  36. 36.
    Erdem GU, et al. Small cell carcinoma of the urinary bladder: changing trends in the current literature. Curr Med Res Opin. 2016;32(6):1013–21.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Urology, Medical FacultyHeinrich-Heine-UniversityDuesseldorfGermany

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