Can hormone therapy be a part of radical definitive treatment of high-grade bladder cancer patients?
DOI:
https://doi.org/10.11603/2414-4533.2019.3.10550Keywords:
high-grade bladder cancer, surgical treatment, survival, steroid hormone receptorsAbstract
The aim of the work: to determine the difference in high-grade (G3) bladder cancer (BC) morbidity, overall survival after radical surgical treatment depending on the gender of the patients, stage of BC, and to assess the potential impact of hormones on these differences and rationale for hormonal treatment in this disease.
Materials and Methods. We performed retrospective analysis of medical records of 364 G3 BC patients after radical surgical treatment with Kaplan-Meier method to determine correlation between gender, incidence and survival outcomes depending on clinical stage of BC.
Results and Discussion. There were 305 males and 59 females. Overall male/female ratio was 5.2:1. The higher the G3 BC stage, the less diseased females were. Statistically significant difference (p<0.05) between survival curves was detected in patients with Stage IV BCa with better results among females. Overall 5-year survival of patients stage II, III, IV was higher among females. Prior studies point at decrease in expression of androgen receptors and rise in estrogen receptor expression with higher stages of BC. These facts may influence the initiation, progression of BC, and effect of other BC etiological factors.
Conclusions. The female G3 BC patients demonstrate lower incidence and higher survival after surgical treatment than males. The study of expression of sex steroid hormone receptors in G3 BC tissue, efficiency of hormonal treatment to prevent the advance of the disease and improve the survival results after surgical treatment deserves further attention.
References
Fedorenko, Z.P., Mykhayilovych, Yu.Y., Hulak, L.O., Horokh, Ye.L., Ryzhov, A.Yu., Sumkina, O.V., & Kutsenko, L.B. (2019). Rak v Ukraini, 2017-2018. Zakhvoriuvanist, smertnist, pokaznyky diialnosti onkolohichnoi sluzhby [Cancer in Ukraine, 2017-2018. Morbidity, mortality, indicators of oncology service activity]. Biuleten Natsionalnoho kantser-reiestru Ukrainy – Bulletin of the National Cancer Register of Ukraine, 20, 100 [in Ukrainian].
Witjes, J.A., Bruins, M., Cathomas, R., Compérat, E., Cowan, N.C., Gakis, G. …, & Veskimäe, E. (2019). Muscle-invasive and Metastatic Bladder Cancer. EAU Guidelines. Edn. presented at the EAU Annual Congress Barcelona. The Netherlands, Arnhem: EAU Guidelines Office.
Sukocheva, O.A., Li, B., Due, S.L., Hussey, D.J., & Watson, D.I. (2015). Androgens and esophageal cancer: What do we know? World J. Gastroenterol., 21, 6146-6156.
Scosyrev, E., Noyes, K., Feng, C., & Messing, E. (2009). Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer, 115, 68-74. DOI: https://doi.org/10.1002/cncr.23986
Donsky, H., Coyle, S., Scosyrev, E., & Messing, E.M. (2014). Sex differences in incidence and mortality of bladder and kidney cancers: national estimates from 49 countries. Urol. Oncol., 32 (1), 40.e23-31. DOI: https://doi.org/10.1016/j.urolonc.2013.04.010
Dietrich, K., Demidenko, E., Schned, A., Zens, M.S., Heaney, J., & Karagas, M.R. (2011). Parity, early menopause and the incidence of bladder cancer in women: a case-control study and meta-analysis. Eur. J. Cancer, 47, 592-599. DOI: https://doi.org/10.1016/j.ejca.2010.10.007
Stenzl, A. (2010). Words of wisdom. Re: sex and racial differences in bladder cancer presentation and mortality in the US. Eur. Urol., 57, 729.
Edge, S.B., Byrd, D.R., Compton, C.C., Fritz, A.G., Greene, F., & Trotti, A. (Eds.) (2010). AJCC cancer staging manual (7th ed). New York, NY: Springer.
