Metastatic lymph node burden and invasive tumour features inform first recurrence patterns after curative-intent resection for intrahepatic cholangiocarcinoma.

BACKGROUND

Recurrence is a major driver of poor long-term outcomes after curative-intent resection for intrahepatic cholangiocarcinoma (iCCA), yet the association between postoperative pathology, first recurrence patterns, and post-recurrence outcomes remains unclear.

METHODS

Patients who underwent curative-intent resection for iCCA (2000-2023) were identified from an international multi-institutional database. First recurrence patterns were classified as intrahepatic-only, extrahepatic-only, or combined intrahepatic and extrahepatic recurrence. Multivariable analyses assessed associations between postoperative pathological features, first recurrence patterns, post-recurrence survival (PRS), and post-recurrence curative-intent treatment.

RESULTS

Among 1328 patients, 763 patients (57.5%) developed a recurrence; 717 patients had a classifiable first recurrence pattern (381 patients developed intrahepatic-only recurrence, 171 patients developed extrahepatic-only recurrence, and 165 patients developed combined intrahepatic and extrahepatic recurrence). Three or more metastatic lymph nodes (adjusted OR (aOR) 3.47 (95% c.i. 1.56 to 7.72)) and microvascular invasion (aOR 2.49 (95% c.i. 1.61 to 3.85)) were associated with higher odds of combined recurrence compared with intrahepatic-only recurrence, whereas perineural invasion (aOR 2.24 (95% c.i. 1.35 to 3.71)) and the absence of pathological nodal evaluation (aOR 2.04 (95% c.i. 1.24 to 3.36)) were associated with extrahepatic-only recurrence. Compared with intrahepatic-only recurrence, combined recurrence was associated with worse PRS (adjusted HR 1.63 (95% c.i. 1.29 to 2.06)) and lower odds of receiving curative-intent treatment (aOR 0.14 (95% c.i. 0.06 to 0.29)).

CONCLUSION

Pathological nodal burden and invasive tumour features were associated with distinct first recurrence patterns after iCCA resection. Combined recurrence, more common with ≥3 metastatic lymph nodes or microvascular invasion, was associated with worse PRS and lower receipt of curative-intent treatment. Among patients who develop recurrence, pathological prognostic factors available after surgery may help characterize first recurrence patterns and inform risk-adapted postoperative surveillance.