Prognostic Value of Renin–Angiotensin System Blockade in Non-muscle-invasive Bladder Cancer
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To determine whether the administration of renin–angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), affect disease outcome in non-muscle-invasive bladder cancer (NMIBC).
A total of 330 patients with initially diagnosed NMIBC were identified. We retrospectively investigated the clinical outcomes after transurethral resection of bladder tumor (TUR-BT) in patients who did or did not receive RAS inhibitors. The median follow-up period was 4.1 years.
A total of 128 patients (38.8 %) experienced subsequent tumor recurrence, and stage progression was observed in 17 patients (5.2 %) during follow-up. Fifty-one patients (15.5 %) had received ACEI or ARB administration at transurethral resection. Multivariate analysis demonstrated that tumor multiplicity, absence of bacillus Calmette-Guérin instillation, and no administration of ACEI or ARB (P = 0.010, hazard ratio 2.26) were independent risk factors for subsequent tumor recurrence. The 5-year recurrence-free survival rate was 78.4 % in patients administered ACEIs or ARBs, and 53.3 % in their counterparts (P = 0.011).
The absence of RAS inhibitor administration was an independent risk factor for subsequent tumor recurrence in patients with initially diagnosed NMIBC. Our data support further investigation of the role of RAS inhibitors as a potential therapy to decrease tumor recurrence in NMIBC.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49. CrossRef
- Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou-Redorta J. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol. 2008;54:303–14. CrossRef
- Nepple KG, Lightfoot AJ, Rosevear HM, O’Donnell MA, Lamm DL. Bacillus Calmette-Guérin with or without interferon alpha-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer. J Urol. 2010;184:1915–9. CrossRef
- Hall MC, Chang SS, Dalbagni G, et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol. 2007;178:2314–30. CrossRef
- Lamm DL, Blumenstein BA, Crawford ED, et al. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991;325:1205–9. CrossRef
- Sylvester RJ, van der Meijden A, Witjes JA, et al. High-grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urology. 2005;66:90–107. CrossRef
- Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guérin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group study. J Urol. 2000;163:1124–9. CrossRef
- Rivera E, Arrieta O, Guevara P, Duarte-Rojo A, Sotelo J. AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma. Br J Cancer. 2001;85:1396–9. CrossRef
- Egami K, Murohara T, Shimada T, et al. Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth. J Clin Invest. 2003;112:67–75.
- Juillerat-Jeanneret L, Celerier J, Chapuis Bernasconi C, et al. Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. Br J Cancer. 2004;90:1059–68. CrossRef
- George AJ, Thomas WG, Hannan RD. The renin–angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer. 2010;10:745–59. CrossRef
- Miyajima A, Kosaka T, Asano T, Seta K, Kawai T, Hayakawa M. Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis. Cancer Res. 2002;62:4176–9.
- Kosugi M, Miyajima A, Kikuchi E, Horiguchi Y, Murai M. Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer. Clin Cancer Res. 2006;12:2888–93. CrossRef
- Kosaka T, Miyajima A, Takayama E, et al. Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer. Prostate. 2007;67:41–9. CrossRef
- Tanaka N, Miyajima A, Kosaka T, et al. Cis-dichlorodiammineplatinum upregulates angiotensin II type 1 receptors through reactive oxygen species generation and enhances VEGF production in bladder cancer. Mol Cancer Ther. 2010;9:2982–92. CrossRef
- Shirotake S, Miyajima A, Kosaka T, et al. Angiotensin II type 1 receptor expression and microvessel density in human bladder cancer. Urology. 2011;77:1009e19–25.
- Lamm DL, Thor DE, Harris SC, Reyna JA, Stogdill VD, Radwin HM. Bacillus Calmette-Guérin immunotherapy of superficial bladder cancer. J Urol. 1980;124:38–40.
- Malmstrom PU, Wijkstrom H, Lundholm C, Wester K, Busch C, Norlen BJ. 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guérin in patients with superficial bladder carcinoma. Swedish–Norwegian Bladder Cancer Study Group. J Urol. 1999;161:1124–7. CrossRef
- Nieder AM, Brausi M, Lamm D, et al. Management of stage T1 tumors of the bladder. International Consensus Panel. Urology. 2005;66:108–25. CrossRef
- Lever AF, Hole DJ, Gillis CR, et al. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet. 1998;352:179–84. CrossRef
- Wilop S, von Hobe S, Crysandt M, Esser A, Osieka R, Jost E. Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy. J Cancer Res Clin Oncol. 2009;135:1429–35. CrossRef
- Nakai Y, Isayama H, Ijichi H, et al. Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine. Br J Cancer. 2010;103:1644–8. CrossRef
- Yoshiji H, Noguchi R, Toyohara M, et al. Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J Hepatol. 2009;51:315–21. CrossRef
- Crew JP, O’Brien T, Bradburn M, et al. Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Cancer Res. 1997;57:5281–5.
- Santos L, Costa C, Pereira S, et al. Neovascularisation is a prognostic factor of early recurrence in T1/G2 urothelial bladder tumours. Ann Oncol. 2003;14:1419–24. CrossRef
- Szarvas T, Jager T, Totsch M, et al. Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer. Clin Cancer Res. 2008;14:8253–62. CrossRef
- Shirotake S, Miyajima A, Kosaka T, et al. Regulation of monocyte chemoattractant protein-1 through angiotensin II type 1 receptor in prostate cancer. Am J Pathol. 2012;180:1008–16. CrossRef
- Li X, Loberg R, Liao J, et al. A destructive cascade mediated by CCL2 facilitates prostate cancer growth in bone. Cancer Res. 2009;69:1685–92. CrossRef
- Prognostic Value of Renin–Angiotensin System Blockade in Non-muscle-invasive Bladder Cancer
Annals of Surgical Oncology
Volume 19, Issue 12 , pp 3987-3993
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