Shariat, S.F., Sfakianos, J.P., Droller, M.J., Karakiewicz, P.I., Meryn, S., & Bochner, B.H. (2010). The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int., 105, 300-308. DOI: https://doi.org/10.1111/j.1464-410X.2009.09076.x
Mungan, N.A., Kiemeney, L.A., & van Dijck, J.A. (2000). Gender differences in stage distribution of bladder cancer. Urology, 55, 368-371. DOI: https://doi.org/10.1016/S0090-4295(99)00481-1
Scosyrev, E., Trivedi, D., & Messing, E. (2010). Female bladder cancer: incidence, treatment, and outcome. Curr. Opin. Urol., 20, 404-408. DOI: https://doi.org/10.1097/MOU.0b013e32833c7a9b
Mallin, K., David, K.A., Carroll, P.R., Milowsky, M.I., & Nanus, D.M. (2011). Transitional cell carcinoma of the bladder: racial and gender disparities in survival (1993 to 2002), stage and grade (1993 to 2007). J. Urol., 185, 1631-1636. DOI: https://doi.org/10.1016/j.juro.2010.12.049
Kluth, L.A., Rieken, M., Xylinas, E., Kent, M., Rink, M., Rouprêt, M., …, & Shariat, S.F. (2014). Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of more than 8000 patients. Eur. Urol., 66, 913-919. DOI: https://doi.org/10.1016/j.eururo.2013.11.040
Mitra, A.P., Skinner, E.C., Schuckman, A.K., Quinn, D.I., Dorff, T.B., & Daneshmand, S. (2014). Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. Urol. Oncol., 32, 52.e1-9. DOI: https://doi.org/10.1016/j.urology.2014.05.080
Messer, J.C., Shariat, S.F., Dinney, C.P., Novara, G., Fradet, Y., Kassouf, W. ..., & Svatek, R.S. (2014). Female gender is associated with a worse survival after radical cystectomy for urothelial carcinoma of the bladder: a competing risk analysis. Urology, 83, 863-867. DOI: https://doi.org/10.1016/j.urology.2013.10.060
Fajkovic, H., Halpern, J.A., Cha, E.K., Bahadori, A., Chromecki, T.F., Karakiewicz, P.I., …, & Shariat, S.F. (2011). Impact of gender on bladder cancer incidence, staging, and prognosis. World J. Urol., 29, 457-463. DOI: https://doi.org/10.1007/s00345-011-0709-9
Soave, A., Dahlem, R., Hansen, J., Weisbach, L., Minner, S., & Engel, O., …, & Rink, M. (2015). Gender-specific outcomes of bladder cancer patients: a stage-specific analysis in a contemporary, homogenous radical cystectomy cohort. Eur. J. Surg. Oncol., 41, 368-377. DOI: https://doi.org/10.1016/j.ejso.2014.03.003
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., & Thun, M.J. (2008). Cancer statistics, 2008. CA Cancer J. Clin., 58, 71-96. DOI: https://doi.org/10.3322/CA.2007.0010
Siegel, R.L., Miller, K.D., & Jemal, A. (2019). Cancer statistics, 2019. CA Cancer J. Clin., 69, 7-34. DOI: https://doi.org/10.3322/caac.21551
Shariat, S.F., Karakiewicz, P.I., Palapattu, G.S., Lotan, Y., Rogers, C.G., Amiel, G.E., …, & Lerner, S.P. (2006). Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J. Urol., 176, 2414-2422. DOI: https://doi.org/10.1016/j.juro.2006.08.004
Garg, T., Pinheiro, L.C., Atoria, C.L., Donat, S.M., Weissman, J.S., Herr, H.W., & Elkin, E.B. (2014). Gender disparities in hematuria evaluation and bladder cancer diagnosis: a population based analysis. J. Urol., 192, 1072-1077. DOI: https://doi.org/10.1016/j.juro.2014.04.101
Hollenbeck, B.K., Dunn, R.L., Ye, Z., Hollingsworth, J.M., Skolarus, T.A., Kim, S.P., …, & Miller, D.C. (2010). Delays in diagnosis and bladder cancer mortality. Cancer, 116, 5235-5242. DOI: https://doi.org/10.1002/cncr.25310
Kluth, L.A., Fajkovic, H., Xylinas, E., Crivelli, J.J., Passoni, N., Rouprêt, M., …, & Gontero, P. (2013). Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder. World J. Urol., 31, 1029-1036. DOI: https://doi.org/10.1007/s00345-012-0996-9
Krimphove, M.J., Szymaniak, J., Marchese, M., Tully, K.H., D’Andrea, D., Mossanen, M., …, & Trinh, Q.-D. (2019). Sex-specific differences in the quality of treatment of muscle-invasive bladder cancer do not explain the overall survival discrepancy. Eur. Urol. Focus. pii: S2405-4569(19)30156-7.
Bilski, K., Zapała, Ł., Skrzypczyk, M.A., Oszczudłowski, M., & Dobruch, J. (2019). Review on gender differences in non-muscle invasive bladder cancer. Transl Androl. Urol., 8, 12-20. DOI: https://doi.org/10.21037/tau.2018.11.06
Afshar, N., English, D.R., Thursfield, V., Mitchell, P.L., Te Marvelde, L., Farrugia, H., …, & Milne, R.L. (2018). Differences in cancer survival by sex: a population-based study using cancer registry data. Cancer Causes Control, 29, 1059-1069. DOI: https://doi.org/10.1007/s10552-018-1079-z
Seo, M., & Langabeer Ii, J.R. (2018). Demographic and Survivorship Disparities in Non-muscle-invasive Bladder Cancer in the United States. J. Prev. Med. Public Health, 51, 242-247. DOI: https://doi.org/10.3961/jpmph.18.092
Uhlig, A., Seif Amir Hosseini, A., Simon, J., Lotz, J., Trojan, L., Schmid, M., & Uhlig, J. (2018). Gender specific differences in disease-free, cancer specific and overall survival after radical cystectomy for bladder cancer: A systematic review and meta-analysis. J. Urol., 200, 48-60. DOI: https://doi.org/10.1016/j.juro.2017.11.150
Wang, S.C., Sung, W.W., Kao, Y.L., Hsieh, T.Y., Chen, W.J., Chen, S.L., & Chang, H.R. (2017). The gender difference and mortality-to-incidence ratio relate to health care disparities in bladder cancer: National estimates from 33 countries. Sci. Rep., 7, 4360.
