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Bladder preservation treatment options for muscle-invasive urothelial bladder cancer

Jason A Efstathiou, MD, DPhil
Philip Saylor, MD
Matthew Wszolek, MD
Nicholas J Giacalone, MD
Section Editors
Seth P Lerner, MD
Derek Raghavan, MD, PhD, FACP, FASCO
Deputy Editor
Michael E Ross, MD


Bladder cancer is the most common malignancy of the urinary system, with an estimated 74,000 new cases and 16,000 deaths in the United States annually [1]. Worldwide, bladder cancer accounts for approximately 450,000 new cases and 165,000 deaths [2]. In developed areas of the world, such as North America and Western Europe, these bladder cancers are predominantly urothelial.

Nearly 70 percent of new bladder cancer diagnoses are early-stage (ie, Ta, Tis, and T1 disease (table 1)) and have not yet invaded the muscular layer of the bladder wall. These patients are often managed with transurethral resection of bladder tumor (TURBT) with or without adjuvant intravesical therapy. The remaining 30 percent of patients have muscle-invasive bladder cancer, including cancer involving the muscularis propria (T2), perivesical tissue (T3), or adjacent pelvic organs/structures (T4).

Radical cystectomy remains the cornerstone of curative treatment for muscle-invasive bladder cancer. Radical cystectomy involves removal of the bladder (in combination with removal of the uterus/ovaries/fallopian tubes and possibly a portion of the vagina in women, and the prostate and seminal vesicles in men), pelvic lymph node dissection, and reconstruction of the urinary tract. The morbidity and long-term outcomes of cystectomy are well documented [3].

Because of the high risk of distant failure in muscle-invasive bladder cancer, systemic chemotherapy either before or after radical cystectomy is often recommended to improve outcomes. Modern series of patients managed with radical cystectomy have a five-year pelvic control rate of nearly 80 percent and five-year overall survival rates ranging from 40 to 60 percent [4,5].

Modern oncologic therapies are increasingly driven towards organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Combined-modality therapy (CMT) incorporating maximal TURBT followed by radiation therapy with concurrent radiosensitizing chemotherapy can be a comparably effective regimen to preserve a functioning bladder in well-selected patients who are either poor candidates for radical cystectomy or patients who are motivated to maintain their native bladder.


