EXPERIMENTAL AND CLINICAL STUDY OF INTRAVESICAL BCG THERAPY The Role in the Prevention of Recurrence of Superficial Bladder Tumor Atsuyuki Hirano Depa

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1 EXPERIMENTAL AND CLINICAL STUDY OF INTRAVESICAL BCG THERAPY The Role in the Prevention of Recurrence of Superficial Bladder Tumor Atsuyuki Hirano Department of Urology, Wakayama Medical College (Director; Prof. T. Ohkawa) The effects of Tokyo strain bacillus Calmette-Guerin (BCG), which is available in Japan for treatment, were studied in an experimental murine bladder tumor (MBT-2) model prior to clinical study for treatment of superficial bladder tumor. The results were as follows: Tokyo-strain BCG is more effective on the local injection around the tumor than on systemic administration. BCG therapy is more effective at earlier time of small tumor burden. BCG also has a prophylactic effect against the tumor growth. Clinical trial of intravesical instillation of BCG was performed on patients with superficial bladder tumor for prophylaxis of tumor recurrence after transurethral resection of the tumor. In patients of 145 primary cases, the tumor recurrence rate after BCG therapy was estimated, comparing with that of historical control in our department. The historical control groups are consisted of 50 patients who were treated by some intravesical chemotherapy after TUR and 38 patients, who were treated by TUR alone. The tumor recurrence rate in BCG group was significantly lower than that in both control groups. No relationship between PPD responsiveness and the tumor recurrence rate could be detected. On the other hand, in the patients of 36 recurrent cases, evaluation was performed by the tumor recurrence rate comparing with those during the two years prior to BCG therapy. The results demonstrated a statistically significant decrease in recurrent tumor following BCG therapy. Although most of the adverse effects in this study such as bladder irritability, flu-like syndrome and macroscopic hematuria were minimal and tolerable. There were no significant side effects or serious complications attributable to BCG therapy in this series. These results indicate that intravesical Tokyo strain BCG instillation provide prophylactic effects against recurrence of superficial bladder cancer. Key words: superficial bladder cancer, BCG, MBT-2

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9 1) Lerman, RI., Hutter, R. V. P. and Whitmore, W. F. Jr.: Papilloma of the urinary bladder. Cancer, 25, , ) Lutzeyer, W., Ri bben, H. and Dahm, H.: Prognostic parameters in superficial bladder cancer: An analysis of 315 cases. J. Urol., 127, , 1982, 3) Soloway, M. S.: Rationale for intensive intravesical chemotherapy for superficial bladder cancer. J. Urol., 123, , 1980, 4) Herr, H. W., Laudone, V. P. and Whitmore, W. F. Jr.: An overview of intravesical therapy for superficial bladder tumors. J. Urol., 138, , ) Morales, A., Eidinger, D, and Bruce, A. W.: Intracavitary bacillus Calmette-Cuerin in the treatment of superficial bladder tumors. J. Urol., 116, , 1976, 6) Old, L. J., Clarke, D. A., Benacerraf, B. and Goldsmith, M.: The reticuloendothelial system and the neoplastic process. Ann. N. Y. Acad. Sci., 88, , ) Shinka, T., Hirano, A., Uekado, Y. Kyoku, I., Aoshi, H. and Ohkawa, T.: Intravesical bacillus Calmette-Cuerin treatment for superficial bladder tumors. Brit. J. Urol., 63, , 1989, 9) Lamm, D. L., Reichert, D. F., Harris, S. C. and Lucio, R. M.: Immunotherapy of murine transitional cell carcinoma. J. Urol., 128, , 1982, 10) Kelley, D. R., Ratliff, T. L., Catalona, W. J., Shapiro, A., Lage, J. M., Bauer, W. C., Haaff, E. 0. and Dresner, SM.: Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: Effect of bacillus Calmette-Guerin viability on treatment results. J. Urol., 134, 48-53, ) Pang, A. S. D. and Morales, A.: Immunoprophylaxis of a murine bladder cancer with high dose immunizations. J. Urol., 127, , 1982, 12) Zbar, B, and Rapp, H. J.: Immunotherapy of guinea pig cancer with BCG. Cancer, 34, , 1974, 13) Morales, A.: Long-term results and complications of intracavitary bacillus Calmette-Guerin therapy for bladder cancer. J. Urol., 132, , ) dekernion, J. B., Huang, M. -Y., Lindner, A., Smith, R. B. and Kaufman, J. J.: The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Guerin. J. Uroi., 133, , 1985, 15) Haaff, E. O., Dresner, S. M., Ratliff, T. L. and Catalona, W. J.: Two courses of intravesical bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. J. Urol., 136, , ) Brosman, S.: The influence of Tice strain BCG treatment in patients with transitional cell carcinoma in situ. EORTC Genito-Urinary Group Monograph 6: BCG in Superficial Bladder Cancer. p , Alan R. Liss Inc., New York, ) Schellhammer, P. F., Ladaga, L. E. and Fillion, M. B.: Bacillus Calmette-Guerin for superficial transitional cell carcinoma of the bladder. J. Urol., 135, , ) Lamm, D. L.: Bacillus Calmette-Guerin immunotherapy for bladder cancer. J. Uro1., 134, 40-47, 1985, 19) Herr, H. W., Pinsky, C. M., Whitmore, W. F. Jr., Sogani, P. C., Oettgen, H. F. and Melamed, M. R.: Long-term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of the bladder. J. Urol., 135, , ) Morales, A., Ottenhof, P, and Emerson, L.: Treatment of residual, non-infiltrating bladder cancer with bacillus Calmette-Guerin. J. Urol., 125, , 1981, 24) Brosman, S. A.: Experience with bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J. Urol., 128, 27-30, 1982, 25) Catalona, W. J., Hudson, M. A., Gillen, D. P.,

