Skip to main content
SpringerLink
Log in

Immunotherapy of Superficial Bladder Cancer

  • Practical Therapeutics
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Superficial transitional cell carcinoma of the bladder is a common tumour that can readily be removed surgically. However, it recurs in as many as 88% of patients, making it an ideal malignancy for immunoprophylaxis or chemoprevention.

Immunotherapy with bacille Calmette-Guérin (BCG) is increasingly recognised as the most effective treatment for superficial bladder cancer, particularly for high grade tumours and carcinoma in situ. Intravesical BCG instillation stimulates cellular immunity, cytokine production and antigen presentation. Unlike intravesical chemotherapy, treatment with BCG induces protection from tumour recurrence that persists for more than 5 years. Current optimal induction regimens use instillation of BCG once weekly for 6 weeks, followed by a 6-week rest period and 3 additional weekly instillations. This regimen results in a complete response in carcinoma in situ in 82% of patients. In combination with maintenance BCG immunotherapy using instillation once weekly for 3 weeks at 6-month intervals for 3 years, long term disease-free status is achieved in 83% of patients. This regimen is found to improve protection from recurrence by 33% when compared with a single 6-week induction treatment, and further reduces disease progression and cancer mortality.

Controlled studies have demonstrated that BCG is superior to standard chemotherapies, including thiotepa, doxorubicin and mitomycin, and to alternative immunotherapies including interferon-α and keyhole limpet haemocyanin. However, these alternative therapies provide treatment options for patients who have toxic reactions or fail to respond to BCG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lamm DL, Griffith JG. The place of intravesical chemotherapy as defined by results of prospective randomized studies (substances and treatment schemes). In: Schröder FH, editor. EORTC Genitourinary Group Monograph 11: Recent progress in bladder and kidney cancer. New York: Wiley-Liss, 1992: 43–53

    Google Scholar 

  2. Messing EM, Young TB, Hunt VB, et al. Comparison of bladder cancer outcome in screened and unscreened men. J Natl Cancer Inst. Submitted

  3. Heney NM, Ahmed S, Flanagan MJ, et al. Superficial bladder cancer: progression and recurrence. J Urol 1983; 130: 1083

    PubMed  CAS  Google Scholar 

  4. Lamm DL. Carcinoma in situ. Urol Clin North Am 1992; 19: 499–508

    PubMed  CAS  Google Scholar 

  5. Lamm DL, Riggs DR, Traynelis CL, et al. Failure of current intravesical chemotherapy prophylaxis in superficial transitional cell carcinoma of the bladder. J Urol. In press

  6. Morales A, Eidinger D, Bruce AW. Intracavitary bacillus Calmette-Guérin in the treatment of superficial bladder tumors. J Urol 1976; 116: 180

    PubMed  CAS  Google Scholar 

  7. Davies M. Bacillus Calmette-Guérin as an antitumor agent: the interaction with cells of the mammalian immune system. Biochim Biophys Acta 1982; 651: 143

    PubMed  CAS  Google Scholar 

  8. Sosnowski JT, Lamm DL. Immunotherapy for bladder cancer. Urol Annu 1990; 4: 123–56

    Google Scholar 

  9. Haaff EO, Catalona WJ, Ratliff TL. Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG. J Urol 1986; 136: 970

    PubMed  CAS  Google Scholar 

  10. Morales A, Ottenhof PC. Clinical application of a whole blood assay for human natural killer (NK) cell activity. Cancer 1983; 52: 667

    Article  PubMed  CAS  Google Scholar 

  11. Ratliff TL, Gillen D, Catalona WJ. Requirement of a thymus dependent immune response for BCG-mediated antitumor activity. J Urol 1987; 137: 155

    PubMed  CAS  Google Scholar 

  12. Bohle A, Thanhauser A, Ulmer AJ, et al. Dissecting the immunobiological effects of Bacillus Calmette-Guérin (BCG) in vitro: evidence of a distinct BCG-activated killer (BAK) cell phenomenon. J Urol 1993; 150: 1032

