Recurrence after operative management of intrahepatic cholangiocarcinoma

Abstract

Introduction: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC.

Methods: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed.

Results: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥ 5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively.

Conclusion: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Fig 1

Median RFS was 20.2 months (95% CI, 16.4–28.0). Overall 1-, 3-, and 5-year actuarial RFS was 64.2%, 39.0%, and 32.1%, respectively. (Color version of figure is available online.)

Fig 2

Tumor size and nodal status adversely affected the RFS. A, Patients with tumor size ≥5 cm had a worse RFS than those with smaller tumors. B, Patients with N0 disease also had a longer RFS than those with N1 and Nx disease. (Color version of figure is available online.)

Fig 3

Vascular and perineural invasion both predicted poor survival. A, Patients with no vascular invasion, macroscopic, and microscopic invasion had a median RFS of 28.0, 9.6, and 18.1 months, respectively. B, Patients with perineural invasion had a median survival of 11.4 months compared with 21.8 months for patients without such invasion. (Color version of figure is available online.)

Fig 4

RFS declined with an increasing clinical score. The 5-year RFS for patients with scores 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. (Color version of figure is available online.)