PTU - Polskie Towarzystwo Urologiczne
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BCG immunotherapy in superficial bladder cancer
Article published in Urologia Polska 2001/54/3.


Anna Kołodziej, Janusz Dembowski
Katedra i Klinika Urologii Akademii Medycznej we Wrocławiu Kierownik kliniki: prof, dr hab. Jerzy Lorenz


urinary bladder, bladder carcinoma, BCG therapy


Bacillus Calmcttc-Guerin (BCG) has been used for over 20 years now as adjuvant treatment for superficial bladder cancer. Al present, BCG immunotherapy for superficial bladder cancer is considered one of the most efficacious treatments and probably represents the most successful form of immunotherapy of solid tumours in humans. At the start of this new therapy in 1976 by Morales, a number of controversies existed. It was unknown which dose was optimal, which treatment scheme should be used and whether there was an optimal BCG strain. The working mechanism of BCG was not understood and there were problems about the toxicity of BCG intravesical therapy and how to deal with it. This article describes the problems, which are unsolved in BCG therapy and presented this, on which were reached consensus.
In searching for the appropriate BCG strain, the analysis of the results of 7 substrains has made clear that no particular strain has shown superiority over others. The standard treatment in every case is an initial six-week induction course with one installation every week. For tumors without a high recurrence or progression potential, this is usually sufficient. It is also clear that maintenance therapy is the therapy of choice for patients with carcinoma in situ and with high-risk tumors. However, the high rate of side effects associated with maintenance therapy and the prolonged duration of the BCG-induccd cystitis, which can result in discontinuation of the therapy for some patients, present a problem. Especially, that it is difficult to distinguish between therapy-related symptoms that may indicate efficacy of BCG and symptoms that may represent adverse effects. Because the overall side effects of BCG-instillations are more pronounced than of chemotherapeutic drugs, attempts have been made to reduce toxicity of BCG-therapy without affecting the efficacy of it. Several studies were made try to reduced toxicity by reducing the dose of BCG, but the topic of low-dose protocols is still controversial.
Intravesical therapy with BCG has proven to be very effective in the prophylaxis and treatment of superficial bladder tumors and carcinoma in situ. Controlled clinical studies from many countries have demonstrated the effectiveness of BCG therapy and in most series, BCG is superior to intravesical chemotherapy. Because of the more pronounced side effects, the risk and benefit for the individual patient should be considered in each case.


