Biliary Tract Cancers: Cholangiocarcinoma and Gallbladder Cancer, Symptoms, Diagnosis and Current Treatment Options

What are biliary tract cancers?

Bile is produced in the liver and carried through the bile ducts to the gallbladder and the intestine. Malignant tumours that develop anywhere along this pathway are together called biliary tract cancers. Those arising from ducts inside the liver are called intrahepatic, and those arising at the liver hilum and from ducts outside the liver are called perihilar and distal cholangiocarcinoma; in addition there is gallbladder cancer [1][2][6]. Although treatment approaches are similar, the location of the tumour significantly affects surgery and treatment.

What causes biliary tract cancers? Risk factors

Long-standing inflammation in the bile ducts is the main common mechanism. For cholangiocarcinoma, primary sclerosing cholangitis, congenital bile duct cysts, bile duct stones, liver parasites (especially those transmitted through raw fish in Southeast Asia), cirrhosis, hepatitis B and C, obesity, diabetes and alcohol may increase the risk [3][6]. In gallbladder cancer the most common risk factor is gallstones; however, the great majority of people with gallstones do not develop cancer. A calcified (“porcelain”) gallbladder, gallbladder polyps, obesity and some chronic infections also increase the risk [1][4]. In both groups the risk increases at older ages; the average age at diagnosis is 72 in gallbladder cancer and mostly in the 60s and 70s in bile duct cancer [3][4].

How common are biliary tract cancers?

Biliary tract cancers are a rare group among digestive system cancers; their frequency differs markedly between regions. Cholangiocarcinoma is much more common in Southeast Asia and China, where liver parasites are widespread [3]. In gallbladder cancer the incidence is higher in women; this is thought to be related to gallstones being more common in women [4]. Because it causes no symptoms in the early stage, a significant proportion of cases are detected at an advanced stage [1][6].

What are the symptoms of biliary tract cancers?

• Yellowing of the skin and eyes (jaundice), widespread itching
• Dark urine, pale and fatty stools
• Pain in the upper right part of the abdomen
• Loss of appetite, unexplained weight loss
• Fever and chills (may be a sign of bile duct infection)

The development of jaundice requires urgent evaluation; these symptoms can also be seen in benign conditions such as gallstones [5]. Gallbladder cancer sometimes causes no symptoms and can be found incidentally, by examination of the gallbladder removed in an operation done for gallstones [1].

How are biliary tract cancers diagnosed?

Ultrasound is the first step; contrast-enhanced CT and MRI showing the bile ducts (MRCP) are used for diagnosis and staging. Samples can be taken from the bile ducts with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound; in the same procedure a stent can also be placed to relieve the obstruction [1][2]. The definitive diagnosis is made by pathological examination. The CA 19-9 tumour marker cannot establish the diagnosis on its own; in bile duct obstruction it can also rise for benign reasons and it is most helpful in monitoring treatment [6]. The disease is classified as resectable by surgery, locally advanced and metastatic [6].

Molecular tests

In advanced disease, targetable alterations are looked for in tumour tissue with next-generation sequencing (NGS): FGFR2 fusions, IDH1 mutation, BRAF V600E, HER2, NTRK fusions, RET and MSI-high status [6][12]. It is important for later options that these tests are done before treatment planning begins, preferably during first-line treatment [6].

How are biliary tract cancers treated?

The treatment decision is made by evaluating the location and stage of the tumour, liver function and the patient’s general condition together. Assoc. Prof. Dr. Ali Oğul’s approach is to evaluate patient files in a multidisciplinary tumour board with specialists in hepatopancreatobiliary surgery, gastroenterology and interventional endoscopy, interventional radiology, pathology and radiation oncology.

Surgery and bile drainage

Surgery is the curative treatment option; depending on the location of the tumour, major operations such as liver resection, bile duct resection or a Whipple operation are performed [2][6]. When gallbladder cancer is found incidentally and the depth of invasion is suitable, it is usually completed with a second operation (extended cholecystectomy) that also includes the liver bed and regional lymph nodes [1][6]. In very selected patients with perihilar cholangiocarcinoma, liver transplantation within a protocol can be considered in specialised centres [2][6]. If there is jaundice, a stent by ERCP or percutaneous drainage is placed before surgery or in patients who cannot be operated on; control of infection and liver function is also important for suitability for chemotherapy [1][2].