    Google Scholar 

  13. Ratliff TL, Hudson MA, Catalona WJ. Strategy for improving therapy of superficial bladder cancer. World J Urol 1991; 9: 95

    Article  Google Scholar 

  14. Becich MJ, Carroll S, Ratliff TL. Internalization of Bacille Calmette-Guérin by bladder tumor cells. J Urol 1991; 145: 1316

    PubMed  CAS  Google Scholar 

  15. Morales A, Nickel JC. Immunotherapy of superficial bladder cancer with BCG. World J Urol 1986; 3: 209

    Article  Google Scholar 

  16. Garden RJ, Liu BCS, Redwood SM, et al. Bacillus Calmette-Guérin abrogates in vitro invasion and motility of human bladder tumor cells via fibronectin interaction. J Urol 1992; 148: 900

    PubMed  CAS  Google Scholar 

  17. Herr HW, Laudone VP, Whitmore WF. An overview of intravesical therapy for superficial bladder tumors. J Urol 1987; 138: 1363

    PubMed  CAS  Google Scholar 

  18. Herr HW, Laudone VP, Badalament RA, et al. Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer. J Clin Oncol 1988; 6: 1450

    PubMed  CAS  Google Scholar 

  19. Herr HW. Transurethral resection and intravesical therapy of superficial bladder tumors. Urol Clin North Am 1991; 18: 525–8

    PubMed  CAS  Google Scholar 

  20. Lamm DL, Blumenstein BA, Crawford ED, et al. A randomized trial of intravesical doxorubicin and immunotherapy with Bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med 1991; 325: 1205

    Article  PubMed  CAS  Google Scholar 

  21. Pagano F, Bassi P, Milani C, et al. A low dose bacillus Calmette-Guérin regimen in superficial bladder cancer therapy: is it effective? J Urol 1991; 146: 32

    PubMed  CAS  Google Scholar 

  22. Traynelis CL, Lamm DL. Current status of intravesical therapy for bladder cancer. Urol Annu 1994; 8: 113–43

    Google Scholar 

  23. Morales A. Treatment of carcinoma in situ of the bladder with BCG: a phase II trial. Cancer Immunol Immunother 1980; 9: 69

    Article  Google Scholar 

  24. Herr HW. Carcinoma in situ of the bladder. Semin Urol 1983: 1: 15

    PubMed  CAS  Google Scholar 

  25. Lamm DL. Bacillus Calmette-Guérin immunotherapy for bladder cancer. J Urol 1985; 134: 40

    PubMed  CAS  Google Scholar 

  26. Brosman S. The use of bacillus Calmette-Guérin in the therapy of bladder carcinoma in situ. J Urol 1985; 134: 36

    PubMed  CAS  Google Scholar 

  27. Kelley DR, Ratliff DL, Catalona WJ, et al. Intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer: effect of bacillus Calmette-Guérin viability on treatment results. J Urol 1985; 134: 48

    PubMed  CAS  Google Scholar 

  28. Schellhammer PF, Ladaga LE, Fillion MB. Bacillus Calmette-Guérin for superficial transitional cell carcinoma of the bladder. J Urol 1986; 135: 261

    PubMed  CAS  Google Scholar 

  29. deKernion JB, Huang M-Y, Lindner A, et al. The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Guérin. J Urol 1985; 133: 598

    PubMed  CAS  Google Scholar 

  30. Solaway MS, Perry A. Bacillus Calmette-Guérin for treatment of superficial transitional cell carcinoma of the bladder in patients who have failed thiotepa and/or mitomycin C. J Urol 1987; 137: 871

    Google Scholar 

  31. Kavoussi LR, Torrence RJ, Gillen DP, et al. Results of 6 weekly intravesical bacillus Calmette-Guérin instillations on the treatment of superficial bladder tumours. J Urol 1988; 139: 935