  1. 1. Morales A, Eidinger D, Bruce A: Intracavitary Bacillus Calmetie--Glterin in the treatment oj superficial bladder tumors. J Urol 1976; lid; 180-183.
  2. 2. Zbar 13, Bernstein ID. and Rapp H: ImmuOlhcrapy of guinea pin cancer with BCG Cancer. B1974; 1532-1540.
  3. 3. Kelley D, Ratliff T, Catalona W et al: Intravesical bacillus Calmetie-•Guerin therapy for superficial bladder cancer. Effect of bacillus Cal-mette-Guerin viability on treatment results. J Urol, 1985; 134; 48-53.
  4. 4. Witjcs J, van dcr Meijden ATM, Witjes W, Doesburg W: Debrouy-ne I\\\'M] and members of the Dutch South-Last Cooperative Urologi-cal Group: A randomized, prospective study comparing instilalions of Mitomyein-C. BCG - Vice and BCG-RIVM inpTa-pTl tumours and primary carcinoma in silu of the urinary bladder. Eur J Cancer 1993: 29A; 1672-1676.
  5. 5. Power C, Wei G, Bretshner P: Mycobacterial dose defines the Tli!/Th2nalure of the immune response independly of whether immunisation is administered by the intravenous, subcutaneous or intradermal route. Infect Immun 1998; 66 (No 12); 5743-5750.
  6. 6. Pagano F, Bassi P, Milani C cl al: A low dose bacillus Calmette-Gu-erin regimen in superficial bladder cancer therapy: Is it effective? J Urol 1991; 146; 25-32.
  7. 7. Morales A, Nickel C. Wilson J: Dose-response of bacillus Calmetie-■Guerin in the treatment of superficial bladder cancer. J Urol 1992; 147; 1256-1258.
  8. 8. Lamm D, Brent A, Blumcnslein J et al: Maintenance bacillus Cal-mette-Guerin immunotherapy for recurrent Ta. 77 and carcinoma in situ transitional cell carcinoma of the bladder: A randomised. Southwest Oncology Group Study. J Urol 2000; 163; 1124-1129.
  9. 9. Martinez Pineiro JA, Jimenez LOJ, et al: Intravesical therapy comparing BCG, Adriamycin and Thiotepa in 200 patients with superficial bladder cancer: a randomised prospective study. In: Debruyne I\\\'M./. Denis I. and Meijden Al\\\'M van der (eds), EORTC Genito-Uri-nary Group Monograph 6: BCG in superficial Bladder Cancer. New York 1989; Liss: 237-252.
  10. 10. Lamm DL. Blumcnslein B. Sarosdy M et al: Significant long-term patient benefit with BCG maintenance therapy. J Urol 1997; 157; 831-833.
  11. 11. Lamm DL, Crawford ED. BlumensteinB A ct a: Randomised inter-group comparison of bacillus Calmette-Giterin immunotherapy andMitomycin C chemotherapy prophylaxis in superficial transitional cell carcinoma of the bladder. Urol Oncol 1995; 1; 119-126.
  12. 12. Reijke TJ Boer L, Kurlh H Schamhart D: Urinary cytokines during intravesical Bacillus Calmette-Giterin therapy for superficial bladder cancer: processing stability and prognostic value. J Urol 1996; 155; 477-482.
  13. 13. Bassi P. Spinadin R. Carando R et al: Modified induction course: A solution to side effects? Eur Urol 2000: 37 (suppl); 31-32.
  14. 14.. Vegt R van der Meijden A. Sylvester R and other members of the EORTC GU Group: Does Isoniazid reduce side effects of intravesical bacillus Calmette-Guerin therapy in superficial bladder cancer? Interim results of EORTC protocol 30911.
  15. 15. Lamm DL: Carcinoma in situ. Urol Clin N Am 1991; 19; 565-572.
  16. 16. Hcrr II, Pinsky C, Whitmore W et al: Long term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of bladder. .1 Urol 1986; 135: 265-269.
  17. 17. Brosman SA: Bacillus Calmette-Guerin immunotherapy. Techniques and results. Urol Clin N Am 1992; 19; 557-564.
  18. 18. Lamm D: Bacillus Calmette-Guerin immunotherapy for bladder cancer. J Urol 1985; 134; 40-46.
  19. 19. Herr H, Pinsky C, Whitmore W, et al: Experience with intravesical Bacillus Calmette-Guerin therapy of superficial bladder tumors. Urology 1985; 25; 119.
  20. 20. Melekos M. Chionis II. Pantazakos A et al: Intravesical Bacillus Calmette-Guerin immunoprophylaxis of superficial bladder cancer: results of u controlled prospective trial with modified treatment schedule. J Urol 1993; 149; 744-748.
  21. 21. Herr H, Cookson M. Sogani P et al: Treated natural history ofhigh--risk superficial bladder cancer: 15-year follow-up. J Urol 1996; 155; 494.
  22. 22. Lamm DL: Maintenance versus no-maintenance BCG-immunotherapy of superficial bladder cancer. J Urol 1992; 147; 4. 274 a.
  23. 23. Debruyne FM. vander Meijden. Franscn M et al: Bacillus Calmetie -Guerin versus Mitomycin C intravesical therapy in superficial bladder cancer. Urol 1992; 40 suppl; 11-15.


Anna Kołodziej
Katedra i Klinika Urologii AM
pi. 1 Maja 8
50-0-13 Wroclaw