Bladder preservation in the treatment of muscle-invasive bladder cancer

Main Article Content

Kris Prado
Kiran Gollapudi
Christopher King
Michael L Steinberg
Arnold I Chin


bladder cancer, trimodality therapy, bladder preservation


Organ preserving strategies are being increasingly utilized in the treatment of solid malignancies with the intent of reducing surgical morbidity and maintaining quality of life. Organ preservation becomes a viable approach only when cancer outcomes are not compromised when compared to radical resection. We reviewed the current literature on bladder preservation for muscle-invasive bladder cancer, focusing on trimodality therapy consisting of complete transurethral resection, radiation therapy, and chemotherapy. Acknowledging the absence of randomized clinical trials, differences in patient selection, and variation in study protocols, trimodality therapy may yield similar 5- and 10-year overall survival rates compared to radical cystectomy alone. This includes the approximately 30% of patients who enter a bladder preservation protocol and undergo salvage radical cystectomy for failure of local control. Currently, bladder preservation appears to be an alternative to radical cystectomy in select patients who have appropriate rigorous surveillance.


Metrics Loading ...
Abstract 62 | HTML Downloads 22 PDF Downloads 23


1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63: 11-30.

2. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, et al. (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19: 666-675.

3. Dalbagni G, Genega E, Hashibe M, Zhang ZF, Russo P, et al. (2001) Cystectomy for bladder cancer: a contemporary series. J Urol 165: 1111-1116.

4. Madersbacher S, Hochreiter W, Burkhard F, Thalmann G, Danuser H, et al. (2003) Radical cystectomy for bladder cancer today--a homogeneous series without neoadjuvant therapy. J Clin Oncol 21: 690-696.

5. Hautmann RE, de Petriconi RC, Pfeiffer C, Volkmer BG (2012) Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 61: 1039-1047.

6. Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, et al. (2006) Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 176: 2414-2422; discussion 2422.

7. Manoharan M, Ayyathurai R, Soloway MS (2009) Radical cystectomy for urothelial carcinoma of the bladder: an analysis of perioperative and survival outcome. BJU Int 104: 1227-1232.

8. Advanced Bladder Cancer Meta-analysis C (2005) 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 48: 202-205; discussion 205-206.

9. Jenkins BJ, Caulfield MJ, Fowler CG, Badenoch DF, Tiptaft RC, et al. (1988) Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer. Br J Urol 62: 343-346.

10. Gospodarowicz MK, Rider WD, Keen CW, Connolly JG, Jewett MA, et al. (1991) Bladder cancer: long-term follow-up results of patients treated with radical radiation. Clin Oncol (R Coll Radiol) 3: 155-161.

11. Fossa SD, Waehre H, Aass N, Jacobsen AB, Olsen DR, et al. (1993) Bladder cancer definitive radiation therapy of muscle-invasive bladder cancer. A retrospective analysis of 317 patients. Cancer 72: 3036-3043.
12. Mameghan H, Fisher R, Mameghan J, Brook S (1995) Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder. Int J Radiat Oncol Biol Phys 31: 247-254.

13. Horwich A, Dearnaley D, Huddart R, Graham J, Bessell E, et al. (2005) A randomised trial of accelerated radiotherapy for localised invasive bladder cancer. Radiother Oncol 75: 34-43.

14. Coppin CM, Gospodarowicz MK, James K, Tannock IF, Zee B, et al. (1996) 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 14: 2901-2907.

15. Chung PW, Bristow RG, Milosevic MF, Yi QL, Jewett MA, et al. (2007) Long-term outcome of radiation-based conservation therapy for invasive bladder cancer. Urol Oncol 25: 303-309.

16. Holzbeierlein JM, Lopez-Corona E, Bochner BH, Herr HW, Donat SM, et al. (2004) Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection. J Urol 172: 878-881.

17. Kassouf W, Swanson D, Kamat AM, Leibovici D, Siefker-Radtke A, et al. (2006) Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience. J Urol 175: 2058-2062.