Andreassen, B.K., Grimsrud, T.K., & Haug, E.S. (2018). Bladder cancer survival: Women better off in the long run. Eur. J. Cancer, 95, 52-58. DOI: https://doi.org/10.1016/j.ejca.2018.03.001
Patafio, F.M., Robert Siemens, D., Wei, X., & Booth, C.M. (2015). Is there a gender effect in bladder cancer? A population-based study of practice and outcomes. Can. Urol. Assoc. J., 9, 269-274. DOI: https://doi.org/10.5489/cuaj.2927
Heberling, U., Koch, R,, Hübler, M., Baretton, G.B., Hakenberg, O.W., Wirth, M.P., & Froehner, M. (2018). Gender and mortality after radical cystectomy: Competing risk analysis. Urol. Int., 101, 293-299. DOI: https://doi.org/10.1159/000487445
Pichler, R., Fritz, J., Heidegger, I., Oberaigner, W., Horninger, W., & Hochleitner, M. (2017). Gender-related outcome in bladder cancer patients undergoing radical cystectomy. J. Cancer, 8, 3567-3574. DOI: https://doi.org/10.7150/jca.21130
Zhuang, Y.H., Bläuer, M., Tammela, T., & Tuohimaa, P. (1997). Immunodetection of androgen receptor in human urinary bladder cancer. Histopathology, 30, 556-562. DOI: https://doi.org/10.1046/j.1365-2559.1997.5610801.x
Boorjian, S., Ugras, S., Mongan, N.P., Gudas, L.J., You, X., Tickoo, S.K., & Scherr, D.S. (2004). Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology, 64, 383-388. DOI: https://doi.org/10.1016/j.urology.2004.03.025
Saez, S., & Martin, P.M. (1981). Evidence of estrogen receptors in the trigone area of human urinary bladder. J. Steroid Biochem., 15, 317-320. DOI: https://doi.org/10.1016/0022-4731(81)90291-0
Shen, S.S., Smith, C.L., Hsieh, J.T., Yu, J., Kim, I.Y., Jian, W., …, & Lerner, S.P. (2006). Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer, 106, 2610-2616. DOI: https://doi.org/10.1002/cncr.21945
Erben, P., Sikic, D., Wirtz, R.M., Martini, T., Weis, C.A., Breyer, J., …, & Bolenz, C. (2019). Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder. Virchows Arch., 474, 209-217. DOI: https://doi.org/10.1007/s00428-018-2496-9
Godoy, G., Gakis, G., Smith, C.L., & Fahmy, O. (2016). Effects of androgen and estrogen receptor signaling pathways on bladder cancer initiation and progression. Bladder Cancer, 2, 127-137. DOI: https://doi.org/10.3233/BLC-160052
Ide, H., & Miyamoto, H. (2015). Steroid hormone receptor signals as prognosticators for urothelial tumor. Dis. Markers, 840640. DOI: https://doi.org/10.1155/2015/840640
Huang, W., Chen, Y., Liu, Y., Zhang, Q., Yu, Z., Mou, L., …, & Gui, Y. (2015). Roles of ERβ and GPR30 in proliferative response of human bladder cancer cell to estrogen. Biomed. Res. Int., 251780.
