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Guidelines for the treatment of cholangiocarcinoma (CCA) are usually reviewed every few years. In this article, we will examine the National Cancer Institute’s Physician Data Query (PDQ) treatment guidelines. This set of guidelines was last updated on September 10, 2021, making it one of the latest guidelines on CCA treatment available at the time of writing. 

The PDQ adult treatment editorial board made the scope of their guidelines clear from the very first paragraph: “This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of bile duct cancers. It is intended as a resource to inform and assist clinicians who care for cancer patients.” 

Importantly, they added, “It does not provide formal guidelines or recommendations for making health care decisions.” However, these guidelines are a reflection of currently available medical literature, and are hence worthy of serious consideration. 

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When Resection is an Option 

When it comes to treatment options for CCA (and indeed, many other cancers as well), the big question is whether the tumor remains resectable. 

Physicians must first make a thorough assessment of the tumor’s extent to determine surgical resectability. The Cholangiocarcinoma Working Group, a coalition of Italian medical bodies, wrote a paper on Italian guidelines for treating CCA. On assessing tumor extent, they wrote, “Disease extent, length of bile duct involvement, presence of metastatic disease, remnant liver volume, and vascular invasion are initially evaluated using computed tomography and/or magnetic resonance imaging [plus] magnetic resonance cholangiopancreatography, while positron emission tomography should be considered to detect occult metastatic disease or lymph node involvement.” 

In other words, this stage of CCA management, namely the assessment of disease extent and the detection of any metastases, must be carried out thoroughly, using the best medical imaging available to the physician.

Read more about CCA diagnosis 

Let’s look at our options when it comes to resectable CCAs. “Among patients treated with surgical resection, long-term prognosis varies depending on primary tumor extent, margin status, lymph node involvement, and additional pathologic features,” the PDQ editorial board wrote. In essence, no 2 resectable CCAs are the same.

It is generally good news if a tumor remains resectable, as “the goal of curative surgical treatment is resection with negative margins,” according to the Italian Cholangiocarcinoma Working Group.

Read more about CCA treatment 

To ensure that resection is performed as cleanly as possible, resection of the adjacent liver may also be performed. If the hepatobiliary surgeon determines that major hepatic resection is necessary, postoperative hepatic reserve should be assessed. Physicians should determine the Child-Pugh score and the Model for End-Stage Liver Disease score for CCA patients with underlying cirrhosis.

Liver transplant is also a treatment option for patients with resectable CCA. Initially, high recurrence rates dampened enthusiasm for this course of action. However, a large study involving 216 patients with unresectable perihilar CCA who underwent neoadjuvant chemotherapy followed by liver transplantation had an impressive 5-year disease-free survival rate of 65%. The appropriateness of this highly invasive procedure largely depends on the judgment of the treating surgeon, as well as whether patient consent is obtained.

Managing Unresectable Disease

And what about unresectable disease? Most cases of intrahepatic, distal, and perihilar CCA cannot be completely resectable because they tend to invade adjacent structures, such as the portal vein, the common bile duct, adjacent lymph nodes, and the adjacent liver. In metastatic CCA, one of the most common sites of metastasis is the peritoneum. In unresectable disease, resection of what’s surgically possible may not be enough to stop disease recurrence within the hepatobiliary system or at distant sites.

The Italian Cholangiocarcinoma Working Group presented a list of options in the case of unresectable disease.

“When surgical resection is contraindicated in patients with liver-predominant CCA, locoregional therapies may be considered in order to delay disease progression and prolong life or as a bridge to curative treatment (ie, downstaging),” they wrote. “For iCCA, transarterial chemoembolization, drug-eluting bead transarterial chemoembolization, radiofrequency ablation, microwave ablation, transarterial radioembolization, and reversible electroporation have been evaluated, all with varying advantages and disadvantages and with their use dependent on local availability and experience.”

All of these therapies, either alone or in combination with chemotherapy, have been shown to improve clinical outcomes in patients with unresectable CCA. 

Another strategy, recommended by the PDQ editorial board, is to improve local control and potentially downstage the tumor for surgical resection through chemoradiotherapy. However, the PDQ editorial board cautioned that the curative potential of this procedure is still unknown. 

“For patients with unresectable bile duct cancer, management is directed at palliation,” they wrote.

On first-line chemotherapy, the Italian Cholangiocarcinoma Working Group is firmly behind the combination of cisplatin and gemcitabine. They wrote, “Robust data supports the use of first-line cisplatin/gemcitabine chemotherapy in patients with advanced disease. (Strength of recommendation: strong in favor; quality of evidence: high).” 

Another form of palliative therapy is the relief of biliary obstruction, especially when patients are symptomatic.

“Relief of biliary obstruction is warranted when symptoms such as pruritus and hepatic dysfunction outweigh other symptoms of the cancer,” the PDQ editorial board wrote. “When possible, such palliation can be achieved with the placement of bile duct stents by operative, endoscopic, or percutaneous techniques.”

The Value Of Guidelines 

Guidelines such as the ones detailed in this article allow physicians to make better clinical decisions based on available medical literature and the experience of other physicians worldwide. The beauty of guidelines is that they are not rigid. In fact, they are far from it, often adapted according to the best and latest evidence, meaning there is always an opportunity to expand one’s horizons and reexamine long-held standards of care.


PDQ® Adult Treatment Editorial Board. Bile Duct Cancer (Cholangiocarcinoma) Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Updated September 10, 2021. Accessed November 28, 2021.

Cholangiocarcinoma Working Group. Italian clinical practice guidelines on cholangiocarcinoma – part II: treatment. Dig Liver Dis. 2020;52(12):1430-1442. doi:10.1016/j.dld.2020.08.030

Hassoun Z, Gores GJ, Rosen CB. Preliminary experience with liver transplantation in selected patients with unresectable hilar cholangiocarcinomaSurg Oncol Clin N Am. 2002;11(4):909-921. doi:10.1016/s1055-3207(02)00036-4