Role of serum CA 19-9 as a tumor marker in TCC bladder

Rajeev T. P., Nabajeet Das, S. J. Baruah, S. K. Barua, P. K. Bagchi, D. Sarma, M. Phukan


Background: There is a dearth of reliable blood and urine markers for transitional cell carcinoma of urinary bladder. CA 19-9 is a well-known marker for gastrointestinal malignancies and is being investigated for other malignancies including carcinoma bladder. In this prospective study, we evaluated the role of serum CA 19-9 as a tumor marker and correlated its level with tumor grade and stage.

Methods: One hundred and fifteen patients with transitional cell carcinoma of urinary bladder and 69 healthy volunteers, as controls were included in the study. Preoperative blood sample was analysed for level of CA 19-9 using ELISA kit (normal - 0 U/ml to 37U/ml) and were correlated with grade and TNM stage of tumor.

Results: The range of the control group is 2-38U/ml (mean: 17.67±9.68U/ml); TCC group is 1-94U/ml (mean: 37.12±31.52U/ml) (p=0.304). When CA 19-9 level >37IU/ml was taken as cut-off for a positive test, sensitivity of detecting T3 disease, T4 disease, MIBC, presence of node and high grade tumour were 80%, 75%, 70.3%, 78% and 57.8% respectively. However, there was a statistically significant increase in levels of CA19-9 in relation to higher grade (<0.001), presence of muscle invasion (<0.001), T stage (<0.001) and N stage (<0.001).

Conclusions: Serum CA19-9 is almost invariably raised in patients with high grade and invasive disease. Thus, it has a place as a prognostic marker rather than as a diagnostic tool due to its low sensitivity for TCC bladder.


High grade bladder cancer, Muscle invasive bladder cancer, Prognostic tumour marker, Transitional cell carcinoma, Serum tumor marker, Serum CA 19-9

Full Text:



Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v10. Cancer incidence and mortality worldwide: IARC Cancer Base. 2013.

Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009;27(3):289-93.

Takiar R, Nadayil D, Nandakumar A. Projections of number of cancer cases in India (2010-2020) by cancer groups. Asian Pac J Cancer Prev. 2010;11(4):1045-9.

Ro JY, Staerkel GA, Ayala AG. Cytologic and histologic features of superficial bladder cancer. The Urologic Clinics North America. 1992;19(3):435-53.

Fitzpatrick JM, West AB, Butler MR, Lane V, O’Flynn JD. Superficial bladder tumors (stage pTa, grades 1 and 2): the importance of recurrence pattern following initial resection. J Urol. 1986 May;135(5):920-2.

Greene LF, Hanash KA, Farrow GM. Benign papilloma or papillary carcinoma of the bladder? J Urol. 1973;(110):205-7.

Tut VM, Hildreth AJ, Kumar M, Mellon JK. Does voided urine cytology have biological significance? British J Urol. 1998;82(5):655-9.

Lutzeyer W, Rubben H, Dahm H. Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J Urol. 1988;127:250-2.

HB G. New methods for detection of bladder cancer. Semin Urol Oncol. 1998;16:17-22.

Shelfo SW SM. The role of nuclear matrix protein 22 in the detection of persistent or recurrent transitional cell cancer of the bladder. World J Urol. 1997;15:107-11.

Papanicolaou GN, Marshall VF. Urine sediment smears as a diagnostic procedure in cancer of urinary tract. Science. 1945;101:519-20.

Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5:957-71.

Poulakis V, Witzsch U, De Vries R, Altmannsberger HM, Manyak MJ, et al. A comparison of urinary nuclear matrix protein-22 and bladder tumor antigen tests with voided urinary cytology in detecting and following bladder cancer: The prognostic value of false-positive results. BJU Int. 2001;88:692-701.

Ewing R, Tate GM, Hetherington JW. Urinary fibrin/fibrinogen degradation products in transitional cell carcinoma of the bladder. Br J Urol. 1987;59:53-8.

Perkins GL, Slater ED, Sanders GK, Prichard JG. Serum tumor markers. American family physician. 2003;68(6):1075-88.

MJ. The discovery, biology, and drug development of sialyl Lea and sialyl Lex. Archives of biochemistry and biophysics. 2004;426(2):122-31.

Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. EJSO. 2007;33(3):266-70.

Boeck S, Stieber P, Holdenrieder S, Wilkowski R, Heinemann V. Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer. Oncology. 2006;70(4):255-64.

