Introduction
Perihilar cholangiocarcinoma (pCCA) is a rare malignancy originating from the bile duct bifurcation which is often diagnosed in an advanced stage. Most patients require endoscopic or percutaneous biliary drainage, as they present themselves with jaundice and/or cholangitis. In most Western countries, only palliative chemotherapy (pCTx) is offered to these patients, positively impacting overall survival and quality of life. Unfortunately, median survival is still poor, with only 10.6 months in patients receiving pCTx, compared to a dismal 4.0 months in patients receiving best supportive care (1). For non-resected pCCA, there is much debate on the optimal technique of biliary drainage, which is often deemed necessary to initiate pCTx. This study aimed to investigate the impact of biliary drainage on pCTx initiation and survival in patients with non-resected pCCA.
Aims & Methods
Individual patient data from all Dutch patients diagnosed with non-resected pCCA between 2015 and 2020 were retrieved from the Netherlands Cancer Registry. Survival data was last updated on 1st of February 2024. Data was retrieved and de-identified by trained data clerks. The primary outcome was pCTx initiation. Secondary outcome was overall survival. For both the primary and secondary outcome, associations were investigated for several (biliary drainage) factors by multivariable competing risk regression analysis. Initial drainage procedure and initiation of pCTx were treated as time-varying covariates. Sensitivity analysis for pathologically proven pCCA was performed.
Results
A total of 1265 patients (median age of 74 years [IQR: 66-82 years]) were included, of whom 242 patients (19.1%) received pCTx after a median interval of 72 days [IQR 43-110 days] after initial presentation. Patients who underwent biliary drainage did not receive pCTx more often. If performed, drainage at a referral hospital (HR:0.65, 95%CI: 0.42-0.99), ≥3 drainage procedures performed (HR:0.53, 95%CI: 0.32-0.88), and drainage performed ≥14 days after presentation (HR:0.70, 95%CI: 0.49-0.99) were associated with no pCTx. Median overall survival for those who received pCTx and those who did not was 12.8 months [95%CI: 11.7-14.2] and 2.7 months [95%CI: 2.4-3.1]. Receiving of pCTx was associated with improved overall survival (HR:0.61, 95%CI: 0.51-0.73), but biliary drainage was not. If performed, biliary drainage by percutaneous trans-hepatic catheter placement compared to endoscopic plastic stenting (HR:1.27, 95%CI: 1.02-1.57) was associated with diminished survival, and drainage performed ≥14 days after presentation (HR: 0.76, 95% CI: 0.65-0.88) was associated with improved overall survival. Sensitivity analysis for pathologically confirmed pCCA showed similar results.
Conclusion
The need for biliary drainage did not affect the initiation of pCTx. When indicated, biliary drainage should be performed as quick as possible in an academic center to improve the rate of patients receiving pCTx.
References
- Izquierdo-Sanchez L, Lamarca A, La Casta A, Buettner S, Utpatel K, Klumpen HJ, et al. Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol. 2022;76(5):1109-21.
Disclosure
J. de Vos-Geelen has served as a consultant for Amgen, AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier (all outside the submitted work). RPV reports a research grant and consultancy fees from Boston Scientific, research grant from Prion medical, Consultancy fee from Cook Medical, Speakersfee Viatris. N Haj Mohammad has served as a consultant for Merck, BMS, Astra Zeneca, Servier and has received institutional research funding from Servier. M.J. Bruno serves as a consultant and receives support for industry and investigator-initiated studies from Boston Scientific and Cook Medical and receives support for investigator-initiated studies from Pentax Medical, 3 M, Interscope, and Mylan. W.J. Lammers acts as a consultant/lecturer for Mediglobe. The remaining authors declare no conflicts of interests.
