Skip to main content

Systemic Therapy for Bladder Cancer

  • 1034 Accesses

Abstract

The gold standard of muscle-invasive bladder cancer is radical cystectomy. Before surgery three cycles of neoadjuvant chemotherapy can improve the overall survival and decrease the risk of recurrence. For operated high-risk without neoadjuvant therapy patients, adjuvant chemotherapy can be a good option. The primary treatment of metastatic bladder cancer is cisplatin-based chemotherapy. However, even though it is considered sensitive to chemotherapy, the average survival is 15 months and even less if there is an organ metastasis. For these patients 5-year survival rate is 5–20%. Several studies have shown different mutations in muscle-invasive bladder cancer. These mutations are being studied as a targeted therapy option for cases where chemotherapy is not sufficient. Although there is not a specifically approved treatment model for metastatic bladder cancer, targeted therapy is becoming a significant choice. According to the mutation analysis of the Cancer Genome Atlas (TCGA) project, there are three major pathway abnormalities in metastatic bladder cancer: regulation of cell cycle, RTK/RAS/PIK3, and chromatin abnormalities. The studies about the treatment of bladder cancers with cell cycle regulators, mTOR inhibitors, and EGFR inhibitors will be highly important in the future. Immunotherapy with the checkpoint inhibitors (an anti-PD1 therapy with atezolizumab , durvalumab) improves survival.

Keywords

  • Chemotherapy
  • Bladder cancer
  • Adjuvant chemotherapy

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-319-56114-1_5
  • Chapter length: 7 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   139.00
Price excludes VAT (USA)
  • ISBN: 978-3-319-56114-1
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   179.99
Price excludes VAT (USA)
Hardcover Book
USD   179.99
Price excludes VAT (USA)

References

  1. Vale C. Advanced bladder cancer meta-analysis collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361(9373):1927–34.

    CAS  CrossRef  Google Scholar 

  2. Witjes JA, et al. Muscle-invasive and metastatic bladder cancer. EAU guidelines. 2013.

    Google Scholar 

  3. Gakis G, Efstathiou J, Lerner SP, et al. ICUD-EAU international consultation on bladder cancer 2012: radical cystectomy and bladder preservation for muscle- invasive urothelial carcinoma of the bladder. Eur Urol. 2013;63:45–57.

    CrossRef  PubMed  Google Scholar 

  4. Stein S, John P, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19(3):666–75.

    CAS  CrossRef  PubMed  Google Scholar 

  5. Coppin CM, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1996;14(11):2901–7.

    CAS  CrossRef  PubMed  Google Scholar 

  6. Leow JJ, Martin-Doyle W, Rajagopal PS, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2014;66:42–54.

    CAS  CrossRef  PubMed  Google Scholar 

  7. Bellmunt J, Orsola A, Leow JJ, Wiegel T, De Santis M, Horwich A. On behalf of the ESMO Guidelines Working Group. 2014

    Google Scholar 

  8. Milosevic M, Gospodarowicz M, Zietman A, et al. Radiotherapy for bladder cancer. Urology. 2007;69:80–92.

    CrossRef  PubMed  Google Scholar 

  9. Schultz PK, et al. Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up. J Clin Oncol. 1994;12(7):1394–401.

    CAS  CrossRef  PubMed  Google Scholar 

  10. Madersbacher S, et al. Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003;21(4):690–6.

    CrossRef  PubMed  Google Scholar 

  11. Chedgy EC, et al. Using the neoadjuvant chemotherapy paradigm to develop precision therapy for muscle-invasive bladder cancer. Urol Oncol Semin Orig Invest. 2016;34(10):469–76.

    Google Scholar 

  12. Sonpavde G, et al. Chemotherapy for muscle-invasive bladder cancer: better late than never? J Clin Oncol. 2016:JCO654442.

    Google Scholar 

  13. Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2015;67:241–9.

    CrossRef  PubMed  Google Scholar 

  14. Shipley WU, et al. An update of combined modality therapy for patients with muscle invading bladder cancer using selective bladder preservation or cystectomy. J Urol. 1999;162(2):445–50.

    CAS  CrossRef  PubMed  Google Scholar 

  15. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Doggett RS. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998;16(11):3576–83.

    CAS  CrossRef  PubMed  Google Scholar 

  16. William T, et al. Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. Int J Radiat Oncol Biol Phys. 1993;25(5):783–90.

    CrossRef  Google Scholar 

  17. Herr HW, Dotan Z, Donat SM, Bajorin DF. Defining optimal therapy for muscle invasive bladder cancer. J Urol. 2007;177(2):437–43.

    CAS  CrossRef  PubMed  Google Scholar 

  18. Kachnic LA, et al. Bladder preservation by combined modality therapy for invasive bladder cancer. J Clin Oncol. 1997;15(3):1022–9.

    CAS  CrossRef  PubMed  Google Scholar 

  19. Balar A, Bajorin DF, Milowsky MI. Management of invasive bladder cancer in patients who are not candidates for or decline cystectomy. Ther Adv Urol. 2011;3(3):107–17.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  20. James ND, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366(16):1477–88.

    CAS  CrossRef  PubMed  Google Scholar 

  21. Witjes JA, Compérat E, Cowan NC, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 Guidelines. Eur Urol. 2014;65:778–92.

    CrossRef  PubMed  Google Scholar 

  22. Von der Maase H, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–77.

    CrossRef  PubMed  Google Scholar 

  23. Von der Maase H, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8.

    CrossRef  PubMed  Google Scholar 

  24. Bellmunt J, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012;30(10):1107–13.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  25. Garcia JA, Dreicer R. Systemic chemotherapy for advanced bladder cancer: update and controversies. J Clin Oncol. 2006;24(35):5545–51.

    CAS  CrossRef  PubMed  Google Scholar 

  26. The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507:315–22.

    CrossRef  PubMed Central  Google Scholar 

  27. Lerner SP. Targeted therapies for metastatic bladder cancer. J Urol. 2015;193:8–9.

    CrossRef  PubMed  Google Scholar 

  28. Iyer G, Al-Ahmadie H, Schultz N, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31(25):3133–40.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  29. Zho Z, Shen Z, Xu C. Targeted therapy for advanced urothelial cancer of the bladder: where do we stand? Anticancer Agents Med Chem. 2012;12(9):1081–7.

    CrossRef  Google Scholar 

  30. McDermott DF, et al. Atezolizumab, an anti–programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol. 2016;34(8):833–42.

    CAS  CrossRef  PubMed  Google Scholar 

  31. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10030):1909–20.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  32. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558–62.

    CAS  CrossRef  PubMed  Google Scholar 

  33. Agarwal N, Bellmunt J, Maughan BL, et al. Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma. Clin Genitourin Cancer. 2014;12(2):130–7.

    CrossRef  PubMed  Google Scholar 

  34. Yadav M, Jhunjhunwala S, Phung QT, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515(7528):572–6.

    CAS  CrossRef  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nil Molinas Mandel M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Mandel, N.M., Mandel, S. (2017). Systemic Therapy for Bladder Cancer. In: Ozyigit, G., Selek, U. (eds) Principles and Practice of Urooncology. Springer, Cham. https://doi.org/10.1007/978-3-319-56114-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-56114-1_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56113-4

  • Online ISBN: 978-3-319-56114-1

  • eBook Packages: MedicineMedicine (R0)