Cholangiocarcinoma, an aggressive bile duct cancer that’s being reported more frequently—especially among Asian people and people over 65 years old—is already a tough disease to treat, given its 5-year survival rate of less than 5%.

Yet a confusing system of sub-disease codes makes it even harder for doctors to get a handle on this devastating cancer. This leads to inaccurate reporting of the number of cholangiocarcinoma cases worldwide, says renowned liver specialist Shahid Khan, MBBS, PhD.

“We always think increasing awareness or environmental factors might be driving up the incidence. However, when you look at the data, not all cholangiocarcinomas are increasing—only one particular subtype. If it was awareness of the disease overall, that shouldn’t happen,” said Dr. Khan, a hepatology professor at Britain’s Imperial College London.

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“And if we’re getting better at diagnosing it, then we should be picking up the cancer earlier and more quickly,” he told Rare Disease Advisor. “That should lead to improved survival at an earlier stage of the diagnosis. But that has not happened.”

Dr. Khan recently addressed the Cholangiocarcinoma Foundation’s 2022 Annual Conference on this subject. He will also speak at the next meeting of the European Network for the Study of Cholangiocarcinoma (ENS-CCA), set for July 7-8, 2022, in Edinburgh, Scotland.

Three Distinct Subtypes

Shahid Khan, MBBS, PhD, of Imperial College London, is a British expert on cholangiocarcinoma. Credit: Larry Luxner

About 50% of all cholangiocarcinomas are perihilar (pCCA), meaning they occur around the exit of the bile duct to the liver. Another 20% are intrahepatic (iCCA)—inside the liver itself—and the remaining 30% are distal or extrahepatic (dCCA), meaning that the cancer arises in the bile ducts outside the liver.

“There are 3 distinct anatomical sites of cholangiocarcinoma, and all 3 present differently,” Dr. Khan said. “Their clinical features are different. How one makes a diagnosis might be different, and the treatment is potentially different. The type of surgery might be different, whether it can be stented or not to relieve obstruction.”

“The other thing that we are realizing is that these 3 subtypes have distinct epidemiological trends and distinct mutations. And the mutations that lead to them seem to be different, so is important to know these 3 subtypes.”

No Code for the Most Common Type of CCA

The problem is that the current iteration of the World Health Organization’s International Classification of Diseases, known as ICD-10, has specific codes for iCCA and dCCA, but not pCCA.

“The ICD coding system changes because we get new diseases, or we realize 1 disease might be 2 separate diseases. It’s always evolving,” Dr. Khan said. “Currently, most places in the world are using the 10th version of the ICD system, which does not have a code for pCCA, the most common cholangiocarcinoma.”

“This has been corrected in the new ICD coding, but that hasn’t come out yet,” he said, noting that under ICD-11, pCCA carries the code C18.0, iCCA is designated as C12.10, and dCCA is listed as C15.0. But most countries won’t start using ICD-11 until sometime in 2023.

In the meantime, he said, “the studies that I’ve done have shown that it is probably this perihilar cholangiocarcinoma that’s probably being coded incorrectly as intrahepatic, because there’s nowhere else to put them.”

Dr. Khan and his team individually reviewed 600 cases of cholangiocarcinoma at 3 British hospitals and found that 90% of patients with the perihilar subtype had been incorrectly coded as having intrahepatic cholangiocarcinoma.

But, as he said, “you can’t do that for every case in the world. That’s not feasible.” Complicating the problem is that all countries won’t adopt ICD-11 standards at the same time.

Monitoring, Treatment of CCA Improving

On a positive note, he said, while 60% of cholangiocarcinoma cases still don’t have any known risk factors,“ of the 40% that do, we are a lot more tuned in to monitoring those patients. Looking ahead, [in the] next 5, 10, 15 years we’ll have more accurate coding.”

In addition, liver transplants—which the medical establishment frowned upon for cholangiocarcinoma patients as recently as the early 2000s—are now becoming more commonplace.

“The Mayo Clinic found that if you selected your patients carefully with cholangiocarcinoma, they did very well from a liver transplant. They changed the game,” Dr. Khan said. “Liver transplant—not for all cholangiocarcinoma cases, but for certain cases—is now deemed to be an appropriate treatment.”

In addition, he said, “surgical techniques are getting better for patients whose cholangiocarcinoma can be cured by resection, provided the diagnosis is made early enough, the cancer is localized, and it’s resectable. Then, most patients will end up needing systemic treatment or types of chemotherapy. We have come a long way in the last 20 years.”