Raised carbohydrate antigen 19-9 levels detect recurrences and impacts overall and disease-free survival in radically resected gallbladder cancer: A simple surveillance marker?

There are no established markers which can be used for surveillance after curative resection in gallbladder carcinoma (GBC). Though carbohydrate antigen 19-9 (CA 19-9) has low specificity as a diagnostic marker, its role as a surveillance marker has not been explored. The aim of this study is to evaluate the predictive ability of CA 19-9 as a surveillance marker to detect recurrences on follow-up. A retrospective analysis of a prospectively maintained database of radically resected GBC who were either on observation or completed adjuvant therapy (chemotherapy or chemoradiation) were followed up 3 monthly with CA 19-9 and ultrasound (US) abdomen for the first 2 years and 6 monthly CA 19-9 and US for further 3 years. Patients with raised CA 19-9 and a recurrent lesion on US abdomen were confirmed with contrast-enhanced computed tomography (CECT) abdomen and fine-needle aspiration cytology (FNAC) of recurrent lesion to establish the diagnosis of recurrence. The performance of CA 19-9 levels (20 and more units/mL) for prediction of recurrence and its impact on survival was estimated. Out of sixty patients on follow-up, 40% recurred: loco-regional (16.7%) and distant metastases (23.4%). The sensitivity, specificity, positive predictive value, and negative predictive value of CA 19-9 in detecting recurrence were 79.1%, 97.2%, 95%, and 87.5%, respectively. The median disease-free survival was 56 months versus 15 months (P = 0.008, hazard ratio [HR]: 7.4 [1.3-40]) and the median overall survival was not reached versus 20 months (P = 0.000, HR: 10.7 [confidence interval 4.2-27.3]) for CA 19-9 levels less than and more than 20 ng/mL. Based on the high positive and negative predictive value in our dataset, CA 19-9 can be used as a surveillance biomarker for follow-up of radically resected GBC. Raised levels of >20 ng/mL should be correlated with imaging findings and any suspicious lesion should be confirmed for recurrence by FNAC and CECT abdomen. Levels >20 ng/mL should be taken as a threshold for suspecting recurrence.