Introduction: Primary carcinoma in situ (P-CIS) of the bladder is rare and its clinical behavior and predictive features have not been well described. The purpose of this study was to evaluate the effects of various factors including angiotensin-2 converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) on recurrence-free survival (RFS)-related prognosis in patients with P-CIS. Materials and Methods: In our medical center, 5,945 patients were diagnosed with bladder cancer from January 1999 to January 2014. Of these, 64 patients were diagnosed with CIS and were treated with at least 6 cycles of Bacillus Calmette-Guérin (BCG). We accessed variables including patient age, sex, initial presenting symptoms, smoking history, P-CIS descriptions, urine cytology, and medication history related to hypertension. Results and Conclusions: We evaluated the use of anti-hypertensive medications (ACEIs/ARBs, p = 0.028), the symptom of non-gross hematuria (p = 0.028), and older age (p = 0.015) as significant factors related to RFS. Older age was also a significant factor for influencing the RFS rate. We found that the use of anti-hypertensive medications (ACEIs/ARBs) improves RFS in patients with P-CIS after BCG therapy. The prognosis was poor when there was no gross hematuria and if patients were at older ages at the time of diagnosis of P-CIS.

1.
Lamm DL: Carcinoma in situ. Urol Clin North Am 1992; 19: 499–508.
2.
Morales A, Eidinger D, Bruce AW: Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976; 116: 180–183.
3.
Sylvester RJ, van der MA, 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.
4.
Sylvester RJ, van der Meijden A, Witjes JA, Jakse G, Nonomura N, Cheng C, Torres A, Watson R, Kurth KH: High-grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urol 2005; 66: 90–107.
5.
O’Donnell MA: Advances in the management of superficial bladder cancer. Semin Oncol 2007; 34: 85–97.
6.
Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BW, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R: EAU Guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447–461.
7.
Witjes JA, Palou J, Soloway M, Lamm D, Kamat AM, Brausi M, Persad R, Buckley R, Colombel M, Böhle A: Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of Bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS). BJU Int 2017; 112: 742–750.
8.
Chade DC, Shariat SF, Adamy A, Bochner BH, Donat SM, Herr HW, Dalbagni G: Clinical outcome of primary versus secondary bladder carcinoma in situ. J Urol 2010; 184: 464–469.
9.
Nadler RB, Catalona WJ, Hudson MA, Ratliff TL: Durability of the tumor-free response for intravesical Bacillus Calmette-Guerin therapy. J Urol 1994; 152: 367–373.
10.
Solsona E, Iborra I, Dumont R, Rubio-Briones J, Casanova J, Almenar S: The 3-month clinical response to intravesical therapy as a predictive factor for progression in patients with high risk superficial bladder cancer. J Urol 2000; 164: 685–689.
11.
van Gils-Gielen RJ, Witjes WP, Caris CT, Debruyne FM, Witjes JA, Oosterhof GO: Risk factors in carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group. Urology 1995; 45: 581–586.
12.
Herr HW, Dalbagni G: Defining Bacillus Calmette-Guerin refractory superficial bladder tumors. J Urol 2003; 169: 1706–1708.
13.
Shirotake S, Miyajima A, Kosaka T, Tanaka N, Maeda T, Kikuchi E, Oya M: Angiotensin II type 1 receptor expression and microvessel density in human bladder cancer. Urol 2011; 77: 1009.e1019–e1025.
14.
Tanaka N, Miyajima A, Kosaka T, Shirotake S, Hasegawa M, Kikuchi E, Oya M: 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: 2982–2992.
15.
Blute ML, Jr., Rushmer TJ, Shi F, Fuller BJ, Abel EJ, Jarrard DF, Downs TM: Renin-angiotensin inhibitors decrease recurrence after transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer. J Urol 2015; 194: 1214–1219.
16.
Yuge K, Miyajima A, Tanaka N, Shirotake S, Kosaka T, Kikuchi E, Oya M: Prognostic value of renin-angiotensin system blockade in non-muscle-invasive bladder cancer. Ann Surg Oncol 2012; 19: 3987–3993.
17.
Montironi R, Lopez-Beltran A: The 2004 WHO classification of bladder tumors: a summary and commentary. Int J Surg Pathol 2005; 13: 143–153.
18.
Juillerat-Jeanneret L, Celerier J, Chapuis Bernasconi C, Nguyen G, Wostl W, Maerki HP, Janzer RC, Corvol P, Gasc JM: Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. Br J Cancer 2004; 90: 1059–1068.
19.
De Paepe B, Verstraeten VL, De Potter CR, Vakaet LA, Bullock GR: Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma. Histochem Cell Biol 2011; 116: 247–254.
20.
Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, MacKinnon PL, Meredith PA, Murray LS, Reid JL, Robertson JW: Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 1998; 352: 179–184.
21.
Tanaka N, Miyajima A, Kikuchi E, Matsumoto K, Hagiwara M, Ide H, Kosaka T, Masuda T, Nakamura S, Oya M: Prognonstic impact of renin-angiotensin system blockade in localised upper-tract urothelial carcinoma. Br J Cancer 2012; 106: 290–296.
22.
Hudson MA, Herr HW: Carcinoma in situ of the bladder. J Urol 1995; 153: 564–572.
23.
Singh R, Saleemi A, Walsh K, Popert R, O’Brien T: Near misses in bladder cancer – an airline safety approach to urology. Ann Royal Coll Surg Eng 2003; 85: 378–381.
24.
Rink M, Xylinas E, Babjuk M, Pycha A, Karakiewicz PI, Novara G, Dahlem R, Shariat SF: Smoking reduces the efficacy of intravesical Bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer. Eur Urol 2012; 62: 1204–1206.
25.
Santos F, Dragomir A, Kassouf W, Franco E, Aprikian A: Urologist referral delay and its impact on survival after radical cystectomy for bladder cancer. Curr Oncol 2015; 22:e20–e26.
26.
Lammers RJ, Witjes WP, Hendricksen K, Caris CT, Janzing-Pastors MH, Witjes JA: Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer. Eur Urol 2011; 60: 713–720.
27.
Sopori M: Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2: 372–377.
28.
Gofrit ON, Pode D, Pizov G, Zorn KC, Katz R, Duvdevani M, Shapiro A: The natural history of bladder carcinoma in situ after initial response to Bacillus Calmette-Guerin immunotherapy. Urol Oncol 2009; 27: 258–262.
29.
Nieder AM, Brausi M, Lamm D, O’Donnell M, Tomita K, Woo H, Jewett MA: Management of stage T1 tumors of the bladder: international consensus p. Urology 2005; 66: 108–125.
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