Different Tumour Marker Kinetics as Prognosticators in Patients with Adenocarcinoma of Gall Bladder Undergoing Chemotherapy: A Cohort Study

Abstract

Introduction: Gallbladder Cancer (GBC) is the most common malignancy of the biliary tract worldwide. Patients do not have specific symptoms, and therefore, GBC is usually diagnosed at an advanced stage. Carbohydrate Antigen (CA)-242, CA 19-9, and Cancer Antigen 125 (CA-125) have been found to be effective in the diagnosis and prognosis of GBC. Aim: To determine the significance of tumour markers as prognosticators in adenocarcinoma of GBC with chemotherapy. Materials and Methods: The present cohort study was conducted in the Department of Biochemistry, Murshidabad Medical College and Hospital, Baharampur, West Bengal, India, between December 2021 and November 2022. Thirty patients with pathologically confirmed adenocarcinoma of the gallbladder who were treated with gemcitabine-based chemotherapy were included in the study. Differences in serum CA-125 and CA 19-9 levels before and after chemotherapy (KINETICS) were measured along with haemoglobin, serum urea, creatinine, total bilirubin and Neutrophil-Lymphocyte Ratio (NLR). Receiver Operating Characteristic (ROC) curve analysis and Kaplan-Meier analyses of CA-125, CA 19-9, and combined changes were performed to assess survival rates and their statistical relevance as prognosticators in correlation with disease progression. Results: The mean±Standard Deviation (SD) age was 52.4±5.275 years. A total of 25 (83.3%) patients were females. The associations of CA 19-9 change with other baseline variables were analysed, and there were significant associations with baseline Carbohydrate Antigen (CA19-9) levels (p-value=0.003) and metastatic changes (p-value <0.001). Patients with decreased tumour markers had significantly better Progression-Free Survival (PFS) than patients with increased tumour markers. The pre- and post-chemotherapy CA 19-9 ratio had the highest area-under-the-curve values (AUC 0.910) for predicting 6-month PFS, whereas for predicting metastatic changes, the combined pre- and post-chemotherapy marker ratio had the highest AUC 0.842. In the multivariate analysis, CA 19-9 ≥100 U/mL at diagnosis (p-value <0.001) and NLRchange ≥1.0 (p-value=0.003) were independent prognosticators of PFS, with hazard ratios of 1.007 (p-value <0.001) and 15.4 (p-value=0.003), respectively. Conclusion: CA 19-9 kinetics proved to be a reliable prognosticator of metastatic changes in patients with adenocarcinoma of the gallbladder undergoing chemotherapy. The significant decline in tumour markers that were seen throughout the follow-up phase emphasises how important it is to use these markers as primary indicators of treatment response. To validate the present study findings, larger-scale studies involving a longer follow-up period and a greater number of patients are needed.

Keywords

• gallbladder cancer
• metastasis
• prognostic marker
• serum carbohydrate antigen