The Role of Chemotherapy and Radiotherapy in the Surgical Management of Muscle Invasive Bladder Cancer

  • Joshua Luck Medical Student, University of Oxford, United Kingdom
Keywords: Chemoradiotherapy, combined modality therapy, urinary bladder neoplasms, cystectomy


The management of muscle invasive bladder cancer represents an unresolved clinical challenge. Invasive urothelial carcinomas are associated with high mortality rates and early metastatic disease. Radical cystectomy is a recognized standard of care, although disease-free survival outcomes remain suboptimal. The limitations of pre-operative clinical staging, as well as the complex natural history of the disease, precludes the introduction of simple management protocols. To what degree chemotherapy and radiotherapy may be useful in the surgical management of invasive bladder cancer remains contentious. This literature review critically examines the benefits, risks and difficulties of each approach, with an emphasis on individually tailored therapy.

Author Biography

Joshua Luck, Medical Student, University of Oxford, United Kingdom

Joshua Luck is a sixth year medical student at the University of Oxford, United Kingdom.


1. Rosario DJ, Becker M, Anderson JB. The changing pattern of mortality and morbidity from radical cystectomy. BJU Int. 2000 Mar;85(4):427-30.
2. Lunt CR, Maddineni SB, Brough R. Bladder Cancer. Br J Med Surg Urol. 2012 Mar;5(2):95-103.
3. Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014 Apr;65(4):778-92.
4. Feldman AR, Kessler L, Myers MH, Naughton MD. The prevalence of cancer. Estimates based on the Connecticut Tumor Registry. N Engl J Med. 1986 Nov 27;315(22):1394-7.
5. Eylert M, Hounsome L, Persad R, Bahl A, Jefferies E, Verne J, et al. Falling bladder cancer incidence from 1990 to 2009 is not producing universal mor¬tality improvements. J Clin Urol. 2013 Jul 4;7(2):90-8.
6. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009 Jul 21;6(7):e1000100.
7. Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organiza¬tion/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Path. 1998 Dec;22(12):1435-48.
8. Edge, Byrd, Compton, Fritz, Greene, Trotti. AJCC Cancer Staging Manual. New York: Springer; 2010.
9. Stein JP, Skinner DG. Results with radical cystectomy for treating bladder cancer: a 'reference standard' for high-grade, invasive bladder cancer. BJU Int. 2003 Jun;92(1):12-7.
10. Hudson MA, Herr HW. Carcinoma in situ of the bladder. J Urol. 1995;153(3):564-72.
11. Shariat SF, Palapattu GS, Karakiewicz PI, Rogers CG, Vazina A, Bastian PJ, et al. Discrepancy between clinical and pathologic stage: impact on prognosis after radical cystectomy. Eur Urol. 2007 Jan;51(1):137-49.
12. Jakse G, Algaba F, Malmstrom PU, Oosterlinck W. A second-look TUR in T1 transi¬tional cell carcinoma: why? Eur Urol. 2004 May;45(5):539-46.
13. Brauers A, Buettner R, Jakse G. Second resection and prognosis of primary high risk superficial bladder cancer: is cystectomy often too early? J Urol. 2001 Mar;165(3):808-10.
14. Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bla¬dder: a contemporary series from the Bladder Cancer Research Consortium. J Urol. 2006 Dec;176(6 Pt 1):2414-22.
15. Paik ML, Scolieri MJ, Brown SL, Spirnak JP, Resnick MI. Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy. J Urol. 2000 Jun;163(6):1693-6-
16. Barentsz JO, Jager GJ, Witjes JA, Ruijs JH. Primary staging of urinary bladder carcinoma: the role of MRI and a comparison with CT. Eur Rad. 1996;6(2):129-33.
17. Barentsz JO, Jager GJ, van Vierzen PB, Witjes JA, Strijk SP, Peters H, et al. Staging urinary bladder cancer after transurethral biopsy: value of fast dynamic contrast-enhanced MR imaging. Radiology. 1996 Oct;201(1):185-93.
18. Bellmunt J, Orsola A, Leow JJ, Wiegel T, De Santis M, Horwich A. Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up. Ann Onc. 2014 Sep;25(Suppl 3):iii40-8.
19. Holzbeierlein JM, Lopez-Corona E, Bochner BH, Herr HW, Donat SM, Russo P, et al. Partial cystectomy: a contemporary review of the Memorial Sloan-Ke¬ttering Cancer Center experience and recommendations for patient selection. J Urol. 2004 Sep;172(3):878-81.
20. Hautmann RE, de Petriconi R, Gottfried HW, Kleinschmidt K, Mattes R, Paiss T. The ileal neobladder: complications and functional results in 363 patients after 11 years of followup. J Urol. 1999 Feb;161(2):422-7.
21. Sanchez-Ortiz RF, Huang WC, Mick R, Van Arsdalen KN, Wein AJ, Malkowicz SB. An interval longer than 12 weeks between the diagnosis of muscle inva¬sion and cystectomy is associated with worse outcome in bladder carcinoma. J Urol. 2003 Jan;169(1):110-5.