Treatment after surgery (adjuvant)

In completely resected biliary tract cancers, six months of capecitabine after surgery showed a survival benefit compared with observation in the BILCAP trial and is recommended as standard in guidelines [6][8].

Inoperable or metastatic disease

In the first line, the combination of gemcitabine and cisplatin is the basic chemotherapy [7]. Adding durvalumab (TOPAZ-1) [9] or pembrolizumab (KEYNOTE-966) [10] to this combination increased survival; both immunotherapies have been approved by the US Food and Drug Administration (FDA) for this indication [11]. In patients who progress after the first line, in the second line chemotherapies such as FOLFOX [6] and targeted drugs determined by the molecular characteristics of the tumour are considered:

• FGFR2 fusion: pemigatinib and futibatinib [12][13]. The FDA also approved lirafugratinib in this group in September 2026 [18].
• IDH1 mutation: ivosidenib prolonged progression-free survival compared with placebo [14].
• HER2 positivity (IHC 3+): zanidatamab (HERIZON-BTC-01) [15] received accelerated approval from the FDA; the objective response rate in HER2 IHC 3+ patients covered by the approval was reported as 52% [17]. For HER2-positive solid tumours, there is also a tumour-agnostic FDA approval for trastuzumab deruxtecan [19].
• BRAF V600E mutation: dabrafenib with trametinib [16].
• NTRK fusion: TRK inhibitors such as larotrectinib or entrectinib [12].
• MSI-high tumours: immunotherapy [6].

In selected inoperable patients whose disease is limited to the liver, locoregional methods such as TACE, Y-90 radioembolisation or ablation can be assessed in the multidisciplinary board; the level of evidence for these methods is limited.

Supportive and palliative care

Control of jaundice and itching, prevention of bile duct infections, pain management, nutritional support and psychosocial support are an integral part of treatment. Palliative care can also be provided alongside oncological treatment from the early period of the disease.

Treatment in older age

Biliary tract cancers are more common at older ages [3][4]. In older patients, decisions about surgery and chemotherapy are individualised according to accompanying diseases, liver and kidney function, nutritional status, independence in daily living and care support. When needed, a geriatric assessment is performed together with a geriatrician; dose adjustment and close monitoring are applied.

Access in Türkiye

The TİTCK list of licensed products dated 09.10.2026 includes products containing durvalumab, pembrolizumab, capecitabine, gemcitabine, cisplatin, dabrafenib, trametinib, larotrectinib, entrectinib and trastuzumab deruxtecan; products containing pemigatinib, futibatinib, ivosidenib, zanidatamab and lirafugratinib do not appear in the list [20]. That a drug is licensed does not mean that it is reimbursed by the Social Security Institution (SGK) for every indication; coverage is verified separately from the product information and the current SGK lists.

Latest regulatory updates for this cancer type: Biliary Tract Cancers: Latest Developments

Side effects and follow-up during treatment

Gemcitabine and cisplatin can cause a fall in blood counts, nausea, and effects on the kidneys and hearing; these are managed with dose adjustments and supportive treatments. Immunotherapy can cause immune-related side effects (diarrhoea, skin rash, liver or thyroid disorders). With FGFR inhibitors, high phosphate levels and nail and eye findings may occur; therefore regular eye and blood test monitoring is needed. After treatment, regular follow-up is done with examination, laboratory tests and imaging [6].

Can biliary tract cancers be prevented?

There is no certain way of prevention; however, keeping the conditions that increase the risk under control, that is, maintaining a healthy weight, limiting alcohol and avoiding raw or undercooked fish in regions where liver parasites occur, can reduce the risk [3][4]. In conditions such as symptomatic gallstones and a calcified gallbladder, a physician’s decision about surgical treatment is needed. In high-risk diseases such as primary sclerosing cholangitis, regular surveillance is carried out in specialist centres; there is no screening method for the general population [6].