How Liver Cancer Is Screened and Staged for Patients

In this interview for October’s observation of Liver Cancer Awareness Month, Dr. Anjana Pillai explains how liver cancer is screened for, diagnosed, staged and confirmed in the least invasive ways possible, and what questions patients should ask after diagnosis.

Dr. Anjana Pillai is a professor of medicine and surgery and leader of multiple liver programs at UChicago Medicine.

CURE: How are specific stages diagnosed, and how do they differ from each other?

Pillai: If you're part of a screening protocol — patients specifically hepatitis B — you should be undergoing surveillance or screening for liver cancer. Right now, guideline recommendations are imaging of your liver with a good ultrasound and a biomarker called AFP, or alpha-fetoprotein. Studies have shown that combining the two actually increases the detection of liver cancer. And again, you're trying to do it early.

Now, these are for people with known risk factors. We’re focusing on HCC. In patients at risk for bile duct cancer, there are different types of bile duct cancer. One is called hilar or perihilar cholangiocarcinoma, and the main risk factor is PSC, or primary sclerosing cholangitis. So similarly, if you have a chronic liver disease, you’d be in a screening protocol. However, there are lots of patients, unfortunately, who develop bile duct cancer — cholangiocarcinoma — who don’t have risk factors, and that’s a harder population because you don’t yet know who is at risk in those instances.

What types of imaging or blood tests are used to help diagnose currently?

Surveillance usually starts with the ultrasound and AFP — fairly easy tests, very noninvasive. AFP, or alpha-fetoprotein, is a blood biomarker. Now, the caveat is 30% to 40% of patients may not produce AFP, so the ultrasound component is also very important.

Now, if a cancer is detected — something abnormal in the liver — or your AFP is very high and it doesn’t make sense why that should be, but we can’t quite see a mass, then we do further testing. Usually those are cross-sectional imaging: a dynamic triphasic CT scan of the liver or an MRI of the liver. Those tests involve contrast, and they are two different types of contrast, but the idea is you’re getting a CT or MRI with contrast. When I say dynamic or triphasic, that just refers to the timing and the way the contrast is administered.

Those tests will then define: OK, do I have liver cancer? For the vast majority, at least, it will give you an idea — is there a mass in my liver, what does it look like, is it pointing toward liver cancer? And then based on that, you do other appropriate testing.

Can you explain what staging is and why it’s important in the simplest terms for patients?

If it looks like someone has a primary liver cancer — some cancers, very few like HCC, don’t necessarily need a biopsy if the imaging characteristics are very classic in the background of cirrhosis or chronic hepatitis B. The vast majority of those patients, if you do a CT or MRI with contrast, have these specific characteristics.

Once you confirm that, then based on size, number, location, extent, you will also need to do further testing like a CT scan of the chest to make sure it hasn’t gone elsewhere. Bone and chest are the most common places that liver cancers can go. So that’s what staging means — seeing the size, number, whether it invades major blood vessels or bile ducts, and making sure it hasn’t spread outside the liver.

How does a biopsy help guide treatment decisions?

With primary HCC, many times you can diagnose it based on testing in the right background of advanced liver disease or hepatitis B. However, there are times when it’s not clear, and that’s when a biopsy is important to distinguish: Is this a primary HCC? There are some tumors that are mixed between HCC and cholangiocarcinoma. Or is this actually a cholangiocarcinoma?

And for most other cancers, including if you think someone has intrahepatic cholangiocarcinoma or a hilar cholangiocarcinoma, you do need a tissue diagnosis. That allows you to definitively diagnose the cancer. It also gives you information about tumor differentiation — how early or advanced it is. And then it also allows us to check for something called next-generation sequencing, which is really genetic sequencing, to see if we have specific medications targeted at specific genes that the cancer may produce.

What are some noninvasive ways doctors can assess liver cancer today, if you haven’t already mentioned them?

I think the testing I mentioned — early screening for those who qualify — and then for people who may present incidentally, meaning you don’t have the traditional risk factors and you see something in the liver, making sure you get better-quality testing so we can clearly define it. A really good CT scan or MRI should be able to. People do get nervous about contrast, but in most patients, unless they have an allergy or advanced kidney disease, there’s not much to worry about. There are many ways contrast can be modified, so it’s largely safe.

Contrast and timing of contrast really help us distinguish certain features and help us realize if something is benign or malignant, and help differentiate between these two liver cancers we’re talking about. So those are all noninvasive tests before we talk about invasive testing, which is biopsy.

Speaking about common worries of patients, what questions should patients ask their care team after receiving a diagnosis?

I think it is very important to make sure you understand your diagnosis. Easier said than done, because many patients come to my clinic and are not sure if they have cancer or not. Sometimes providers may say, you have a spot in your liver, a mass, a lesion — that doesn’t necessarily mean cancer to patients. I always clearly define it if I’m saying you do have a primary liver cancer.

First and foremost, you have to understand your diagnosis. And if you don’t, ask questions: What does the mass or lesion mean? If you are able, ask to see the images. In my clinic, we always pull up images so patients can see what I’m talking about, because otherwise it is very abstract.

Another thing is talking about the cancer stage and what that means. Sometimes it’s uncomfortable when it’s advanced cancer, but patients need to know. They need to know their options, if it’s curative or not, if treatments could make it curative one day, or if not, what treatments could prolong life and quality of life. And if someone is in a very bad spot, then palliative care is very important.

Providers may shy away from those harder conversations, but it’s really important to have them early. Patients can ask: What is my diagnosis? Is it certain? How do you know? Can I see the scan? What stage am I? What are my treatments? If not here, is there somewhere else I can go? Are there trials if standard care isn’t enough?

The more you’re informed, the more likely you’ll ask those kinds of questions.

Transcript has been edited for clarity and conciseness.

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