    PubMed  CAS  Google Scholar 

  32. Rintala E, Jauhiainen K, Alfthan O, et al. Mitomycin-C and BCG in intravesical chemotherapy and immunotherapy of superficial bladder cancer. In: Debruyne FMJ, Denis L, van der Meijden A, editors. EORTC Genitourinary Group Monograph 6: BCG in superficial bladder cancer. New York: Alan R Liss, 1989: 271–4

    Google Scholar 

  33. Brosman S. The influence of Tice strain BCG treatment in patients with transitional cell carcinoma in situ. In: Debruyne FMJ, Denis L, van der Meijden A, editors. EORTC Genitourinary Group Monograph 6: BCG in superficial bladder cancer. New York: Alan R Liss, 1989: 193–205

    Google Scholar 

  34. Steg A, Leleu C, Boccon-Gibod L, et al. Traitement des tumeurs superficielles de vessie par BCG-therapie intra-vesicale. In: Di Silverio F, Steg A, editors. International workshop in urology: new trends in bladder cancer chemotherapy. Rome: Acta Medica, 1988: 203–12

    Google Scholar 

  35. Prescott S, James K, Hargreave TB, et al. Immunopathological effects of intravesical BCG therapy. In: Debruyne FMJ, Denis L, van der Meijden A, editors. EORTC Genitourinary Group Monograph 6: BCG in superficial bladder cancer. New York: Alan R Liss, 1989: 93–105

    Google Scholar 

  36. Reitsma DJ, Guinan P, Lamm DL, et al. Long-term effect of intravesical bacillus Calmette-Guérin (BCG) Tice strain on flat carcinoma in situ of the bladder. In: Debruyne FMJ, Denis L, van der Meijden A, editors. EORTC Genitourinary Group Monograph 6: BCG in superficial bladder cancer. New York: Alan R Liss, 1989: 171–85

    Google Scholar 

  37. Lamm DL, Crawford ED, Blumenstein B, et al. Maintenance BCG immunotherapy of superficial bladder cancer: a randomized prospective Southwest Oncology Group study [abstract]. J Urol 1992; 147(4): 274A

    Google Scholar 

  38. Bast Jr RC, Zbar B, Borsos T, et al. BCG and cancer 1. N Engl J Med 1974; 290: 1413

    Article  PubMed  Google Scholar 

  39. Lamm DL, Reichert DF, Harris SC, et al. Immunotherapy of murine transitional cell carcinoma. J Urol 1982; 128: 1107

    Google Scholar 

  40. Morales A, Nickel JC, Wilson JWL. Dose response of Bacillus Calmette-Guérin in the treatment of superficial bladder cancer. J Urol 1992; 147: 1256

    PubMed  CAS  Google Scholar 

  41. Bassi P, Milani C, Piazza N, et al. In search of the optimum BCG regimen. In: Pagano F, Bassi P, editors. Monographs in urology: BCG immunotherapy in superficial bladder cancer. 1994: 53–61

    Google Scholar 

  42. Ratliff TL, Kavoussi LR, Catalona WJ. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer. J Urol 1988; 139: 410–4

    PubMed  CAS  Google Scholar 

  43. P’ng KBF, Walsh MD, Seymour GJ, et al. The adverse effect of clot inhibiting drugs on intravesical Bacillus Calmette-Guérin efficacy for superficial bladder cancer. Aust NZ J Surg 1993: 63(2): 127–30

    Article  Google Scholar 

  44. Rogerson JW. Intravesical bacille Calmette-Guérin in the treatment of superficial transitional cell carcinoma of the bladder. Br J Urol 1994; 73: 655–8