18. Smaldone MC, Jacobs BL, Smaldone AM, Hrebinko RL, Jr. (2008) Long-term results of selective partial cystectomy for invasive urothelial bladder carcinoma. Urology 72: 613-616.

19. Solsona E, Iborra I, Ricos JV, Monros JL, Casanova J, et al. (1998) Feasibility of transurethral resection for muscle infiltrating carcinoma of the bladder: long-term followup of a prospective study. J Urol 159: 95-98; discussion 98-99.

20. Herr HW (2001) Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol 19: 89-93.

21. Solsona E, Climent MA, Iborra I, Collado A, Rubio J, et al. (2009) Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy. Eur Urol 55: 911-919.

22. Shipley WU, Rose MA, Perrone TL, Mannix CM, Heney NM, et al. (1985) Full-dose irradiation for patients with invasive bladder carcinoma: clinical and histological factors prognostic of improved survival. J Urol 134: 679-683

23. James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, et al. (2012) Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder Cancer. N Engl J Med 16 1477-1488.

24. Tunio MA, Hashmi A, Qayyum A, Mohsin R, Zaeem A (2012) Whole-pelvis or bladder-only chemoradiation for lymph node-negative invasive bladder cancer: single-institution experience. Int J Radiat Oncol Biol Phys 82: e457-462.

25. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, et al. (1998) 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 16: 3576-3583.

26. Housset M, Maulard C, Chretien Y, Dufour B, Delanian S, et al. (1993) Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study. J Clin Oncol 11: 2150-2157.

27. Efstathiou JA, Spiegel DY, Shipley WU, Heney NM, Kaufman DS, et al. (2012) Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol 61: 705-711.

28. Rodel C, Grabenbauer GG, Kuhn R, Papadopoulos T, Dunst J, et al. (2002) Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 20: 3061-3071.

29. Weiss C, Engehausen DG, Krause FS, Papadopoulos T, Dunst J, et al. (2007) Radiochemotherapy with cisplatin and 5-fluorouracil after transurethral surgery in patients with bladder cancer. Int J Radiat Oncol Biol Phys 68: 1072-1080.

30. Krause FS, Walter B, Ott OJ, Haberle L, Weiss C, et al. (2011) 15-year survival rates after transurethral resection and radiochemotherapy or radiation in bladder cancer treatment. Anticancer Res 31: 985-990.

31. Tester W, Porter A, Asbell S, Coughlin C, Heaney J, et al. (1993) Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. Int J Radiat Oncol Biol Phys 25: 783-790.

32. Tester W, Caplan R, Heaney J, Venner P, Whittington R, et al. (1996) Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol 14: 119-126.

33. Arias F, Dominguez MA, Martinez E, Illarramendi JJ, Miquelez S, et al. (2000) Chemoradiotherapy for muscle invading bladder carcinoma. Final report of a single institutional organ-sparing program. Int J Radiat Oncol Biol Phys 47: 373-378.
34. Kaufman DS, Winter KA, Shipley WU, Heney NM, Chetner MP, et al. (2000) The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist 5: 471-476.

35. Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, et al. (2003) 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 57: 665-672.

36. Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ, 3rd, et al. (2009) 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 73: 833-837.

37. Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, et al. (2013) Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracilcisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol 14: 863–872.

38. Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, et al. (2009) 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 27: 4055-4061.

39. Wright JL, Porter MP (2007) Quality-of-life assessment in patients with bladder cancer. Nat Clin Pract Urol 4: 147-154.

40. Allareddy V, Kennedy J, West MM, Konety BR (2006) Quality of life in long-term survivors of bladder cancer. Cancer 106: 2355-2362.

41. Gilbert SM, Wood DP, Dunn RL, Weizer AZ, Lee CT, et al. (2007) Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI). Cancer 109: 1756-1762.