Inai H, Shimazui T, Yamamoto T, Yamauchi A, Uchida K, Takeshima H, et al. A case of transitional cell carcinoma of the urinary bladder with high serum level of CEA and CA19-9. Hinyokika kiyo. Acta urologica Japonica. 2001;47(8):583-6.

Kato S, Yasuda M, Nakano M, Ehara H, Ishihara T, Deguchi T, et al. Superficial urothelial carcinoma of ureter with elevated serum CA19-9 and CEA. Hinyokika kiyo. Acta Urologica Japonica. 2004;50(2):99-102.

Hegele A, Mecklenburg V, Varga Z, Olbert P, Hofmann R, Barth P. CA19. 9 and CEA in transitional cell carcinoma of the bladder: serological and immunohistochemical findings. Anticancer Res. 2010;30(12):5195-200.

Pall M, Iqbal J, Singh SK, Rana SV. CA 19-9 as a serum marker in urothelial carcinoma. Urology Annals. 2012;4(2):98.

Margel D, Tal R, Neuman A, Konichezky M, Sella A, Baniel J. Prediction of extravesical disease by preoperative serum markers in patients with clinically organ confined invasive bladder cancer. Journal Urol. 2006;175(4):1253-7.

Pectasides D, Bafaloucos D, Antoniou F, Gogou L, Economides N, Varthalitis J, et al. TPA, TATI, CEA, AFP, β-HCG, PSA, SCC, and CA 19-9 for monitoring transitional cell carcinoma of the bladder. Am J Clin Oncol. 1996;19(3):271-7.

Sugaya Y, Ochi M, Hashimoto S, Muraki J, Morita T, Kobayashi Y, et al. A case of transitional cell carcinoma of renal pelvis with extremely high serum levels of CA19-9 and CEA. Hinyokika kiyo. Acta Urologica Japonica. 1997;43(7):495-9.

Yamamoto H, Ueda Y, Maruyama T, Kondou N, Nojima M, Takiuchi H, et al. A case of CA19-9 producing transitional cell carcinoma of the ureter. Hinyokika kiyo. Acta Urol Japonica. 2003;49(9):543-5.

Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001;19(3):666-75.

Dalbagni G, Genega E, Hashibe MI, Zhang ZF, Russo P, Herr H. Cystectomy for bladder cancer: a contemporary series. J Urol. 2001;165(4):1111-6.

Otto T, Goepel M, Heider KH, Rübben H. Prognostic factors for bladder cancer. Urological Res. 1995;23(3):137-41.

Schrag D, Hsieh LJ, Rabbani F, Bach PB, Herr H, Begg CB. Adherence to surveillance among patients with superficial bladder cancer. J National Cancer Institute. 2003;95(8):588-97.

Jones JS. Non muscle invasive bladder cancer. In Alan J. Wein LRKAWPCA, editor. Campbell-Walsh urology. 11th ed. Philadelphia: Elsevier; 2016:2205-2223.

Lokeshwar VB, Habuchi T, Grossman HB, Murphy WM, Hautmann SH. Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers. Urology. 2005;66(6):35-63.

Vrooman OP, Witjes JA. Urinary markers in bladder cancer. European Urol. 2008;53(5):909-16.

Sashide K, Isobe H, Wakumoto Y, Hanazawa K, Fujita K, Fujime M. CA19-9 as a serum marker for poor prognosis in urothelial carcinoma. Urologia Internationalis. 2004;72(2):112-7.

Itzkowitz SH, Kim YS. New carbohydrate tumor markers. Gastroenterology. 1986;90(2):491-4.

Itzkowitz SH, Yuan M, Fukushi Y, Lee H, Shi Z, Zurawski V, et al. Immunohistochemical comparison of Lea, monosialosyl Lea (CA 19-9), and disialosyl Lea antigens in human colorectal and pancreatic tissues. Cancer research. 1988;48(13):3.

Kurokawa K, Kurihara J, Nakata S, Matsuo Y, Ebihara K, Kurihara H, et al. The clinical significance of carbohydrate antigen 19-9 (CA19-9) in transitional cell cancer of urinary tract. Nihon Hinyokika Gakkai zasshi. Japanese J Urol. 1993;84(6):1074-81.

Lynch CF, Cohen MB. Urinary system. Cancer. 1995;75(S1):316-29.