Bile Duct Cancer Stages: Location, TNM, and Resectability

Bile duct cancer is also called cholangiocarcinoma. The bile ducts form a branching system that carries bile from the liver down to the small bowel. Where a tumor starts in that system decides which staging ruler is used. There is no single stage chart for all bile duct cancer.

The NCI PDQ health professional summary splits the disease three ways. Intrahepatic tumors start inside the liver. Perihilar tumors start at the hilum, where the right and left hepatic ducts leave the liver and join. Distal tumors start further down, in the common bile duct near the small intestine. PDQ puts about 50% of cases in the perihilar region, 40% in the distal region, and 10% inside the liver.

Perihilar tumors also go by an older name, Klatskin tumors. The distal system covers cancers of the cystic duct too. It does not cover sarcomas or carcinoid tumors.

All three systems use TNM, which stands for tumor, node, and metastasis. T describes the main tumor. N describes nearby lymph nodes. M records spread to distant organs. The three letters combine into a stage from 0 through IV.

PDQ reprints its tables from the AJCC Cancer Staging Manual, 8th edition, published in 2017. What follows is a plain reading of those tables.

For intrahepatic tumors, T starts with a size line. T1a is a single tumor 5 cm or smaller with no blood vessel invasion, which is stage IA. T1b is a single tumor larger than 5 cm, still without vessel invasion, which is stage IB.

T2 covers a single tumor that has invaded a vessel inside the liver, or more than one tumor whether or not vessels are involved. That is stage II.

T3 is a tumor that has punched through the visceral peritoneum, the thin lining over the organ, and is stage IIIA. T4 is a tumor that has grown directly into structures outside the liver, and is stage IIIB. Any nodes involved also lands the cancer at IIIB. Distant spread makes it stage IV.

One detail sets this system apart. For intrahepatic tumors, N1 simply means regional node spread is present. The tables do not count the nodes.

The perihilar system swaps size for depth and blood vessels. T1 is a tumor still inside the duct, reaching no further than the muscle layer or fibrous tissue, and is stage I. T2a has moved past the duct wall into the surrounding fat. T2b has moved into liver tissue next door. Either one is stage II.

T3 means the tumor has invaded the portal vein or hepatic artery branches on one side, and is stage IIIA. T4 is more serious. It covers the main portal vein, its branches on both sides, or the common hepatic artery. It also covers second-order bile duct branches on one side when the vein or artery on the opposite side is involved. T4 is stage IIIB.

Here the nodes are counted. One to three positive nodes is N1, making stage IIIC. Four or more is N2, making stage IVA. Distant spread is stage IVB.

The distal system measures how deep the tumor has burrowed into the duct wall. Less than 5 mm is T1. Between 5 mm and 12 mm is T2. More than 12 mm is T3.

T4 is defined by arteries rather than depth: the celiac axis, the superior mesenteric artery, or the common hepatic artery. Any T4 tumor is stage III, whatever the nodes show.

Node counts work as they do at the hilum. One to three positive nodes is N1. Four or more is N2, which pushes T1, T2, or T3 disease to stage IIIA. Distant spread is stage IV.

PDQ opens its staging chapter with a blunt sentence: bile duct cancer is classified as resectable, meaning localized, or unresectable, and that split carries obvious prognostic importance. Formal TNM staging is usually assigned after surgery, once a pathologist has examined what was removed.

The numbers behind that split are sobering. PDQ says total resection is possible in 25% to 30% of tumors that start in the distal bile duct, and that the rate is lower for tumors further up the system. It states that complete resection with clear margins offers the only chance of cure, and that most intrahepatic, distal, and perihilar cases cannot be completely removed.

Location is a large part of why. PDQ points to the closeness of major blood vessels and to tumor spreading widely within the liver.

PDQ lists the tests that map the extent of disease before any operation: liver function tests and other bloodwork, abdominal ultrasound, CT, MRI, and magnetic resonance cholangiopancreatography, an MRI technique that images the ducts themselves. If a person is fit for surgery and the tumor looks removable, surgeons explore directly.

For tumors at the duct bifurcation, PDQ describes extended operations that take adjacent liver, either a lobectomy or removal of parts of segments 4 and 5. When a large liver resection is needed, PDQ says the liver reserve left behind must be assessed first. For people with cirrhosis, that assessment uses the Child-Pugh class and the Model for End-Stage Liver Disease score.

An unresectable label does not end treatment. PDQ groups the options as palliative therapy, chemotherapy, immunotherapy, and targeted therapy. It also names resection, brachytherapy, external-beam radiation, and stenting as measures that keep bile draining and quality of life better.

One drug safety point sits in the same summary. Capecitabine and fluorouracil are broken down by an enzyme made by the DPYD gene. PDQ estimates that 1% to 2% of people carry inherited DPYD variants that reduce that enzyme's function, which lets these drugs build up in the body.

PDQ also flags factors linked to worse outcomes: involved lymph nodes, perineural invasion, a history of primary sclerosing cholangitis, and a raised CA 19-9 level.

Staging vocabulary in general is covered in cancer staging. Background on the disease itself is in bile duct cancer, and the options that follow a stage are in bile duct cancer treatment.

• NCI PDQ: bile duct cancer, health professional version