E272: Has management of locally advanced intrahepatic cholangiocarcinoma evolved with the evidence? Trends and practice patterns from the National Cancer Database

Mounting evidence suggests a limited role for surgical resection in intrahepatic cholangiocarcinoma (IHC) with multifocal hepatic or regional lymph node involvement. This study characterizes trends and practice patterns in the management of locally advanced IHC without distant extrahepatic metastasis.

Methods:

We queried the National Cancer Database (NCDB) for patients with IHC 2004-2020. Patients with non-invasive disease, other primary cancers, distant metastasis (M1), unknown M status (MX), and no treatment were excluded. Lymph node involvement was categorized using clinical N stage to reflect clinical decision-making. Due to AJCC staging updates, subgroup analysis of multifocal disease (7^th AJCC edition T2bNXM0) was confined to 2010-2017. Time trends were evaluated using a two-sided Cochran-Armitage test. Overall survival (OS) was summarized using Kaplan Meier methods.

Results:

Of 11368 patients treated for IHC without distant metastasis, clinical lymph node staging was available for 10183, of which 24% (n=2467) had positive nodes. The multifocal disease subgroup comprised 1384 patients staged T2bNXM0 between 2010-2017. Overall, 36% of patients received formal resection as first treating modality and 59% received systemic or radiation therapy first; the remaining 5% received local tumor destruction, transplant or surgery other than formal resection first. Use of perioperative chemotherapy in combination with formal resection increased from 39% pre-2010 to 70% in 2018-2020 (p< 0.001), most often delivered post-operatively: 49% received adjuvant, 13% neoadjuvant, and 8% both in 2018-2020. Among those with clinically positive lymph nodes, there was a decreasing trend in upfront resection (p< 0.001) and an increase in systemic or radiation therapy first (p< 0.001). Similarly, in the multifocal disease subgroup, upfront resection trended down from 33% in 2010 to 12% in 2017 (p< 0.001). Across the entire cohort, median OS improved from 16 (IQR 15, 18) to 27 (IQR 26, 29) months for patients diagnosed 2018-2019 compared to pre-2010.

Conclusions:

Major trends in the management of IHC without distant extrahepatic metastasis include increasing use of perioperative systemic therapy combined with formal resection versus resection alone and an improvement in overall survival. On subgroup analysis, there was a significant and appropriate trend away from resection as first treatment modality for patients with clinically positive lymph nodes or multifocal disease.