Tan, W., Boorjian, S., Advani, P., Farmer, S., Lohse, C., Cheville, J., …, & Leibovich, B. (2015). The estrogen pathway: Estrogen receptor-α, progesterone receptor, and estrogen receptor-β expression in radical cystectomy urothelial cell carcinoma specimens. Clin. Genitourin Cancer, 13, 476-484. DOI: https://doi.org/10.1016/j.clgc.2015.04.001
McGrath, M., Michaud, D.S., & De Vivo, I. (2006). Hormonal and reproductive factors and the risk of bladder cancer in women. Am J. Epidemiol., 163, 236-244. DOI: https://doi.org/10.1093/aje/kwj028
Dobruch, J., Daneshmand, S., Fisch, M., Lotan, Y., Noon, A.P., Resnick, M.J., …, & Boorjian, S.A. (2016). Gender and bladder cancer: A collaborative review of etiology, biology, and outcomes. Eur. Urol., 69, 300-310. DOI: https://doi.org/10.1016/j.eururo.2015.08.037
Gakis, G., & Stenzl, A. (2013). Gender-specific differences in muscle-invasive bladder cancer: the concept of sex steroid sensitivity. World J. Urol., 31, 1059-1064. DOI: https://doi.org/10.1007/s00345-013-1037-z
Chen, F., Langenstroer, P., Zhang, G., Iwamoto, Y., & See, W. (2003). Androgen dependent regulation of bacillus Calmette-Guerin induced interleukin-6 expression in human transitional carcinoma cell lines. J. Urol., 170, 2009-2013. DOI: https://doi.org/10.1097/01.ju.0000092238.15685.10
Okajima, E., Hiramatsu, T., Iriya, K., Ijuin, M., Matsushima, S., & Yamada, K. (1975). Effects of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Urol. Res., 3, 73-79. DOI: https://doi.org/10.1007/BF00256185
Miyamoto, H., Yang, Z., Chen, Y.T., Ishiguro, H., Uemura, H., Kubota, Y., …, & Chang, C. (2007). Promotion of bladder cancer development and progression by androgen receptor signals. J. Natl. Cancer Inst., 99, 558-568. DOI: https://doi.org/10.1093/jnci/djk113
Boorman, G.A. (1977). Animal model of human disease: carcinoma of the ureter and urinary bladder. Am. J. Pathol., 88, 251-254.
Miyamoto, H., Yao, J.L., Chaux, A., Zheng, Y., Hsu, I., Izumi, K., …, & Yeh, S. (2012). Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int., 109, 1716-1726. DOI: https://doi.org/10.1111/j.1464-410X.2011.10706.x
Imada, S., Akaza, H., Ami, Y., Koiso, K., Ideyama, Y., & Takenaka, T. (1997). Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats. Eur. Urol., 31, 360-364. DOI: https://doi.org/10.1159/000474484
Hoffman, K.L., Lerner, S.P., & Smith, C.L. (2013). Raloxifene inhibits growth of RT4 urothelial carcinoma cells via estrogen receptor-dependent induction of apoptosis and inhibition of proliferation. Horm. Cancer, 4, 24-35. DOI: https://doi.org/10.1007/s12672-012-0123-9
Boorjian, S.A., Heemers, H.V., Frank, I., Farmer, S.A., Schmidt, L.J., Sebo, T.J., & Tindall, D.J. (2009). Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder. Endocr. Relat. Cancer, 16, 123-137. DOI: https://doi.org/10.1677/ERC-08-0124
Lombard, A.P., & Mudryj, M. (2015). The emerging role of the androgen receptor in bladder cancer. Endocr. Relat. Cancer, 22, R265-77. DOI: https://doi.org/10.1530/ERC-15-0209
Ren, B., Li, W., Yang, Y., & Wu, S. (2014). The impact of cyclin D1 overexpression on the prognosis of bladder cancer: a meta-analysis. World J. Surg. Oncol., 12, 55. DOI: https://doi.org/10.1186/1477-7819-12-55
Li, W., Liu, J., Zou, D., Cai, X., Wang, J., Wang, J., …, & Xu, Y. (2017). Exploration of bladder cancer molecular mechanisms based on miRNA-mRNA regulatory network. Oncol. Rep., 37, 1461-1468. DOI: https://doi.org/10.3892/or.2017.5433
Zhao, J., Xu, W., Zhang, Z., Song, R., Zeng, S., Sun, Y., & Xu, C. (2015). Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis. Int. Urol. Nephrol., 47, 87-94. DOI: https://doi.org/10.1007/s11255-014-0866-z
Johnson, A.M., O'Connell, M.J., Miyamoto, H., Huang, J., Yao, J.L., Messing, E.M., & Reeder, J.E. (2008). Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1. BMC Urol., 8, 7. DOI: https://doi.org/10.1186/1471-2490-8-7
Zhang, Y. (2013). Understanding the gender disparity in bladder cancer risk: the impact of sex hormones and liver on bladder susceptibility to carcinogens. J Environ Sci Health C Environ Carcinog. Ecotoxicol. Rev., 31, 287-304. DOI: https://doi.org/10.1080/10590501.2013.844755
Izumi, K., Zheng, Y., & Hsu, J.W. (2013). Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis. Mol. Carcinog, 52, 94-102. DOI: https://doi.org/10.1002/mc.21833
Wirtz, R.M., Fritz, V., Stöhr, R., & Hartmann, A. (2016). Molecular classification of bladder cancer. Possible similarities to breast cancer. Pathologe, 37, 52-60. DOI: https://doi.org/10.1007/s00292-015-0134-8
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