Transplantation within 6 months of registration does not enhance survival for patients with perihilar cholangiocarcinoma

Objectives: Determine if timing of transplantation affects patient mortality. Background: Neoadjuvant therapy and liver transplantation has emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known. Methods: We reviewed all patients registered for a standardized pCCA protocol between 1996 – 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256). Results: The median (interquartile range) time from registration to transplant or drop out was 5.74 (3.25-7.06) months. Compared to a short wait time (0-3 months), longer waiting times did not affect all-cause mortality: (3-6 months) hazard ratio (HR) 0.98; 95% CI 0.52-1.84; (6-9 months) HR 0.80; 95% CI 0.39-1.65; (9-12 months) HR 0.56; 95% CI 0.26-1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR 0.97; 95% CI 0.67-1.42; AB or B blood group HR 0.93; 95% CI 0.62-1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR 0.92; 95% CI 0.87-0.97). This benefit began after a 6 month waiting time minimum (HR 0.53; 95% CI 0.26-1.10) and increased further after 9 months (HR; 0.43 95% CI 0.20-0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI 0.98-1.00). Conclusions: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival.