Recurrence Rate and Pattern of Perihilar Cholangiocarcinoma after Curative Intent Resection

Abstract

Background: The aim of this study was to investigate the rate and pattern of recurrence after curative intent resection of perihilar cholangiocarcinoma (PHC).

Study design: Patients were included from 2 prospectively maintained databases. Recurrences were categorized by site. Time to recurrence and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to identify independent poor prognostic factors.

Results: Between 1991 and 2012, 306 consecutive patients met inclusion criteria. Median overall survival was 40 months. A recurrence was diagnosed in 177 patients (58%). An initial local recurrence was found in 26% of patients: liver hilum (11%), hepaticojejunostomy (8%), liver resection margin (8%), or distal bile duct remnant (2%). An initial distant recurrence was observed in 40% of patients: retroperitoneal lymph nodes (14%), intrahepatic away from the resection margin (13%), peritoneum (12%), and lungs (8%). Only 18% of patients had an isolated initial local recurrence. The estimated overall recurrence rate was 76% at 8 years. After a recurrence-free period of 5 years, 28% of patients developed a recurrence in the next 3 years. Median RFS was 26 months. Independent prognostic factors for RFS were resection margin, lymph node status, and tumor differentiation. Only node-positive PHC precluded RFS beyond 7 years.

Conclusions: Perihilar cholangiocarcinoma will recur in most patients (76%) after resection, emphasizing the need for better adjuvant strategies. The high recurrence rate of up to 8 years justifies prolonged surveillance. Only patients with an isolated initial local recurrence (18%) may have benefited from a more extensive resection or liver transplantation. Node-positive PHC appears incurable.

Figure 1

Cumulative probability of recurrence (local or distant) after curative intent resection for perihilar cholangiocarcinoma with number of patients at risk. (A) All patients; (B) margin wide, narrow, or positive, p=0.002; (C) N0 (node-negative with at least 4 evaluated lymph nodes), Nx (node-negative with less than 4 evaluated lymph nodes), vs N1 (node-positive), p<0.001; (D) well versus moderately or poorly differentiated tumor, p<0.001.

Figure 1

Cumulative probability of recurrence (local or distant) after curative intent resection for perihilar cholangiocarcinoma with number of patients at risk. (A) All patients; (B) margin wide, narrow, or positive, p=0.002; (C) N0 (node-negative with at least 4 evaluated lymph nodes), Nx (node-negative with less than 4 evaluated lymph nodes), vs N1 (node-positive), p<0.001; (D) well versus moderately or poorly differentiated tumor, p<0.001.

Figure 1

Cumulative probability of recurrence (local or distant) after curative intent resection for perihilar cholangiocarcinoma with number of patients at risk. (A) All patients; (B) margin wide, narrow, or positive, p=0.002; (C) N0 (node-negative with at least 4 evaluated lymph nodes), Nx (node-negative with less than 4 evaluated lymph nodes), vs N1 (node-positive), p<0.001; (D) well versus moderately or poorly differentiated tumor, p<0.001.

Figure 1

Cumulative probability of recurrence (local or distant) after curative intent resection for perihilar cholangiocarcinoma with number of patients at risk. (A) All patients; (B) margin wide, narrow, or positive, p=0.002; (C) N0 (node-negative with at least 4 evaluated lymph nodes), Nx (node-negative with less than 4 evaluated lymph nodes), vs N1 (node-positive), p<0.001; (D) well versus moderately or poorly differentiated tumor, p<0.001.