Drug Sensitivity of Circulating Tumor Cells as a Game-Changer in Subsequent-Line Therapy for Biliary Tract Carcinoma

Biliary tract carcinoma (BTC) is an aggressive cancer with a poor prognosis, and chemotherapy’s effectiveness is limited, especially after first-line therapy failure. Circulating tumor cells (CTCs) offer a platform for in vitro drug-sensitivity testing to optimize subsequent-line chemotherapy, but the clinical efficacy and prognostic value remains well-established. In this study, we retrospectively analyzed 85 advanced BTC patients, with 25 receiving CTC-based drug-sensitivity-guided chemotherapy (CSBT), 15 receiving FOLFOX, and 45 receiving empirical therapy. CTCs were enriched and tested for drug sensitivity using a glucose uptake assay. Therapeutic efficacy, including patient response, progression-free survival (PFS), overall survival (OS), and toxicity profiles, was evaluated. The results indicated that the objective response rate (ORR) was 16% in CSBT, 6.7% in FOLFOX, and 4.4% in the empirical group. The disease control rate (DCR) was significantly higher in CSBT group (56%) compared to the FOLFOX (20%) and empirical therapy (22.2%; p  < 0.05) groups. Median PFS was significantly prolonged in the CSBT group (5.4 months) versus the FOLFOX (1.9 months) and empirical therapy (2.7 months; p  < 0.05) groups. Median OS was extended in the CSBT group (12 months), with a significant improvement in OS during the first year of treatment ( p  < 0.05). Toxicity profiles were similar across all groups. In conclusion, this study for the first time proved that CTC-based drug-sensitivity testing offers a potential approach to guide chemotherapy for advanced BTC. Furthermore, this approach does not increase the risk of severe adverse events, highlighting its potential as a safe and effective strategy for improving patient prognosis in advanced BTC.