At the 2024 CCA Summit, presenters debated on whether to use surgery, transplant, or hepatic arterial pump for localized multifocal biliary tract cancer (BTC). Ashton A. Connor, MD, PhD, first presented on using surgery for treatment of localized multifocal intrahepatic cholangiocarcinoma (iCCA). Dr Connor stated that surgery has the largest effect on mortality over time. He described a study that used an international database across 13 institutions of 514 patients with CCA to create a nomogram to stratify ahead of surgery what the probable outcome is for patients. This nomogram included 6 independent prognostic markers. Results showed that in appropriately selected patients, multifocal disease is not prognostically surgically prohibitive.1
Dr Connor then discussed surgical approaches to optimize outcomes for patients. One study, using a national database across 12 institutions, gathered data on poor survival outcomes on 212 resections.1 The investigators found that the R1 margin was associated with poor survival outcomes only in patients with N0 and that median survival may be correlated with margin width. Regarding minimally invasive surgery, a meta-analysis was conducted across 8 studies that included 2800 patients with BTC who either underwent laparoscopic surgery (n=544) or open resection (n=2256). Results indicated that there were no significant differences in the overall survival (OS) between both types of surgeries or different baseline characteristics between laparoscopic hepatectomy and open hepatectomy in the included studies.1
Lastly, Dr Connor discussed using adjuncts with surgery such as neoadjuvant therapy, adjuvant therapy, and molecular profiling to optimize survival outcomes. One study analyzed data from the National Cancer Database from 2006-2014 and found that out of 881 patients with CCA, 8% had neoadjuvant therapy before resection, and the majority of patients who received chemotherapy received multiagent chemotherapy.1 The analysis revealed that neoadjuvant chemotherapy improved post-resection survival in stage II-III cases. The BILCAP trial was a phase 3, randomized control trial that included 223 patients with resected BTC who received adjuvant capecitabine. The study found that recurrence-free survival was improved; however, there was no change in OS. Dr Connor then discussed the role of molecular profiling in patients with CCA. A study from Memorial Sloan Kettering Cancer Center (MSKCC) and Erasmus MC Cancer Institute analyzed 412 cases and 198 resections and found that molecular profiling alone is approximately as powerful as clinical profiling.1 The molecular alterations were associated with poorer outcomes in resected iCCA.
Alice C. Wei, MD, MSc, FRCSC, argued that pump is best when comparing transplant versus surgery versus pump for multifocal iCCA. A hepatic arterial infusion (HAI) pump is a surgically implanted device that delivers chemotherapy directly to the liver through the gastroduodenal artery.2 She described a post-hoc study of 268 patients at 3 centers with unresectable, locally advanced iCCA that compared patients treated with systemic gemcitabine-cisplatin (Gem-Cis) versus HAI pump delivering floxuridine plus Gem-Cis. There was a total of 68% of patients who had multifocal tumors and 53% were regional lymph–node positive. Patients who received HAI pump chemotherapy had an OS of 28 months versus 12 months in patients who received Gem-Cis only.2
Dr Wei argued that surgical resection as a primary treatment of multifocal disease is uncommon. One study directly compared HAI pump chemotherapy versus resection for patients with multifocal iCCA. This study was carried out from 2001-2018 and included 178 patients who underwent resection and 141 patients who underwent hepatic artery pump placement. There was no difference in median OS between the 2 cohorts (HAI pump: 20.3 months vs resection: 18.9 months).2
Dr Wei then discussed transplant eligibility, arguing that most patients are not eligible for transplant and, therefore, HAI pump would be a better universal option. A study was conducted in all patients evaluated for immunohistochemistry at MSKCC from 2008-2018.2 This study applied liver transplant eligibility criteria to retrospectively determine transplant eligibility. Results showed that only 2% of all patients evaluated for iCCA were potentially transplant-eligible.2
Dr Wei argued that HAI pump plus systemic therapy should be first-line therapy for multifocal iCCA. She stated that surgical resection does not offer benefit over HAI pump and most patients are not eligible for liver transplant. HAI pump therapy does not preclude surgical resection or liver transplant and can be used as a conversion or bridging therapy.2
Keri E. Lunsford, MD, PhD, FACS, argued for liver transplant for localized multifocal disease. She stated that surgical resection is currently the gold standard for treatment of iCCA; however, the indications for resection include no extrahepatic disease, no distant nodal metastasis, solitary lesion is ideal, and adequate future liver remnant with no cirrhosis.
Approximately 15% of patients with iCCA undergo resection and there is 60% to 70% of recurrence following resection.3 Dr Lunsford argued that liver transplant achieves tumor-free margins, treats parenchymal invasion, removes the underlying tumor, and treats treatment-related liver toxicity and biliary structures. A retrospective multinational analysis of cirrhotic patients untreated or treated with locoregional therapy found that liver transplant is reasonable for patients with “very early” iCCA with tumors no larger than 2 cm. The 5-year OS in patients with ≤2 cm solitary tumors was 65% compared with patients with multiple tumors or a tumor greater than 2 cm (45%).3
Dr Lunsford discussed data from the first 6 patients with locally advanced, unresectable iCCA who received a liver transplant at a single liver transplant center.3 At 1 year there was 100% OS and 50% recurrence-free survival, and at 3 to 5 years there was 83.3% OS and 50% recurrence-free survival. Data from 3 patients who had recurrence revealed that 1 patient had positive perihilar fat margin, 1 patient had isolated pulmonary metastasis, and 1 patient had a stable bony lesion on pre-outcome of patients after orthotopic liver transplantation imaging. She highlighted that patient selection for transplant needs to be very critical.3
Dr Lunsford discussed that iCCA may be an acceptable indication for transplant in select patient populations.3 She stated that tumor biology is critical for proper patient selection for transplant. Next-generation sequencing testing should be performed for both risk stratification and potential targeted therapeutics. Transplant does not exclude other treatment options for initially resectable disease.3
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