22. Cody JD, Nabi G, Dublin N, McClinton S, Neal DE, Pickard R, et al. Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy. Cochrane Database Syst Rev. 2012 Feb 15;2:CD003306.
23. Svatek RS, Shariat SF, Novara G, Skinner EC, Fradet Y, Bastian PJ, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prog¬nosis in an international radical cystectomy cohort. BJU Int. 2011 Mar;107(6):898-904.
24. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Onc. 2001 Feb 1;19(3):666-75.
25. Herr HW, Bajorin DF, Scher HI. Neoadjuvant chemotherapy and bladder-sparing sur¬gery for invasive bladder cancer: ten-year outcome. J Clin Onc. 1998 Apr;16(4):1298-301.
26. Caffo O, Fellin G, Graffer U, Luciani L. Assessment of quality of life after cys¬tectomy or conservative therapy for patients with infiltrating bladder carcinoma. A survey by a self-administered questionnaire. Cancer. 1996 Sep 1;78(5):1089-97.
27. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40.
28. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alo¬ne for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66.
29. Sherif A, Holmberg L, Rintala E, Mestad O, Nilsson J, Nilsson S, et al. Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol. 2004 Mar;45(3):297-303.
30. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant che¬motherapy in invasive bladder cancer: a systematic review and meta-analy¬sis. Lancet. 2003 Jun 7;361(9373):1927-34.
31. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant che¬motherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) me¬ta-analysis collaboration. Eur Urol. 2005 Aug;48(2):202-5.
32. Winquist E, Kirchner TS, Segal R, Chin J, Lukka H; Genitourinary Cancer Disease Site Group, Cancer Care Ontario Program in Evidence-based Care Practice Guide¬lines Initiative. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004 Feb;171(2 Pt 1):561-9.
33. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cis¬platin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Onc. 2000 Sep;18(17):3068-77.
34. Herchenhorn D, Dienstmann R, Peixoto FA, de Campos FS, Santos VO, Morei¬ra DM, et al. Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma. Int Braz J Urol. 2007 Sep-Oct;33(5):630-8.
35. Dash A, Pettus JA 4th, Herr HW, Bochner BH, Dalbagni G, Donat SM, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcino¬ma of the bladder: a retrospective experience. Cancer. 2008 Nov 1;113(9):2471-7.
36. Blick C, Hall P, Pwint T, Al-Terkait F, Crew J, Powles T, et al. Accelerated me¬thotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder. Cancer. 2012 Aug 15;118(16):3920-7.
37. Chester JD, Hall GD, Forster M, Protheroe AS. Systemic chemotherapy for patients with bladder cancer--current controversies and future directions. Cancer Treat Rev. 2004 Jun;30(4):343-58.
38. Sternberg CN, Donat SM, Bellmunt J, Millikan RE, Stadler W, De Mulder P, et al. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urolology. 2007 Jan;69(1 Suppl):62-79.
39. Donat SM, Shabsigh A, Savage C, Cronin AM, Bochner BH, Dalbagni G, et al. Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a hi¬gh-volume tertiary cancer center experience. Eur Urol. 2009 Jan;55(1):177-85.
40. Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Mansson W, Sa¬galowsky A, et al. Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol. 2010 Jun;57(6):983-1001.
41. Skinner DG, Daniels JR, Russell CA, Lieskovsky G, Boyd SD, Nichols P, et al. The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial. J Urol. 1991 Mar;145(3):459-64.
42. Lehmann J, Franzaring L, Thuroff J, Wellek S, Stockle M. Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int. 2006 Jan;97(1):42-7.
43. Stockle M, Meyenburg W, Wellek S, Voges G, Gertenbach U, Thuroff JW, et al. Advanced bladder cancer (stages pT3b, pT4a, pN1 and pN2): improved survival after radical cystectomy and 3 adjuvant cycles of chemotherapy. Results of a controlled prospective study. J Urol. 1992 Aug;148(2 Pt 1):302-6.
44. Advanced Bladder Cancer Meta-analysis Collaboration. Adjuvant chemo¬therapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis Co¬llaboration. Eur Urol. 2005 Aug;48(2):189-99.
45. Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, et al. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol. 2012 Mar;23(3):695-700.
46. Lehmann J, Kuehn M, Fischer C, Volkmer B, Rundsted Fv, Albers P, et al. Randomized phase III study of adjuvant versus progression-triggered treat¬ment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemothe¬rapy (CBC) (AUO-trial AB22/00). J Clin Onc. 2013;31(suppl 6;abstr 250).
