Locoregional treatments for biliary cancer: Intra-arterial chemotherapy and primary percutaneous stenting

Biliary cancer is a rare disease with a poor prognosis. Patients are mostly ineligible for surgical resection due to distant metastases, locally advanced disease, or poor performance status. These patients often develop jaundice, because the tumor blocks the bile ducts. To resolve this, one or more biliary stents need to be placed. Endoscopic drainage is standard care internationally. The stent placement is performed via the bowel. Unfortunately, patients often develop pancreatitis and recurrent cholangitis after this procedure, due to bacterial colonization of the bile ducts. Consequently, most patients require multiple reinterventions. The 90-day mortality rate after palliative drainage is 35%, and only 20% become eligible for any palliative systemic treatment. Only after adequate biliary drainage without cholangitis patients with biliary cancer typically qualify for palliative chemotherapy, targeted treatments, and immunotherapy.

In a phase II trial, the TESLA trial, we performed primary percutaneous stenting where biliary stents are placed directly into the bile ducts without crossing the ampulla and without leaving an external biliary drain. In 67 patients, no cholangitis or pancreatitis was observed. Primary percutaneous stenting for palliative patients had a low incidence of drainage-related complications and reinterventions. No drainage-related 90-day mortality was observed. Most patients (61.2%) started with palliative systemic treatment.

In another phase II trial, the PUMP II trial, we performed hepatic arterial infusion pump (HAIP) chemotherapy. This is a treatment with chemotherapy (floxuridine) delivered directly into the liver. A subcutaneous pump is surgically implanted. This pump is connected to the artery leading to the liver, allowing almost no chemotherapy to enter the rest of the body, resulting in minimal side effects for the patients. This treatment originally comes from the Memorial Sloan Kettering Cancer Center in New York. However, systemic chemotherapy (gemcitabine and cisplatin) is the standard care internationally, with a median overall survival of 12 months. During our study, HAIP chemotherapy was given in addition to the standard treatment. In 50 patients, the median overall survival was 23 months, and 1 in 3 patients is still alive after 3 years, compared to only 3% with the standard care.