Liver: A Neglected and Deadly Cancer

The deadliness of liver cancer is undisputed, but a growing body of data shows that too often, patients, and particularly those who are uninsured or nonwhite, miss out on earlier diagnosis and potentially life-saving surgery.

Charlotte Huff

Liver cancer is the deadly exception. Overall, U.S. cancer death rates have been on a slow, steady decline for decades. But not for liver cancer. Deaths have been increasing by 2.8% annually for men and 2.2% for women, according to an analysis of federal data published in 2016 in the journal Cancer. Nearly 41,000 Americans are diagnosed with liver cancer each year. Fewer than one in five (17.6%) will be alive five years later.

Liver and Intrahepatic Bile Duct Cancer Incidence and Deaths Going Up

Number per 100,000 people

Source: National Cancer Institute, Cancer Stat Facts

Yet there is some good news, if the cancer is caught before it spreads beyond the liver itself, according to Farhad Islami, MD, the American Cancer Society’s strategic director of cancer surveillance research. From 2006 to 2012, 39% of patients with early-stage liver cancers were surviving at least five years, more than twice the five-year survival rate of Americans diagnosed with liver cancer in the early ’90s, according to an analysis of U.S. cancer mortality trends by Islami and a team of researchers.

The encouraging evidence that treatment of liver cancer at an early stage could have a benefit has stirred up some fresh interest in screening that zeroes in on high-risk groups.

But the life-saving potential of earlier detection and treatment has also again revealed an ugly truth about gains against cancer in this country: They are not shared equally.

Consider a study published in the journal HPB in 2015. It showed that about 40% of nearly 44,000 patients with stage 1 or stage 2 hepatocellular cancers (the most common type of liver cancer) got some type of surgical intervention. Patients who got a surgical intervention lived a median of 48.3 months compared with just 8.4 months for those who did not. Those surgical patients were more likely to be white or Asian, earn a higher income, and have health insurance coverage. The researchers found that two factors—health insurance coverage and getting care at an academic medical center—correlated with increased survival.

“If you get in the door, then you’re going to get care regardless of whether you are white, black, rich or poor,” says Shimul Shah, MD, chief of the transplant surgery section of the University of Cincinnati College of Medicine and one of the co-authors of the HPB study. “But what we’ve found over the years is that there are definitely racial and socioeconomic differences with who can get in the door,” he says. “The question is, ‘Why?’”

Growing interest in screening

Liver cancer is an off-the-radar cancer. It’s far less common than lung, breast, or prostate cancer. And it doesn’t have a media campaign whipping up attention for research and treatment. But if mortality were the only factor, liver cancer would rank higher. More Americans are going to die from liver cancer this year than from prostate cancer or leukemia.

The causes are not a complete mystery. Islami was the lead author of a study published in CA: A Cancer Journal for Clinicians earlier this year that traced nearly three fourths of cases to modifiable risk factors, such as hepatitis B and C, high alcohol consumption, and smoking. The risk factors are modifiable because people can cut back on alcohol consumption and quit smoking. Hepatitis C can be cured with antivirals like Sovaldi, and the CDC now recommends that baby boomers get tested for the disease. There’s a vaccine against hepatitis B.

Screening people with metabolic syndrome for fatty liver disease should be studied, says Ahmed Kaseb, MD.

The American obesity epidemic isn’t helping matters. Excess weight has been linked to about a third of all liver cancers. Ahmed Kaseb, MD, who directs the liver cancer program at Houston’s M.D. Anderson Cancer Center, says most of his patients are “people who show up with this metabolic syndrome picture who’ve been walking around 20 to 30 years carrying probably fatty liver and then eventually, for sure, liver cirrhosis without even knowing.”

Kaseb wants to conduct a study, partnering with an employer, to offer ultrasound screening to workers with metabolic syndrome to determine how many have unknowingly developed a fatty liver or other changes that increase their liver cancer risk.

At this point, no medical groups recommend routinely screening people at average risk for liver cancer. And the benefits of screening are debatable even when screening is limited to a far smaller group of high-risk individuals.

In guidelines published earlier this year, the American Association for the Study of Liver Diseases (AASLD) said that individuals with cirrhosis should get ultrasound screening every six months and possibly also a blood test that checks for elevated levels of a marker called alpha-fetoprotein. Prior AASLD guidelines, which focused on adults with hepatitis B, recommended screening every six to 12 months and emphasized using ultrasound.

But the 2018 guidelines also reference “some controversy” about the mortality benefit of screening people with cirrhosis because randomized studies haven’t been done in Western populations.

Shah acknowledges the uncertainty about screening. At the same time, he sees a reason for it. “Liver cancer is relatively asymptomatic—if it becomes symptomatic, they’re going to die soon,” Shah says. “So if we say we’re not going to screen anyone, we’re going to have a lot of advanced cancer.”

Evidence of disparity

Differences in survival rates are one clue that access to early treatment for liver cancer is far from equal. Islami and his colleagues published an analysis in CA: A Cancer Journal for Clinicians that found that 46% of Asians with localized liver cancer—diagnosed before it has spread to the lymph nodes or elsewhere in the body—survived at least five years compared with just 30% of blacks, 34% of Hispanics, and 36% of whites.

Blacks are less likely to get surgery for early-stage liver cancer than other groups, according to research by Shimul Shah, MD.

Shah and his colleagues also have found treatment disparities after digging into the data about people diagnosed with early-stage liver cancer. For example, they reported results in 2015 in the journal Surgery, showing that black patients were less likely to get surgery than Asians or whites, even when there was no difference in their tumor size or stage.

In another study published last year, they found that patients at safety net hospitals were treated differently than patients at other hospitals. Specifically, among patients with stage 1 or 2 liver cancer, slightly more than half (50.7%) of the safety net patients were treated with surgery compared with two thirds (66.7%) of the stage 1 and 2 patients at other hospitals. The safety net patients also faced a higher likelihood of poor postsurgical outcomes, including readmission or death. However, Shah and his colleagues found that among those who survived past the first month, the long-term survival was similar to those treated at other hospitals.

Specialized liver centers are relatively rare. Shah says that patients with lower incomes might have difficulty accessing care at one of those centers. Perhaps part of the response to disparity in liver cancer treatment should focus on safety-net hospitals and their treatment of patients with early-stage malignancies, he said. In that way, all patients might have an equal shot at potentially curative treatment for a devastating diagnosis.

Charlotte Huff is a freelance health and business journalist in Fort Worth, Texas. She has written for Health Affairs, Kaiser Health News, and Stat among many other publications.

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