47. Studer UE, Bacchi M, Biedermann C, Jaeger P, Kraft R, Mazzucchelli L, et al. Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol. 1994 Jul;152(1):81-4.
48. Sternberg CN, Bellmunt J, Sonpavde G, Siefker-Radtke AO, Stadler WM, Bajorin DF, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol. 2013 Jan;63(1):58-66
49. Meeks JJ, Bellmunt J, Bochner BH, Clarke NW, Daneshmand S, Galsky MD, et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2012 Sep;62(3):523-33.
50. Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D, et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Onc. 2011 Sep 1;29(25):3443-9.
51. Hayter CR, Paszat LF, Groome PA, Schulze K, Math M, Mackillop WJ. A po¬pulation-based study of the use and outcome of radical radiotherapy for in¬vasive bladder cancer. Int J Radiat Oncol Biol Phys. 1999 Dec 1;45(5):1239-45.
52. Cooke PW, Dunn JA, Latief T, Bathers S, James ND, Wallace DM. Long-term risk of salvage cystectomy after radiotherapy for muscle-invasive bladder cancer. Eur Urol. 2000 Sep;38(3):279-86.
53. Yiou R, Patard JJ, Benhard H, Abbou CC, Chopin DK. Outcome of radical cystectomy for bladder cancer according to the disease type at presentation. BJU Int. 2002 Mar;89(4):374-8.
54. Shelley MD, Wilt TJ, Barber J, Mason MD. A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy
compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice? Clin Oncol (R Coll Radiol). 2004 May;16(3):166-71.
55. Huncharek M, Muscat J, Geschwind JF. Planned preoperative radiation therapy in muscle invasive bladder cancer; results of a meta-analysis. Anti¬cancer Res. 1998 May-Jun;18(3B):1931-4.
56. Shipley WU, Kaufman DS, Zehr E, Heney NM, Lane SC, Thakral HK, et al. Selecti¬ve bladder preservation by combined modality protocol treatment: long-term out¬comes of 190 patients with invasive bladder cancer. Urology. 2002 Jul;60(1):62-7.
57. Kim HL, Steinberg GD. Complications of cystectomy in patients with a history of pelvic radiation. Urology. 2001 Oct;58(4):557-60.
58. Mameghan H, Fisher R, Mameghan J, Brook S. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder. Int J Radiat Oncol Biol Phys. 1995 Jan 15;31(2):247-54.
59. Huddart RA, Hall E, Hussain SA, Jenkins P, Rawlings C, Tremlett J, et al. Randomized noninferiority trial of reduced high-dose volume versus standard volume radiation therapy for muscle-invasive bladder cancer: results of the BC2001 trial (CRUK/01/004). Int J Radiat Oncol Biol Phys. 2013 Oct 1;87(2):261-9.
60. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally ad¬vanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53.
61. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCC¬CR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet. 1996 Oct 19;348(9034):1049-54.
62. James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, et al. Ra¬diotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88.
63. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent car¬bogen and nicotinamide in bladder carcinoma. J Clin Oncol. 2010 Nov 20;28(33):4912-8.
64. Sabaa MA, El-Gamal OM, Abo-Elenen M, Khanam A. Combined modality treatment with bladder preservation for muscle invasive bladder cancer. Urol Oncol. 2010 Jan-Feb;28(1):14-20.
65. Zapatero A, Martin de Vidales C, Arellano R, Bocardo G, Perez M, Rios P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74.
66. Milosevic M, Gospodarowicz M, Zietman A, Abbas F, Haustermans K, Moonen L, et al. Radiotherapy for bladder cancer. Urology. 2007 Jan;69(1 Suppl):80-92.
67. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Gui¬delines in Oncology (NCCN Guidelines®) Bladder Cancer. Washington, PA; 2006.
68. Clark PE, Agarwal N, Biagioli MC, Eisenberger MA, Greenberg RE, Herr HW, et al. Bladder cancer. J Natl Compr Canc Netw. 2013 Apr 1;11(4):446-75.
69. Tiguert R, Lessard A, So A, Fradet Y. Prognostic markers in muscle invasive bladder cancer. World J Urol. 2002 Aug;20(3):190-5.
70. Raghavan D. Molecular targeting and pharmacogenomics in the mana¬gement of advanced bladder cancer. Cancer. 2003 Apr 15;97(8 Suppl):2083-9.
71. Kamat AM, Hegarty PK, Gee JR, Clark PE, Svatek RS, Hegarty N, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Screening, diagnosis, and molecular markers. Eur Urol. 2013 Jan;63(1):4-15.
How to Cite
Luck, J. (2014). The Role of Chemotherapy and Radiotherapy in the Surgical Management of Muscle Invasive Bladder Cancer. International Journal of Medical Students, 2(3), 125-131.