Correspondence
Statins and the Effect of BCG on Bladder Cancer
N Engl J Med 2007; 356:1276-1277March 22, 2007
- Article
To the Editor:
Hoffmann and colleagues (Dec. 21 issue)1 report on the use of statins and the outcome of immunotherapy with bacille Calmette–Guérin (BCG) vaccine in 84 patients with superficial bladder cancer. The authors report that over a median follow-up period of 46 months, 19 patients who were using statins had an increased risk of “more aggressive” disease.
We analyzed outcomes in a cohort of 156 patients (median follow-up, 56 months) who received BCG; 39 used statins during the treatment, and 117 did not. We found no significant differences between the two groups in the incidence of tumor recurrence (59% in both groups, P=0.80), the incidence of tumor progression (30% and 28%, respectively; P=0.57), or the number of deaths. Since the proposed immunomodulatory role of statins1 might be more relevant in patients receiving maintenance therapy,2 we performed a subgroup analysis of data from patients receiving only induction BCG therapy, as compared with those receiving BCG as both induction and maintenance therapy. We still found no effect of the use of statins. Our data do not support the authors' conclusion that “discontinuation of statin therapy during BCG immunotherapy might improve the clinical outcome,” especially given the risk of adverse cardiac events associated with withdrawal of statins.3
Ashish M. Kamat, M.D.
Xifeng Wu, Ph.D.
M.D. Anderson Cancer Center, Houston, TX 77030
akamat@mdanderson.org Dr. Kamat reports serving as a panelist at the Global BCG Advisory Group Meeting sponsored by Aventis Pasteur.
3 References1
Hoffmann P ,Roumeguere T ,Schulman C ,van Velthoven R . Use of statins and outcome of BCG treatment for bladder cancer. N Engl J Med 2006;355:2705-2707
Full Text | Web of Science | Medline2
Sylvester RJ ,van der Meijden AP ,Lamm DL . Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-1970
CrossRef | Web of Science | Medline3
Heeschen C ,Hamm CW ,Laufs U ,Snapinn S ,Bohm M ,White HD . Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002;105:1446-1452
CrossRef | Web of Science | Medline
To the Editor:
Hoffmann et al. state that the groups they studied were “similar.” However, a multivariate logistic-regression analysis with adjustment for well-established risk factors in patients with bladder cancer would have better characterized the real contribution of statins in their patients.
Anna Orsola, M.D.
Lluís Cecchini, M.D.
Hospital Vall d'Hebron, 08035 Barcelona, Spain
annaorsola@hotmail.com Joaquim Bellmunt, M.D.
Hospital de Mar, 08003 Barcelona, SpainAuthor/Editor Response
Although Kamat and Wu did not find significant differences between patients using statins and those not using statins in a study similar to ours, we believe that the statins can attenuate the immune response of type 1 helper cytokines1 that is involved in the action of BCG.
Orsola and colleagues question our statistical analyses. We were unable to present all our data in our letter to the editor. When patients were enrolled, we assessed age, date of diagnosis of cancer, tumor grade and pathological T-stage category after transurethral resectioning, presence or absence of concomitant carcinoma in situ, number of recurrences during the first year after diagnosis and total number of recurrences, pathological T-stage progression, time to cystectomy, and time to the appearance of distant metastases. We compared the outcomes for patients who were taking statins during BCG immunotherapy and those who were not by using univariate and multivariate logistic-regression analyses that included age and cholesterol level but that were not adjusted for the specific statin, given the small number of patients in the various statin groups. The adjusted odds ratio for older age and progression to more aggressive disease in the statin group was 5.02 (95% confidence interval [CI], 1.66 to 5.02; P=0.004), and the adjusted odds ratio for older age and the need for cystectomy was 4.79 (95% CI, 1.48 to 4.79; P=0.008).
1 ReferencesPaul Hoffmann, M.D.
Jules Bordet Institute, 1000 Brussels, Belgium
pahoffma@ulb.ac. be Thierry Roumeguère, M.D.
Erasme Hospital, 1070 Brussels, BelgiumRoland van Velthoven, M.D., Ph.D.
Jules Bordet Institute, 1000 Brussels, Belgium1
Greenwood J ,Steinman L ,Zamvil SS . Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol 2006;6:358-370
CrossRef | Web of Science | Medline
- Citing Articles (6)
Citing Articles
1
H. Barton Grossman. (2010) Re: Reduced Bladder Cancer Recurrence Rate with Cardioprotective Aspirin After Intravesical Bacille Calmette-Guérin. European Urology 57:6, 1115
CrossRef2
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
CrossRef3
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
CrossRef4
Marek Jakobisiak, Jakub Golab. (2009) Statins can modulate effectiveness of antitumor therapeutic modalities. Medicinal Research Reviewsn/a-n/a
CrossRef5
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
CrossRef6
Vikas Khurana, Gloria Caldito, Murali Ankem. (2008) Reply by the Authors. Urology 72:3, 717-718
CrossRef
