Preoperative Alkaline Phosphatase-adjusted CA19-9 As a Superior Prognosticator for Extrahepatic Biliary Tract Cancer With Jaundice

Overview

Journal Cancer Diagn Progn

Specialty Oncology

Date 2022 Sep 5

PMID 36060020

Authors

Shinichi Ikuta

Tsukasa Aihara

Takayoshi Nakajima

Meidai Kasai

Naoki Yamanaka

Affiliations

Soon will be listed here.

Abstract

Background/aim: The major limitation of carbohydrate antigen (CA)19-9 as a tumor marker is the high incidence of false-positive results during cholestasis. We evaluated preoperative CA19-9 and its adjusted values [ratios of CA19-9 to total-bilirubin (TB), direct-bilirubin (DB), and alkaline phosphatase (ALP)] to investigate the most suitable prognostic parameter in extrahepatic biliary tract cancer (eBTC) patients with or without jaundice.

Patients And Methods: eBTC patients (n=140) who underwent resection were divided based on the absence (TB <2.0 mg/dl, n=90) or presence (TB ≥2.0 mg/dl, n=50) of preoperative jaundice. Within each group, the associations with overall survival (OS) were assessed for CA19-9, CA19-9/TB, CA19-9/DB and CA19-9/ALP ratios using Cox regression, receiver operating characteristic (ROC) analyses, and area under the curve (AUC) estimates.

Results: In univariate analysis in the group without jaundice, both high CA19-9 and high CA19-9/TB ratio were associated with poor OS, whereas other parameters were not. ROC-AUC for OS prediction was greater in CA19-9 than in the CA19-9/TB ratio, and CA19-9 was identified as an independent prognosticator in multivariate analysis. In the group with jaundice, CA19-9 was not significant; however, CA19-9/TB, CA19-9/DB, and CA19-9/ALP ratios were all associated with poor OS. In ROC-AUC analysis, CA19-9/ALP ratio showed the highest predictive value; furthermore, it was an independent prognosticator in multivariate analysis.

Conclusion: Adjustment of the CA19-9 value was less useful as a predictor in the absence of jaundice. On the other hand, the CA19-9/ALP ratio showed superior prognostic value in jaundiced patients with eBTC.

References

Bridgewater J, Goodman K, Kalyan A, Mulcahy M . Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling. Am Soc Clin Oncol Educ Book. 2016; 35:e194-203. DOI: 10.1200/EDBK_160831. View

Li J, Chen Q, Jin B, Shi Y, Wu X, Xu H . Preoperative Bilirubin-Adjusted Carbohydrate Antigen 19-9 as a Prognostic Factor for Extrahepatic Cholangiocarcinoma Patients at a Single Center. Cancer Manag Res. 2020; 12:411-417. PMC: 6980863. DOI: 10.2147/CMAR.S229329. View

Kang C, Kim J, Choi G, Kim K, Choi J, Lee W . The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007; 140(1):31-5. DOI: 10.1016/j.jss.2006.10.007. View

Kim H, Kim M, Myung S, Lim B, Park E, Yoo K . A new strategy for the application of CA19-9 in the differentiation of pancreaticobiliary cancer: analysis using a receiver operating characteristic curve. Am J Gastroenterol. 1999; 94(7):1941-6. DOI: 10.1111/j.1572-0241.1999.01234.x. View

Limdi J, HYDE G . Evaluation of abnormal liver function tests. Postgrad Med J. 2003; 79(932):307-12. PMC: 1742736. DOI: 10.1136/pmj.79.932.307. View

Lin M, Huang J, Yu H . Elevated serum level of carbohydrate antigen 19-9 in benign biliary stricture diseases can reduce its value as a tumor marker. Int J Clin Exp Med. 2014; 7(3):744-50. PMC: 3992417. View

Wiltberger G, Krenzien F, Benzing C, Atanasov G, Klein F, Hau H . Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma. Ann Surg Oncol. 2015; 23(4):1320-6. DOI: 10.1245/s10434-015-4999-9. View

Regmi P, Paudyal A, Paudyal P, Hu H, Liu F, Ma W . Prognostic significance of tumor budding in biliary tract cancer. Eur J Surg Oncol. 2021; 48(1):160-168. DOI: 10.1016/j.ejso.2021.08.008. View

Kawamata H, Yamashita K, Nakamura K, Katagiri H, Ishii K, Takahashi Y . Perineural invasion and preoperative serum CA19-9 as predictors of survival in biliary tract cancer. Anticancer Res. 2013; 33(2):583-94. View

10.

Levitt M, Hapak S, Levitt D . Alkaline Phosphatase Pathophysiology with Emphasis on the Seldom-Discussed Role of Defective Elimination in Unexplained Elevations of Serum ALP - A Case Report and Literature Review. Clin Exp Gastroenterol. 2022; 15:41-49. PMC: 8934114. DOI: 10.2147/CEG.S345531. View

11.

Schlieman M, Ho H, Bold R . Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003; 138(9):951-5; discussion 955-6. DOI: 10.1001/archsurg.138.9.951. View

12.

Beetz O, Klein M, Schrem H, Gwiasda J, Vondran F, Oldhafer F . Relevant prognostic factors influencing outcome of patients after surgical resection of distal cholangiocarcinoma. BMC Surg. 2018; 18(1):56. PMC: 6090737. DOI: 10.1186/s12893-018-0384-5. View

13.

Bolm L, Petrova E, Weitz J, Ruckert F, Wittel U, Makowiec F . Prognostic relevance of preoperative bilirubin-adjusted serum carbohydrate antigen 19-9 in a multicenter subset analysis of 179 patients with distal cholangiocarcinoma. HPB (Oxford). 2019; 21(11):1513-1519. DOI: 10.1016/j.hpb.2019.03.363. View

14.

Marrelli D, Caruso S, Pedrazzani C, Neri A, Fernandes E, Marini M . CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg. 2009; 198(3):333-9. DOI: 10.1016/j.amjsurg.2008.12.031. View

15.

Kodama T, Satoh H, Ishikawa H, Ohtsuka M . Serum levels of CA19-9 in patients with nonmalignant respiratory diseases. J Clin Lab Anal. 2007; 21(2):103-6. PMC: 6648978. DOI: 10.1002/jcla.20136. View

16.

Westwood A . The analysis of bilirubin in serum. Ann Clin Biochem. 1991; 28 ( Pt 2):119-30. DOI: 10.1177/000456329102800202. View

17.

Kondo N, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Sasaki H . Elevated perioperative serum CA 19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma. J Surg Oncol. 2014; 110(4):422-9. DOI: 10.1002/jso.23666. View

18.

Dumitra S, Jamal M, Aboukhalil J, Doi S, Chaudhury P, Hassanain M . Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score. HPB (Oxford). 2013; 15(12):1002-9. PMC: 3843620. DOI: 10.1111/hpb.12085. View

19.

Schemper M, Smith T . A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996; 17(4):343-6. DOI: 10.1016/0197-2456(96)00075-x. View

20.

Ong S, Sachdeva A, Garcea G, Gravante G, Metcalfe M, Lloyd D . Elevation of carbohydrate antigen 19.9 in benign hepatobiliary conditions and its correlation with serum bilirubin concentration. Dig Dis Sci. 2008; 53(12):3213-7. DOI: 10.1007/s10620-008-0289-8. View