Molecular characteristics, treatment patterns, and survival outcomes in biliary tract cancers: A retrospective analysis from a high-prevalence region.

Abstract

4109 Background: Biliary tract cancers (BTC) present significant challenges in management due to their aggressive nature and often late-stage presentation. We present demographic trends, molecular characteristics, treatment patterns, and survival outcomes. Methods: This retrospective study included patients diagnosed with BTC between March 2018 and September 2024. Survival analysis was done using the Kaplan-Meier analysis. Results: Total of 743 patients were diagnosed with BTC, median age of the cohort was 61 years (IQR 52-69); with F: M ratio being 1.15:1. Distribution according to the stage at presentation was: stage I (n=15, 2%), stage II (n=49,6.6%), Stage III (n=160, 21.5%) and stage IV (n=509, 68.5%). History of gallstones was reported in 183 patients (24.6%). Out of the total cohort, 436 patients (58.7%) had gallbladder cancers (GBCs) while 307 patients (41.3%) had cholangiocarcinoma (CCA), where n=202 (65.8%) were intrahepatic, n=22 (7.2%) were perihilar and n=33 (10.7%) were distal bile duct. Predominant histologic patterns among GBCs were: adenocarcinomas n=331 (75.9%), small cell carcinomas n=13(3%) adenosquamous n=11(2.5%), and others n=81(18.5%). Molecular testing was done in 132 patients (17.8%), out of which 11/132 (8.3%) had HER2 alteration, wherein overexpression was seen in n=3,while amplification was seen in n=8; TP53 mutation was seen in 21/132 (16%), while others alterations were MSI-high (n=2), TMB-high (≥10 mut/Mb) (n=3), PDL1 positive (n=24), FGFR(n=3), IDH (n=2), BRCA2 (n=2). Treatment and survival outcomes were available for 492 patients, surgery was done in 177 patients (35.9%), systemic therapy (adjuvant/palliative) was done in 431 (87.6%) patients while targeted or immunotherapy was used in 99 patients (20.1%). Median Overall survival (mOS) of the cohort was 16.1 months (13.6-18.6) with a median follow-up duration of 28.2 months (23.2 – 33.2). mOS for GBC was 10.8(8.2-13.3) months and CCA was11.6(9.3-14.0) months. mOS for Metastatic BTC was 9.6 months while for Non-metastatic it was 20.4 months(p<0.001). The median mOS for patients with HER2 mutations, TP53 mutations, and PD-L1 positivity were 23.8 months, 16.6 months, and 10.0 months, respectively (p = 0.165). Conclusions: In high-prevalence countries like India, biliary tract cancer (BTC) management is challenged by advanced stage presentation, limited molecular testing and resource constraints. Efforts to enhance molecular testing and treatment access are critical for practicing precision oncology and improving treatment outcomes.