10 Andriole, G. L. and Ratliff, T. L.: Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J. Urol., 137, , ) Lamm, D. L., Steg, A., Boccon-Gibod, L., Morales, A., Hanna, M. G. Jr., Pagano, F., Alfthan, 0., Brosman, S., Fisher, H. A. F., Jakse, G., Chisholm, G. D., vd Meijden, Ad. P. M. and Debruyne, F. M. J.: Complications of bacillus Calmette-Guerin immunotherapy: Review of 2602 patients and comparison chemotherapy complications. EORTC Genito-Urinary Group Monograph 6: BCG in Superficial Bladder Cancer, p , Alan R. Liss, Inc., New York, ) Rawls, W. H., Lamm, DL., Lowe, B. A., Crawford, E. D., Sarosdy, M. F., Montie, J. E., Grossman, H. B, and Scardino, P. T.: Fetal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer. J. Urol., 144, , ) El-demiry, M. I. M., Smith, G., Ritchie, A. W. S., James, K., Cumming, J. A., Hargreave, T. B, and Chisholm, G. D.: Local immune responses after intravesical BCG treatment for carcinoma in situ. Br. J. Urol., 60, , ) Ratliff, T. L., Kavoussi, L. R, and Catalona, W. J.: Role of fibronectin in intravesical BCG therapy for superficial bladder cancer. J. Urol., 139, , 1988, 30) Bohle, A., Nowc, Ch., Ulmer, A. J., Musehold, J., Gerdes, J., Hofstetter, A. G. and Flad, H. -D.: Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette-Guerin immunotherapy. J. Urol., 144, 59-64, ) Netto, N. R. Jr. and Lemos, G. C.: Bacillus Calmette-Guerin immunotherapy of infiltrating bladder cancer. J. Urol., 132, , ) Kelley, D. R., Haaff, E. O., Becich, M., Lage, J., Bauer, W. C., Dresner, S. M., Catalona, W. J. and Prognostic value of purified pro- skin test and granuloma forma- Ratliff, T. L.: tein derivative tion in patients treated with intravesical bacillus Calmette-Guerin. J. Urol., 135, , 1986.

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