42. Hart S, Skinner EC, Meyerowitz BE, Boyd S, Lieskovsky G, et al. (1999) Quality of life after radical cystectomy for bladder cancer in patients with an ileal conduit, cutaneous or urethral kock pouch. J Urol 162: 77-81.

43. Mottet N, Castagnola C, Rischmann P, Deixonne M, Guyot M, et al. (2008) [Quality of life after cystectomy: French national survey conducted by the French Association of Urology (AFU), the French Federation of Stoma Patients (FSF) and the French Association of Enterostomy Patients (AFET) in patients with ileal conduit urinary diversion or orthotopic neobladder]. Prog Urol 18: 292-298.

44. Henningsohn L, Steven K, Kallestrup EB, Steineck G (2002) Distressful symptoms and well-being after radical cystectomy and orthotopic bladder substitution compared with a matched control population. J Urol 168: 168-174; discussion 174-165.

45. Zietman AL, Sacco D, Skowronski U, Gomery P, Kaufman DS, et al. (2003) 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 170: 1772-1776.

46. Fellin G, Graffer U, Bolner A, Ambrosini G, Caffo O, et al. (1997) Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single-institution phase II study. Br J Urol 80: 44-49.

47. Danesi DT, Arcangeli G, Cruciani E, Altavista P, Mecozzi A, et al. (2004) Conservative treatment of invasive bladder carcinoma by transurethral resection, protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy: long term results. Cancer 101: 2540-2548.

48. George L, Bladou F, Bardou VJ, Gravis G, Tallet A, et al. (2004) Clinical outcome in patients with locally advanced bladder carcinoma treated with conservative multimodality therapy. Urology 64: 488-493.

49. Cobo M, Delgado R, Gil S, Herruzo I, Baena V, et al. (2006) Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer. Clin Transl Oncol 8: 903-911.

50. Perdona S, Autorino R, Damiano R, De Sio M, Morrica B, et al. (2008) Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: a multi-institutional, long-term experience. Cancer 112: 75-83.

51. Hussain MH, Glass TR, Forman J, Sakr W, Smith DC, et al. (2001) Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study. J Urol 165: 56-60; discussion 60-51.

52. Lagrange JL, Bascoul-Mollevi C, Geoffrois L, Beckendorf V, Ferrero JM, et al. (2011) Quality of life assessment after concurrent chemoradiation for invasive bladder cancer: results of a multicenter prospective study (GETUG 97-015). Int J Radiat Oncol Biol Phys 79: 172-178.

53. Weiss C, Wittlinger M, Engehausen DG, Krause FS, Ott OJ, et al. (2008) Management of superficial recurrences in an irradiated bladder after combined-modality organ-preserving therapy. Int J Radiat Oncol Biol Phys 70: 1502-1506.

54. Zietman AL, Grocela J, Zehr E, Kaufman DS, Young RH, et al. (2001) Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder. Urology 58: 380-385.

55. Shipley WU, Kaufman DS, Zehr E, Heney NM, Lane SC, et al. (2002) Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology 60: 62-67; discussion 67-68.

56. Eswara JR, Efstathiou JA, Heney NM, Paly J, Kaufman DS, et al. (2012) Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. J Urol 187: 463-468.

57. Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, et al. (2013) ICUD-EAU International Consultation on Bladder Cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 63: 45-57.

58. Chakravarti A, Winter K, Wu CL, Kaufman D, Hammond E, et al. (2005) Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 62: 309-317.

59. Hussain MH, MacVicar GR, Petrylak DP, Dunn RL, Vaishampayan U, et al. (2007) Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol 25: 2218-2224.

60. Choudhury A, Nelson LD, Teo MT, Chilka S, Bhattarai S, et al. (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res 18: 7017–7026.

61. Laurberg JR, Brems-Eskildsen AS, Nordentoft I, Fristrup N, Schepeler T, et al. (2012) Expression of TIP60 (tat-interactive protein) and MRE11 (meiotic recombination 11 homolog) predict treatment-specific outcome of localised invasive bladder cancer. BJU Int 110: E1228-1236.