Recurrence, Progression and Success in Stage Ta Grade 3 Bladder Tumors Treated With Low Dose Bacillus Calmette-Guerin Instillations

Lebrét, Thierry; Bohin, Denis; Kassardjian, Z; Hervé, Jean-Marie; Molinié, Vincent; Barré, Philippe; Lugagne, Pierre-Marie; Botto, Henry

doi:10.1097/00005392-200001000-00016

Cited by 14 publications

(17 citation statements)

References 28 publications

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“…14 In an effort to reduce the potential for complications, some reports have demonstrated sufficient efficacy using a lower dose of BCG. [1][2][3][4][5][6][7][8][9] In these previous studies, the dosedependent response of BCG instillation has not been clearly shown, but lower incidence of adverse effects has been clearly demonstrated.…”

Section: Discussionmentioning

confidence: 93%

“…Numerous investigations have been conducted regarding the doses and duration of BCG instillation for improving efficacy and reducing adverse effects. [1][2][3][4][5][6][7][8][9] Several commercially available BCG strains have been adopted for this treatment and it has been reported that the suitable dose of each strain might be different. [10][11][12] The therapeutic efficacy of BCG is related in part to the titer, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low‐dose bacillus Calmette‐Guérin for superficial bladder cancer recurrence

et al. 2003

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Background : Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. Methods : A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. Results : BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups ( P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. Conclusion : Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low‐dose bacillus Calmette‐Guérin for superficial bladder cancer recurrence

et al. 2003

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“…Zlotta et al examined HSP60 expression during the humoral response stimulated by BCG in the treatment of patients with superficial bladder carcinoma. Intravesical BCG therapy is accepted as the treatment of choice for patients with noninvasive bladder tumors who have a high risk of recurrence 28–30. BCG therapy uses the Mycobacterium bovis , which contains a very immunogenic protein: HSP60 (65 kD).…”

Section: Discussionmentioning

confidence: 99%

Heat shock proteins HSP27, HSP60, HSP70, and HSP90

Lebrét

Watson

Molinié

et al. 2003

Cancer

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149

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BACKGROUND Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in neoplasia has been implicated in the regulation of apoptosis, and HSPs also can act by increasing immunity. In the current study, the authors attempted to clarify the significance of HSPs in bladder carcinoma and their effect on tumor behavior. METHODS Expression levels of the 27‐kilodalton HSP (HSP27), HSP60, HSP70, and HSP90 were studied using immunohistochemistry on tissue sections from 42 transitional cell carcinomas of the bladder (14 Grade 1 tumors; 13 Grade 2 tumors; 15 Grade 3 tumors, including 3 tumors associated with carcinoma in situ; 30 Stage Ta tumors; 7 Stage T1 tumors; and 5 Stage T2 tumors). Bladder specimens from 10 healthy patients were used as controls in the study. The selected patients had a mean follow‐up of 52 months (range, 24–78 months). Among the 37 patients with superficial bladder carcinoma, 17 patients did not have any recurrence after undergoing primary resection, and 20 patients developed recurrent disease, including 4 recurrences with muscle invasion. HSP expression was evaluated according to the percentage of positively stained cells, and loss of expression was defined as < 80% of stained cells. RESULTS In normal bladder specimens, all four HSPs (HSP27, HSP60, HSP70, and HSP90) were expressed strongly in the cytoplasm and membrane from the basal cell layer to the superficial cell layer. Loss of expression was detected in tumors: respectively, 45.2%, 38.1%, 69.0% and 23.8% of tumors showed a loss of immunostaining for HSP27, HSP60, HSP70, and HSP90. No correlation between HSP expression and grade was found. Low expression levels of HSP27 and HSP60 were correlated with higher tumor stage (87% vs. 6% [P < 0.001] and 78% vs. 9% [P < 0.01], respectively). HSP60 and HSP90 expression levels were correlated with final outcome for patients with superficial bladder carcinoma: loss of expression was associated with the risk of developing an infiltrating recurrence (97% vs. 6.0% [P < 0.001] and 88.2% vs. 52.5% [P = 0.02] for HSP60 and HSP90, respectively). CONCLUSIONS HSPs were expressed in normal urothelium, and the current results indicated that loss of HSP60 and HSP90 expression may have prognostic relevance in patients with bladder carcinoma. The authors believe that HSP60 may be a very useful marker for patients with superficial bladder carcinoma and may be used for predicting disease progression. If these data are confirmed, low HSP60 expression levels may be usable as a prognostic marker to identify patients for whom local treatment would be insufficient. Cancer 2003;98:970–7. © 2003 American Cancer Society. DOI 10.1002/cncr.11594

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“…The finding of urothelial carcinoma by urine cytology has the greatest implications after TUR or during BCG treatment, but one study found an association between pre-treatment cytology and BCG response, as well as progression [60]. In this way, it might be a surrogate marker for overall high-risk disease, including CIS.…”

Section: Groups At Risk Of Failure (Lowest Level Of Evidence)mentioning

confidence: 99%