Evaluating Surrogate Endpoints in Advanced Biliary Tract Cancer: Progression-Free Survival Outperforms Response Rates as a Predictor of Overall Survival

Background and Disease Burden

Biliary tract cancer (BTC) encompasses a heterogeneous group of malignancies arising from the biliary epithelium, including intrahepatic and extrahepatic cholangiocarcinomas as well as gallbladder cancer. Despite relatively low incidence compared to other gastrointestinal cancers, BTC carries a poor prognosis, with most patients presenting at an advanced stage where curative treatment options are limited. Median overall survival (OS) in advanced BTC remains dismal despite systemic therapies, highlighting an urgent need for effective treatments.

In clinical oncology research, overall survival has historically been considered the gold standard endpoint for evaluating therapeutic efficacy. However, OS measurement requires long follow-up durations, is influenced by post-progression therapies, and demands large sample sizes and significant resources. To expedite drug development, surrogate endpoints such as progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) have increasingly been used in BTC trials. Surrogate endpoints can shorten trial duration and reduce costs but must reliably predict OS benefits to be clinically meaningful.