Clinical Scenario: Persistent CIS and High-Grade Ta Bladder Cancer After BCG

Clinical history: 79-Year-old man who has a persistent CIS despite induction and maintenance BCG for 6 months
  • Maurizio BrausiEmail author


The standard treatment for Ta-T1 high-grade (G3) TCC of the bladder and CIS is TUR followed by BCG full dose once a week for 6 weeks and then at month 3, 6, 12, 18, 24, 30, 36 according to the SWOG schedule.

The efficacy of adjuvant immunotherapy in the elderly has been discussed and questioned. A reduced activity of BCG has been reported due to the impairment of the immune-system response than in patients more than 75 years of age.

When a patient with CIS presents with a recurrence during BCG therapy it can be called BCG failure. The therapy of patients with CIS who experienced a BCG failure is radical cystectomy, according to international guidelines. However, in elderly patients with co-morbidities unfit or refusing surgery a conservative treatment can be adopted.

Chemotherapy with MMC and hyperthermia (Synergo) once a week for 6 weeks should be the first choice. A second option for these patients with recurrent CIS is the administration of Gemcitabine high dose (2,000 mg a week) for 6 weeks.

Finally, INF-alfa with BCG has shown efficacy in these patients.


Recurrent carcinoma in situ Elderly BCG failure Alternative treatments 


  1. 1.
    Morales A, Edinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumours. J Urol. 1976;116(2):180–3.PubMedGoogle Scholar
  2. 2.
    Brosman SA. Experience with Bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J Urol. 1982;128(1):27–30.PubMedGoogle Scholar
  3. 3.
    Lamm DL, Blumenstein BA, Cristmann JD, et al. Maintenance Bacillus Calmette-Guerin immunotherapy for recurrent Ta-T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000;163:1124–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical Bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a combined analysis of the published results of randomized clinical trials. J Urol. 2002;168:1964–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Bohle A, Jocham D, Bock PR. Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer a formal meta-analysis of comparative studies on recurrence and toxicity. J Urol. 2003;169: 90–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Sylvester RJ, van der Meijden AP, Witjes JA, et al. Bacillus Calmette-Guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials. J Urol. 2005;174:86–91.PubMedCrossRefGoogle Scholar
  7. 7.
    Han RF, Pan JG. Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with superficial bladder cancer? a meta- analysis of randomized trials. Urology. 2006;67:1216–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Malmstrom PU, Sylvester RJ, Crawford DE, et al. An individual patient data meta-analysis of the long term outcome of randomized studies comparing intravesical Mitomycin C versus bacillus Calmette-Guerin for non muscle invasive bladder cancer. Eur Urol. 2009;56:247–56.PubMedCrossRefGoogle Scholar
  9. 9.
    Sylvester RJ, Brausi MA, Kirkels WJ, et al. Long-term efficacy results of EORTC Genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus Isoniazid in patients with intermediate and high-risk stage TaT1 urothelial carcinoma of the bladder. Eur Urol. 2010;57(Suppl):766–70. 715–34.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Lamm DL, Persad R, Colombel M, et al. Maintenance bacillus Calmette-Guérin: the standard of care for the prophylaxis and management of intermediate- and high-risk non-muscle-invasive bladder cancer. Eur Urol. 2010;9(Suppl):715–34.CrossRefGoogle Scholar
  11. 11.
    Brausi M, Witjes A, Lamm D, et al. A review of current guidelines and best practice recommendations for the management of non-muscle invasive bladder cancer by the international bladder cancer group. J Urol. 2011;186:2158–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillis Calmette-Guérin in intermediate-and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013;63:462–72.PubMedCrossRefGoogle Scholar
  13. 13.
    Shariat S, Milowsky M, Droller M. Bladder cancer in the elderly. Urol Oncol. 2009;27:653–67.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Shariat S, Sfakianos J, Droller M, et al. The effect of age and gender on bladder cancer: a critical review of the literature. BJUI. 2009;105:300–8.CrossRefGoogle Scholar
  15. 15.
    Herr H. Age and outcome of superficial bladder cancer treated with bacille Calmette-Guérin therapy. Urology. 2007;70(1):65–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Joudi F, Smith B, O’Donnell A, et al. The impact of age on the response of patients with superficial bladder cancer to intravesical immunotherapy. J Urol. 2006;175:1634–40.PubMedCrossRefGoogle Scholar
  17. 17.
    Heiner J, Terris M. Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy. Urol Oncol. 2008;26:137–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Babjuk M, Oosterlinck W, Sylvester R et al. European Association of Urology guidelines on TaT1 non muscle invasive bladder cancer. Update march 2009. Arnhem, The Netherlands: European Association of Urology; 2009. Available from
  19. 19.
    Lamm D, Colombel M, Persad R, et al. Clinical recommendations for the management of non-muscle invasive bladder cancer. Eur Urol. 2008;7(Suppl):651–66.CrossRefGoogle Scholar
  20. 20.
    Nieder AM, Brausi M, Lamm D, et al. Management of stage T1 tumors of the bladder: International Consensus Panel. Urology. 2005;66(Suppl 6A):108–25.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Donnell M. Optimizing BCG, therapy. Urol Onc. 2009;27:325–8.CrossRefGoogle Scholar
  22. 22.
    Yates D, Brausi M, Catto J, et al. Treatment options available for bacillus Calmette-Guérin failure in non-muscle-invasive bladder cancer. Eur Urol. 2012;62: 1088–96.PubMedCrossRefGoogle Scholar
  23. 23.
    Lammers RJM, Witjes JA, Innam BA, et al. The role of combined regimen with intravesical chemotherapy and hyperthermia in the management of non-muscle invasive bladder cancer: a systematic review. Eur Urol. 2011;60:81–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Urology Ausl ModenaB. Ramazzini HospitalCarpi-ModenaItaly

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