Nicholas F. Viek

Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin.

We evaluated 155 patients with superficial bladder cancers (Stages Ta, T1, and TIS) and treated them with either intravesical bacillus Calmette-Guérin (Tice strain) (BCG) or doxorubicin hydrochloride (Adriamycin), in a multicenter nonrandomized study. At present 140 of these patients in treatment Groups I and II are being followed up. With additional follow-up, BCG continued to produce a higher percentage of complete remissions (71%) than doxorubicin (54%). The percentage of incomplete remission with BCG (7%) was half that with doxorubicin (14%). Half of the patients whose initial therapy failed had complete remission after additional therapy. However, for patients with recurrence, additional follow-up shows a recurrence rate per 100 patient-months for BCG (1.0) only slightly lower than that for doxorubicin (1.1). The percentage of progressions continued to be higher with BCG (8.5%) than with doxorubicin (5%), but the difference between these results for the two drugs proved slightly less than we reported previously. Of the patients in this study, 2.5 percent (all treated with BCG) required cystectomy. A comparison of the results of our study with those of 13 other studies using BCG to treat bladder cancer indicates that therapy beyond an initial course of 6 weekly treatments increases the percentage of complete response. All of the studies showed that the greatest improvement in percentage of complete response occurred with the second course of treatment. The value of maintenance therapy cannot yet be determined, since few studies have used that protocol. The percentage of patients requiring cystectomy in studies with fewer than 20 treatments was 2.2 times higher than in studies with more than 20 treatments.

Does bacillus Calmette-Guérin immunotherapy accelerate growth and cause metastatic spread of second primary malignancy?

In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus Calmette-Guérin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of BCG therapy. All 5 showed acceleration of the second primary tumor, and distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spread. Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. We have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of BCG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered.

Superficial bladder cancer treated with intravesical bacillus calmette-guérin or adriamycin: follow-up report

We evaluated 139 patients with superficial bladder cancer (Stages Ta, Tl, and TIS) and treated them with either intravesical bacillus Calmette-Guérin, Tice strain (BCG), or doxorubicin hydrochloride (Adriamycin [ADR]) in a nonrandomized, multicenter study. Our follow-up study comprises 135 of these patients. Of these patients, 78 tumors were completely resected, and 61 were incompletely resected. When a proportional-hazards model (Cox) was applied, there was a statistically significant difference between the recurrence rates for the two drugs. On the basis of recurrence rates per 100 patient-months, both BCG (1.2) and ADR (0.9) worked well with completely resected tumors. However, for incomplete resections, the recurrence rate for BCG (0.9) was less than half that for ADR (1.9). The overall recurrence rates were 1.1 and 1.3 for BCG and ADR, respectively. There have been 42 failures of treatment with either BCG or ADR. We defined failure as any recurrence of tumor; progression of the cancer in stage, grade, tumor number or size; or any residual tumor after 18 treatments (14 months of therapy). As to the failures in patients whom we followed up, and whose treatment was either switched from ADR to BCG or continued on further BCG treatment, 53 per cent have achieved complete remission. Complete remission for BCG and ADR were 76 per cent and 52 per cent, respectively. Of the various factors considered in the study, only tumor grade and treatment drug were statistically significant. The cystectomy rate was 1 per cent for BCG-treated patients and 0 for ADR-treated patients.