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MICROWAVE HYPERTHERMIA AND CHEMOTHERAPY FOR BLADDER TUMORS 787
ation therapy and selected anticancer drugs in locally advanced human malignancies. Int. J. Hyperthermia, 4: 143, 1988.
22. Hall, H. H., Schade, R. 0. K and Swinny, J.: Effect of hyperthermia on bladder cancer. Brit. Med. J., 2 593, 1974.
23. Hall, R. R., Wadehra, V., Towler, J. M., Hindmarsh, J. R. and Byrne, P. 0.: Hyperthemia in the treatment of bladder tumors. Brit. J. Urol., 48: 603, 1976.
24. Ludgate, C. M., McLean, N., Carswell, G. F., Newsam, J. E., Pettigrew, R. T. and Tulloch, W. S.: Hyperthermic perfusion of the distended bladder in the management of recurrent transitional cell carcinoma. Brit. J. Urol., 47: 841, 1975.
25. England, H. R., Anderson, J. D., Minasian, H., Marshall, V. R., Molland, E. A. and Blandy, J. P.: The therapeutic application of hyperthermia in the bladder. Brit. J. Urol., 47: 849, 1976.
26. Nishimura, K., Ogawa, O., Yoshimura, N., Nakagawa, T. and Sasaki, M.: Effect of hyperthermic irrigation with bleomycin on prophylaxis of recurrence of bladder cancer. Hinyokika Kiyo, 31: 769, 1985.
27. Nakajima, K., Hisazumi, H., Kumaki, 0. and Ueki, 0.: Inhibition of cell growth by irradiation in combination with hyperthermia or anticancer drugs. Acta Rad. Onml., 2 2 487, 1983.
28. Nakajima, K., Hisazumi, H., Misaki, T., Kawaguchi, K, Sugata, T., Kameda. K., Ueki, 0.. Miyagi, T. and Nishino, A,: A hyperthermic perfusion therapy using peplomycin and ethanol for bladder cancer. Hinyokika Kiyo, 30: 1421, 1984.
29. Van der Meijden, A. P. M., Hall, R. R., Pavone-Macaluso, M., Pawinsky, A., Sylvester, R. and Van Glabbeke, M.: Marker tumor response to the sequential combination of intravesical therapy with mitomycin C and BCG-RIVM in multiple superficial bladder tumors. Report from the European Organisation for Research and Treatment of Cancer Genitu urinary Group (EORTC 30897). Eur. Urol., 29: 199,1996.
30. Braken, R. B., Swanson. D. A., Johnoson, D. E., De Furia, D., Eschenbach, A. C. and Crooke, S.: Role of intravesical mitomycin C in management of superficial bladder tumors. Urology, 16 11, 1980.
31. Bouffioux, C., van der Meijden, A,, Kurth, K H., Jakse, G., Bono, A, Hall, R., Oosterling, W. and Sylvester, R.: Objective response of superficial bladder tumors to intravesical treatment (including review of response of marker lesions). In: European Organisation for Research and Treatment of Cancer Genitourinary Gmup Monographe 11: Recent Progress in Blad- der and Kidney Cancer. New York Wiley-Liss, Inc., pp. 29-42.1992.
32. Richie, J. P.: Intravesical chemotherapy, treatment selection, techniques and results. Urol. Clin. N. Amer., 19: 521, 1992.
33. Maffezzini, M., Simonato, A,, Zanon, M., Raber, M. and Carmignani, R.: Up-front intravesical chemotherapy for low stage, low grade recurrent bladder cancer. J. Urol., 155: 91, 1996.
34. Jauhianen, K., Kangas, L., Kapyla, H. and Alfthan, 0.: Intravesical cyto- statics: pH-dependence of antitumor activity. Urol. Res., 1 3 19, 1985.
35. Wientjes, M. G., Badalament, R. A. and Au, J. L.-S.: Use of pharmacolog- ical data and computer simulations to design an efficacy trial of intra vesical mitomycin C therapy for superficial bladder cancer. Cancer Chemother. Pharmacol., 3 2 255, 1993.
36. Dalton, J. T., Wientjes, M. G., Badalament. R. A,, Drago, J. R. and Au, J. L.-S.: Pharmacokinetics of intravesical mitomycin C in superficial bladder cancer. Cancer Res., 51: 5144, 1991.
37. Wientjes, M. G., Badalament, R. A,, Hassan. F., Drago, J. R. and Au, J. L.S.: Factors influencing bladder wall concentration during i n h v w i d cancer chemotherapy. F’roc. Amer. Ass. Cancer Res., 33: 556,1992.
38. Watanabe, H., Nako, M., Nakagawa, S. and Takada, H.: Size and location of tumors influencing the effect of bladder instillation therapy. Cancer Chemother. Pharmacol., 20: 349. 1987.