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Literature review current through: Sep 2016. | This topic last updated: Oct 27, 2015.
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  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
  2. Sauter G. Bladder Cancer. In: World Cancer Report 2014, Stewart BW, Wild CP. (Eds), International Agency for Research on Cancer, Lyon 2014. p.445.
  3. Donat SM, Shabsigh A, Savage C, et al. Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a high-volume tertiary cancer center experience. Eur Urol 2009; 55:177.
  4. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349:859.
  5. Zehnder P, Studer UE, Skinner EC, et al. Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J Urol 2011; 186:1261.
  6. Nishimura K, Hida S, Nishio Y, et al. The validity of magnetic resonance imaging (MRI) in the staging of bladder cancer: comparison with computed tomography (CT) and transurethral ultrasonography (US). Jpn J Clin Oncol 1988; 18:217.
  7. Mallampati GK, Siegelman ES. MR imaging of the bladder. Magn Reson Imaging Clin N Am 2004; 12:545.
  8. Tekes A, Kamel I, Imam K, et al. Dynamic MRI of bladder cancer: evaluation of staging accuracy. AJR Am J Roentgenol 2005; 184:121.
  9. Voges GE, Tauschke E, Stöckle M, et al. Computerized tomography: an unreliable method for accurate staging of bladder tumors in patients who are candidates for radical cystectomy. J Urol 1989; 142:972.
  10. Kim B, Semelka RC, Ascher SM, et al. Bladder tumor staging: comparison of contrast-enhanced CT, T1- and T2-weighted MR imaging, dynamic gadolinium-enhanced imaging, and late gadolinium-enhanced imaging. Radiology 1994; 193:239.
  11. Green DA, Durand M, Gumpeni N, et al. Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques. BJU Int 2012; 110:1463.
  12. National Comprehensive Cancer Network guidelins http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site (Accessed on July 07, 2015).
  13. Huddart RA, Hall E, Lewis R, et al. Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010; 106:753.
  14. Gray PJ, Lin CC, Jemal A, et al. Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the national cancer data base. Int J Radiat Oncol Biol Phys 2014; 88:1048.
  15. Herr HW. Conservative management of muscle-infiltrating bladder cancer: prospective experience. J Urol 1987; 138:1162.
  16. Pos F, Horenblas S, Dom P, et al. Organ preservation in invasive bladder cancer: brachytherapy, an alternative to cystectomy and combined modality treatment? Int J Radiat Oncol Biol Phys 2005; 61:678.
  17. Kassouf W, Swanson D, Kamat AM, et al. Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience. J Urol 2006; 175:2058.
  18. Eapen L, Stewart D, Collins J, Peterson R. Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol 2004; 172:1276.
  19. Scosyrev E, Noyes K, Feng C, Messing E. Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer 2009; 115:68.
  20. Liberman D, Lughezzani G, Sun M, et al. Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder. Urology 2011; 77:660.
  21. Arslan B, Bozkurt IH, Yonguc T, et al. Clinical features and outcomes of nontransitional cell carcinomas of the urinary bladder: Analysis of 125 cases. Urol Ann 2015; 7:177.
  22. Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol 2012; 61:705.
  23. Perdonà S, Autorino R, Damiano R, et al. Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: a multi-institutional, long-term experience. Cancer 2008; 112:75.
  24. Rödel C, Grabenbauer GG, Kühn R, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002; 20:3061.
  25. Zapatero A, Martin de Vidales C, Arellano R, et al. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol 2010; 28:368.
  26. Shipley WU, Winter KA, Kaufman DS, et al. 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; 16:3576.
  27. James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012; 366:1477.
  28. Fung CY, Shipley WU, Young RH, et al. Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy. J Clin Oncol 1991; 9:1533.
  29. Ploussard G, Daneshmand S, Efstathiou JA, et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol 2014; 66:120.
  30. Clayman RH, Shipley WU, Galland-Girodet S, et al. Outcomes of Selective Bladder Preservation in the Elderly Treated With Conservative Surgery and Chemoradiation. Int J Radiat Oncol Biol Phys 2013; 87:S83.
  31. Mak RH, Hunt D, Shipley WU, et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 2014; 32:3801.
  32. Duncan W, Quilty PM. The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. Radiother Oncol 1986; 7:299.
  33. Smaaland R, Akslen LA, Tønder B, et al. Radical radiation treatment of invasive and locally advanced bladder carcinoma in elderly patients. Br J Urol 1991; 67:61.
  34. Pollack A, Zagars GK, Swanson DA. Muscle-invasive bladder cancer treated with external beam radiotherapy: prognostic factors. Int J Radiat Oncol Biol Phys 1994; 30:267.
  35. Laurberg JR, Brems-Eskildsen AS, Nordentoft I, et al. Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 2012; 110:E1228.
  36. Coppin CM, Gospodarowicz MK, James K, 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; 14:2901.
  37. Choudhury A, Swindell R, Logue JP, et al. Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol 2011; 29:733.
  38. Kent E, Sandler H, Montie J, et al. Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial. J Clin Oncol 2004; 22:2540.
  39. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol 2010; 28:4912.
  40. International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, et al. 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; 29:2171.
  41. Hagan MP, Winter KA, Kaufman DS, et al. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys 2003; 57:665.
  42. Kaufman DS, Winter KA, Shipley WU, et al. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology 2009; 73:833.
  43. Mitin T, Hunt D, Shipley WU, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol 2013; 14:863.
  44. Weiss C, Wittlinger M, Engehausen DG, et al. Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy. Int J Radiat Oncol Biol Phys 2008; 70:1502.
  45. Zietman AL, Grocela J, Zehr E, et al. Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder. Urology 2001; 58:380.
  46. Sanchez A, Wszolek MF, Clayman RH, et al. Incidence and Management of Non-muscle Invasive Bladder Cancer Recurrences After Complete Response to Combined-Modality Organ-Preserving Therapy for Muscle Invasive Bladder Cancer. J Urol 2015; 193:e298.
  47. Eswara JR, Efstathiou JA, Heney NM, et al. Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. J Urol 2012; 187:463.
  48. Ramani VA, Maddineni SB, Grey BR, Clarke NW. Differential complication rates following radical cystectomy in the irradiated and nonirradiated pelvis. Eur Urol 2010; 57:1058.
  49. Efstathiou JA, Bae K, Shipley WU, et al. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 2009; 27:4055.
  50. Zietman AL, Sacco D, Skowronski U, et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J Urol 2003; 170:1772.
  51. Mak KS, Smith A, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. J Clin Oncol 2015 33: (suppl 7; abstr 319).
  52. National Comprehensive Cancer Network, “National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Bladder Cancer.” 2015.
  53. Bladder cancer: diagnosis and management. 1-recommendations. Guidance and guidelines. NICE. http://www.nice.org.uk/guidance/ng2/chapter/1-recommendations#treating-muscle-invasive-bladder-cancer-2 (Accessed on June 14, 2015).
  54. 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.
  55. Bladder Cancer - Muscle invasive and metastatic. Uroweb. http://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/ (Accessed on June 14, 2015).
  56. Find Answers – BCAN. Bladder Cancer Advocacy Network - BCAN. http://www.bcan.org/learn/. Accessed: 15-Jun-2015.