EFFECT OF INTRAVESICAL BACILLUS CALMETTE-GUERIN 813

between Datients who will benefit from treatment and those Case 3. A 93-vear-old woman was treated with 4 transure- thrai-resections i f the bladder during a 10-month period. There were more than 25 tumors at the last resection, leaving no part of the bladder tumor-free, and the histopathological examina- tion showed broad and deep lamina propria invasion of a World Health Organization grade 111 tumor, but no muscularis was present. Random biopsies were not taken and it was not known whether she had carcinoma in situ or not. The patient suffered from severe urgency and had to void every hour day and night during the last 6 months. She was treated with 6 weekly BCG instillations followed by 1 monthly instillation for 15 months. After the start of BCG treatment, the tumors recurred in the right side wall only. Perivesical fat invasion was confirmed 7 months aRer the first BCG instillation. The BCG treatment, however, was continued because micturition improved further and she could hold urine for up to 4 hours. The improvement lasted for 19 months. Her condition deteriorated and the BCG treatment was withdrawn. She had uremia, was treated with a pyelostomy catheter and died 25 months a h r the first BCG instillation.

Case 4 . A 76-year-old man was treated with transurethral resection of the bladder for a World Health Organization grade 111 stage T4b carcinoma with a silent right kidney. Random biopsies were not taken and it was not known whether he had carcinoma in situ or not. He had urgency and frequent voiding and was offered and given BCG. Ten days after the first and only BCG instillation, flank pain and anuria developed and a left pyelostomy catheter was in- serted. The ureteral obstruction persisted and he died of generalized disease 7 months after the instillation.

DISCUSSION

Before we started to treat patients with BCG with pallia- tive intent, we assumed that the cause of the severe urgency and frequency was the carcinoma in situ and not the deeply invasive tumor. Later, the impression at the cystoscopies was that BCG had a n effect on the mucosa with carcinoma in situ but that it did not influence the muscle invasive tumors. Random mucosal biopsies were not taken because of the poor general condition of the patients, but it would have been interesting to learn whether the mucosa still showed carci- noma in situ or not in the 2 patients in whom it was diag- nosed before BCG therapy.

Three patients were very satisfied with the BCG treat- ment, in that they noted a gradual a n d significant improve- ment in micturition after 3 to 4 instillations. This was not different from what is reported after BCG treatment by many other patients with irritative bladder symptoms but without remaining invasive tumor.

Patient 4 was only given 1 instillation because uremia developed. One possible explanation may be that BCG in- creased the bladder wall edema a n d brought forward the ureteral occlusion. Excretory urography immediately before treatment might have been of value.

The low dose of BCG and the short time tha t the solution was retained in the bladder probably contributed to the lim- ited side effects, which were well tolerated, although all patients had increased urgency and frequency for 1 to 2 days after each instillation. Like other patients treated with BCG in our department, the patients were treated with monthly instillations after the initial 6-week induction course, we cannot determine whether this was of value or not. The temporary and acceptable side effects after BCG treatment should be compared with the side effects of a short course of pelvic radiotherapy, which may affect bladder and intestine and may occasionally be fatal.'

CONCLUSIONS

The results of the palliative BCG treatment were encour- aging, but further experience is necessary to discriminate

who will not. One possible explanation of the improvement in local symptoms is that BCG also has effect on coexistent carci- noma in situ in bladders with advanced. unresectable disease.

REFERENCES

1. Lamm, D. L.: BCG in perspective: Advances in the treatment of superficial bladder cancer. Eur. Urol., suppl. 1, 27: 2, 1995.

2. Holmang, S. and Borghede, G.: Early complications and survival following short-term palliative radiotherapy in invasive blad- der carcinoma. J. Urol., 155: 100, 1996.

3. Holmang, S., Hedelin, H., Borghede, G. and Johansson, S. L.: Long-term follow-up of a bladder carcinoma cohort: Question- able value of radical radiotherapy. J. Urol., 157: 1642, 1997.

4. Gospodarowicz, M. K. and Warde, P.: The role of radiation ther- apy in the management of transitional cell carcinoma of the bladder. Hematol./Oncol. Clinics N. Amer., 6 147, 1992.

5. Green, N. and George, F. W. 111.: Radiotherapy of advanced localized bladder cancer. J. Urol., 111: 611, 1974.

6. Rosenbaum, R. S., Park, M. C. and Fleischmann, J.: Intravesical bacille Calmette-Guerin therapy for muscle invasive bladder cancer. Urology, 47: 208, 1996.

7. Morales, A,, Nickel, J . C. and Wilson, J. W. L.: Dose-response of bacillus Calmette-Guerin in the treatment of superficial blad- der cancer. J . Urol., 147: 1256, 1992.

EDITORIAL COMMENT

The toxicity of BCG has been emphasized and reviewed in detail,' but the important observation in this paper, that BCG immunother- apy can effectively reduce the irritative symptoms associated with transitional cell carcinoma, has been largely ignored. It should be stated clearly that BCG is not appropriate treatment for patients with muscle invasive tumors for whom such accepted options as radical cystectomy, radiation therapy or systemic chemotherapy combined with surgery or radiation are available. However, BCG immunotherapy is fully appropriate in patients who have no other options and may result in therapeutic as well as palliative effects. The response to BCG is not necessarily limited to tumors confined to the urothelium or lamina propria but is limited by tumor volume and the ability of the organism to come in contact with tumor cells. Complete (or as nearly complete as possible) transurethral resection is therefore recommended.

I have not recommended dose reduction in patients who are elderly or debilitated, because we have not identified reliable prognostic indicators for patients who will have increased toxicity or reduced immune response to BCG. However, in patients who do have in- creased side effects, reduction of the dose of BCG to one-half and adding 300 mg. of isoniazid are beneficial. It should be noted that published reports have failed to show an advantage of monthly maintenance BCG,Z but 3 weekly maintenance doses at 3 months, 6 months and then every 6 months significantly reduces tumor recur- rence? and disease progression.'

Donald L. Lamm Department of Urology West Virginia University Morgan tou! n , West Virginia

1. Lamm. D. L.: Complications of Bacillus Calmette-Guerin immu- notherapy. Urol. Clin. N. Amer., 1 9 3, 565, 1992.

2. Badalament, R. A., Herr, H. W., Wong, G. Y., et al: A prospective randomized trial of maintenance versus nonmaintenance in- travesical Bacillus Calmette-Guerin therapy of superficial bladder cancer. J . Clin. Oncol., 5: 441, 1987.

3. Lamm, D. L., Crawford, E. D., Blumenstein, B., Crissman, J., deVere White, R., Wolf, M.. Lowe, B., Sarosdy. M., Schellhammer. P., Sagalowsky, A,, Smith, J., Grossman, H. B., Smith, J. A., Beck, T. M., Leimert, J. and Coltman, C. A,: Maintenance BCG immunotherapy of superficial bladder can- cer: A randomized prospective southwest oncology group study. J . Urol., part 2, 147: 242, 1992.

4. Lamm, D. L., Blumenstein, B., Sarosdy, M., Grossman, B. and Crawford, D.: Significant long-term benefit with BCG mainte- nance therapy: A southwest oncology group study. J. Urol., 157: 4(A). 831, 1997.