Correspondence
Use of Statins and Outcome of BCG Treatment for Bladder Cancer
N Engl J Med 2006; 355:2705-2707December 21, 2006
- Article
To the Editor:
The intravesical administration of bacille Calmette–Guérin (BCG) vaccine for high-risk, non–muscle-invasive bladder cancer and carcinoma in situ is one of the most successful immunotherapies to date.1 Studies in animals have shown that the generation of effector cells, called BCG-activated killer cells, depends on type 1 helper T (Th1)–type cytokines.2 In humans, a high Th1-biased urinary cytokine profile after several weekly intravesical instillations of BCG correlates with a better clinical response.3
Statins have cholesterol-lowering properties and also immunomodulating actions. Several reports have indicated that statins can induce antiinflammatory type 2 helper T (Th2)–type cytokines (interleukin-4, interleukin-5, and interleukin-10) and inhibit the secretion of interleukin-2, interleukin-12, interferon gamma, and tumor necrosis factor through the inhibition of signal transducer and activator of transcription 4 (STAT4) and the transcription factor T-bet. The result is strong attenuation of the Th1-type immune response and promotion of the development of Th2 cells.4,5
We retrospectively analyzed the clinical outcomes for 84 patients who had received BCG immunotherapy for the treatment of non–muscle-invasive bladder cancer; 19 of the patients had taken statins during BCG immunotherapy, and 65 had not (Table 1Table 1
Baseline Characteristics of the Patients.). We determined the number of recurrences during the first year, the number of total recurrences, tumor progression, the time to cystectomy, and the time to the development of distant metastases. The two groups had similar medical histories, follow-up times, and pathological features.The median follow-up was 46 months. The number of recurrences during the first year or subsequent years did not differ significantly between the groups. However, in 53% of the patients who took statins, the tumor became more aggressive, whereas this change occurred in only 18% of the patients who did not take statins (P=0.004; odds ratio, 4.9; 95% confidence interval [CI], 1.64 to 14.69). Similarly, 42% of the patients in the statin group had to undergo radical cystectomy, as compared with only 14% of the patients who did not take statins (P=0.01; odds ratio, 4.5; 95% CI, 1.43 to 14.30). Among the patients who underwent radical cystectomy, the number in whom metastases developed and the time to their development were similar in the two groups.
Our observations suggest that the discontinuation of statin therapy during BCG immunotherapy might improve the clinical outcome, since the use of statins was significantly associated with an increased risk of tumor progression and a subsequent need for radical cystectomy.
5 ReferencesPaul Hoffmann, M.D.
Jules Bordet Institute, 1000 Brussels, Belgium
pahoffma@ulb.ac. be Thierry Roumeguère, M.D.
Claude Schulman, M.D., Ph.D.
Erasme Hospital, 1070 Brussels, BelgiumRoland van Velthoven, M.D., Ph.D.
Jules Bordet Institute, 1000 Brussels, Belgium1
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- Citing Articles (19)
Citing Articles
1
U. Ravnskov, K. S. McCully, P. J. Rosch. (2011) The statin-low cholesterol-cancer conundrum. QJM
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David Margel, Sultan S. Alkhateeb, Antonio Finelli, Neil Fleshner. (2011) Diminished Efficacy of Bacille Calmette-Guérin Among Elderly Patients with Nonmuscle Invasive Bladder Cancer. Urology 78:4, 848-854
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In Hae Park, Jin Young Kim, Ji Young Choi, Ji-Youn Han. (2011) Simvastatin enhances irinotecan-induced apoptosis in human non-small cell lung cancer cells by inhibition of proteasome activity. Investigational New Drugs 29:5, 883-890
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Mark L. Gonzalgo. (2009) Editorial Comment. The Journal of Urology 182:4, 1311-1312
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Ted A. Skolarus, Eugene W. Lee, Katherine S. Virgo, Matthew D. Katz, M'Liss A. Hudson, Adam S. Kibel, Robert L. Grubb. (2009) Intravesical Bacille Calmette-Guérin Therapy for Non-Muscle-Invasive Bladder Cancer: Effects of Concurrent Statin Therapy. Journal of the American College of Surgeons 209:2, 248-253
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Jared Whitson, Anna Berry, Peter Carroll, Badrinath Konety. (2009) A multicolour fluorescence in situ hybridization test predicts recurrence in patients with high-risk superficial bladder tumours undergoing intravesical therapy. BJU International 104:3, 336-339
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Mark R. Goldstein, Luca Mascitelli, Francesca Pezzetta. (2009) The double-edged sword of statin immunomodulation. International Journal of Cardiology 135:1, 128-130
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William A. See. (2009) Commentary on An analysis of the effect of statin use on the efficacy of bacillus Calmette-Guerin treatment for transitional cell carcinoma of the bladder. Urologic Oncology: Seminars and Original Investigations 27:3, 340-341
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Chung–Jyi Tsai, Michael F. Leitzmann, Walter C. Willett, Edward L. Giovannucci. (2009) Statin Use and the Risk of Cholecystectomy in Women. Gastroenterology 136:5, 1593-1600
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Mark R. Goldstein, Luca Mascitelli, Francesca Pezzetta. (2009) Statins, regulatory T cells, and pediatric graft coronary artery disease. Pediatric Transplantation 13:1, 139-140
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Marek Jakobisiak, Jakub Golab. (2009) Statins can modulate effectiveness of antitumor therapeutic modalities. Medicinal Research Reviewsn/a-n/a
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Ryan K. Berglund, Caroline J. Savage, Kinjal C. Vora, Jordan M. Kurta, Angel M. Cronin. (2008) An Analysis of the Effect of Statin Use on the Efficacy of Bacillus Calmette-Guerin Treatment for Transitional Cell Carcinoma of the Bladder. The Journal of Urology 180:4, 1297-1300
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Mark R. Goldstein, Luca Mascitelli, Francesca Pezzetta. (2008) Re: Khurana et al.: Statins Might Reduce Risk of Renal Cell Carcinoma in Humans: Case-Control Study of 500 000 Veterans (Urology 2008;71:118-122). Urology 72:3, 717
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Vikas Khurana, Gloria Caldito, Murali Ankem. (2008) Reply by the Authors. Urology 72:3, 717-718
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M. R. Goldstein, L. Mascitelli, F. Pezzetta. (2008) Antitumour necrosis factor-alpha treatment, statins, regulatory T cells and tuberculosis. Alimentary Pharmacology & Therapeutics 27:7, 619-619
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Kwang Seok Ahn, Gautam Sethi, Bharat B. Aggarwal. (2008) Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-κB pathway. Biochemical Pharmacology 75:4, 907-913
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Mark R. Goldstein, Luca Mascitelli, Francesca Pezzetta. (2008) Statins, Tregs and cancer. Atherosclerosis 196:1, 483-484
CrossRef18
(2007) Statins and the Effect of BCG on Bladder Cancer. New England Journal of Medicine 356:12, 1276-1277
Full Text19
A.S. Kibel. (2007) Use of Statins and Outcome of BCG Treatment for Bladder Cancer. Yearbook of Urology 2007, 135-136
CrossRef
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