    Article  PubMed  CAS  Google Scholar 

  45. Lamm DL. Bacillus Calmette-Guérin immunotherapy lor bladder cancer. J Urol 1985; 134: 40–7

    PubMed  CAS  Google Scholar 

  46. Badalament RA, Herr HW, Wong GY, et al. A prospective randomized trial of maintenance versus nonmaintenance intravesical Bacillus Calmette-Guérin therapy of superficial bladder cancer. J Clin Oncol 1987; 5: 441

    PubMed  CAS  Google Scholar 

  47. Hudson MA, Ratliff TL, Gillen DP, et al. Single course versus maintenance Bacillus Calmette-Guérin therapy for superficial bladder tumors: a prospective, randomized trial. J Urol 1987; 138: 295

    PubMed  CAS  Google Scholar 

  48. Lamm DL. Complications of Bacillus Calmette-Guérin immunotherapy. Urol Clin North Am 1992; 19: 565–72

    PubMed  CAS  Google Scholar 

  49. Sargent ER, Williams RD. Immunotherapeutic alternatives in superficial bladder cancer. Urol Clin North Am 1992; 19: 581–9

    PubMed  CAS  Google Scholar 

  50. Grups J, Frohmuller H, Ackermann R. Can recombinant human gamma-2 interferon prevent recurrence of high-grade superficial bladder tumors? Cancer Detect Prev 1987; 10: 405

    PubMed  CAS  Google Scholar 

  51. Torti F, Shortliffe L, Williams R, et al. Alpha-interfcron in superficial bladder cancer: a Northern California Oncology Group study. J Clin Oncol 1988; 6: 476

    PubMed  CAS  Google Scholar 

  52. Glashan R. A randomized controlled study of intravesical alpha-2b-interferon in carcinoma in situ of the bladder. J Urol 1990; 144: 658

    PubMed  CAS  Google Scholar 

  53. Calais da Silva F. Interferon alpha 2b 60 millions vs 100 millions in intravesical prophylaxis of superficial bladder cancer. J Urol 1993; 149 Suppl.: 282A

    Google Scholar 

  54. Kalble T, Beer M, Staehler G. Intravesical prophylaxis with BCG versus interferon A for superficial bladder cancer [abstract]. J Urol 1994; 151(22): 233a

    Google Scholar 

  55. Olsson CA, Chute R, Rao CN. Immunologic reduction of bladder cancer recurrence rate. J Urol 1974; 111: 173

    PubMed  CAS  Google Scholar 

  56. Jurincic C, Engelmann U, Gasch J. Immunotherapy in bladder cancer with keyhole-limpet hemocyanin: a randomized study. J Urol 1988; 139: 723

    PubMed  CAS  Google Scholar 

  57. Flamm J, Bucher A, Holtl W. Recurrent superficial transitional cell carcinoma of the bladder: adjuvant topical chemotherapy versus immunotherapy — prospective randomized trial. J Urol 1990; 144: 260

    PubMed  CAS  Google Scholar 

  58. Rios A, Stringfellow DA, Fitzpatrick FA, et al. Phase I study of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP), an oral interferon inducer in cancer patients. J Biol Resp Modif 1986; 5: 330

    CAS  Google Scholar 

  59. Simmons WB, Reichert DF, Lucio RM, et al. Pyrimidinone interferon inducers in the treatment of murine transitional cell carcinoma [abstract]. J Urol 1983; 129: 169

    Google Scholar 

  60. Sarosdy MF, Lowe BA, Schellhammer PF, et al. Bropirimine immunotherapy of bladder CIS: positive phase II results of an oral interferon inducer. J Urol 1994; 151 Suppl.: 304

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, West Virginia University School of Medicine, Morgantown, West Virginia, USA

    Donald L. Lamm & Dale R. Riggs

Authors
  1. Donald L. Lamm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dale R. Riggs
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamm, D.L., Riggs, D.R. Immunotherapy of Superficial Bladder Cancer. Clin. Immunother. 2, 331–341 (1994). https://doi.org/10.1007/BF03259493

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259493

Keywords

Search

Navigation