39. Huland, H., Kloppel, G., Feddersen, I., Otto, U., Brachmann. W., Hubmann, H., Kautinann, J., Knipper, W., Lantzius-Beninga, F. and Huland, E.: Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final eval- uation of a prospective multicentric study with 419 patients. J. Urol., 144: 1107, 1990.
40. Isaka, S., Okano, T., Shimazaki, J., Igarashi. T., Marakami. S., Higa, T., Ishikawa, T., Zama, S., Kataumi, S. and Kataumi, Z.: Rophylaxis of superficial bladder cancer with instillation of adriamycin or mitomycin C. Cancer Chemother. Pharmacol., 20: 77, 1987.
41. Matzkin, H., Rangel, M. C. and Soloway, M. S.: In vitro study of the effect of hyperthermia on normal bladder line and on five different transi- tional cell carcinoma cell lines. J. Urol., 147: 1671, 1992.
This study evaluates the role of microwave hyperthermia and intravesical mitomycin C for recurrent superficial transitional cell
1 carcinoma of the bladder no longer amenable to transurethral resec- I
1 tion due to extent of disease. This group, which represents a small minority (approximately 1 to 3%) of patients with bladder cancer, has traditionally been treated with radical cystectomy because treat- ment options have been limited.
All 19 patients in this series had extensive disease involving greater than 30% of the bladder wall that was judged to be unresectable. After the &week course of therapy initial followup biopsies were negative in 9 patients (47%) and in 7 with residual disease transurethral resection was believed to be feasible. Overall only 3 patients required radical cystectamy. Ofthe 16 responders disease recurred in 8 and the authors state that there was no evidence of tumor progression.
Unfortunately th is study leaves many questions unanswered. Most importantly, the study populations are not well defined. It is not clear how many patients had stage TA versus T1 disease at therapy and how many had associated carcinoma in situ. One does not have a clear conception of the risk of recurrence and progression without these data. In addition, the main entry and response crite- rion (whether transurethral resection was feasible before or after therapy) is too subjective. One oRen finds that transurethral resec- tion of a bladder tumor can be performed with some effort in such patients, although staged procedures may be required. The morbid- ity of treatment is also incompletely defined. One wonders how patients would rate discomfort, since tissue sloughing was noted in many and irritative voiding symptoms were common. Another issue is the cost of therapy because advanced technology is required for therapy administration. This issue may be particularly relevant, since startup costs could be substantial and the number of patients who would qualfy for treatment would be relatively small.
I certainly agree with the authors that a well designed, prospec- tive, randomized trial is needed to establish the efficacy of this treatment protocol. Such a trial would ideally control for the effect of intravesical therapy alone, incorporate more objective response cri- teria and include routine questionnaires to evaluate patient percep- tion of treatment related morbidity.
Steven C. Campbell Department of Urology Northwestern University Medical School Chicago, Illinois
REPLY BY AUTHORS
Due to the large number of tumors and superficial extension on the bladder surface, it was not possible tn define how many patients had stage TA versus T1 disease and how many had carcinoma in situ. Nevertheless it is clearly reported that all patients had at least 1 stage T1 recurrence following standard chemoprophylaxis or immunoprophy- laxis and they had undergone at least 2 resections before entering the study with an average disease-free interval of 5 months. We agree that the entry and response criteria were subjective, and that transient macroscopic complete resection of m u l t i f d bladder tumors often can be obtained by staged transurethd procedures in such patients but we do not consider this a valid alternative to radical cystectomy. Moreover, no more than 3 residual tumors of a large and not precisely definitive primitive number were present in those patients defined as partial responders. Treatment morbidity was evaluated and compared to stan- dard treatment with intravesical mitomycin C in a previous study (reference 10 in article) using questionnaires to evaluate patient per- ception of treatment and related morbidity.
Therapy cost (mainly start-up costs) although not yet precisely defined, is a relevant issue. We believe that the combination of local hyperthermia and intravesical chemotherapy using the SB-TS 101 system also can be economically competitive with repeat transure- thral resections of bladder tumors or radical cystectomy. Treatment of this rare subset of patients with superficial bladder cancer is one but not the only field of application of local hyperthermia and che- motherapy. Results of larger series treated in a neoadjuvant setting have been reported previously (references 9 and 10 in article). A randomized multicenter study is ongoing to establish the effects of this treatment as prophylaxis of bladder tumor recurrence.l Prelim- inary results are exciting and, if confirmed, the indications for such novel therapy could be extended to a large number of patients as prophylaxis of high risk superficial bladder tumors.
1. Leib, Z., Baniel, J., Servadio, C., Colombo, R., Da Pozzo. L. F., Lev, A., Rigatti. P., Caldarera. E. and Pavone Macaluso, M.: Mitomycin C (MMC) vs. MMC combined with local microwave hyperthermia (LMWH) 88 prophylaxis of recurrence of superficial transitional blad- der cancer. a preliminary report. Eur. Urol., suppl. 2, So: 7254 a b stract, 198, 1996.