Conditions can make the diagnosis and treatment of liver cancer complex, but USC Norris Comprehensive Cancer Center is leading the way.

Each year, about 21,000 men and 8,000 women contract liver cancer in the United States, according to the Centers for Disease Control and Prevention. Liver cancer can be beaten with early diagnosis and effective surgical treatment, But underlying conditions can make it difficult to diagnose.

“The early signs of liver cancer can be very subtle, to the point of being completely asymptomatic,” says Yuri Genyk, MD, professor of clinical surgery at the Keck School of Medicine of USC and surgical director of the liver transplant program at Keck Medicine of USC.

According to Dr. Genyk, most liver cancers develop due to cirrhosis, a disease in which healthy liver tissue is replaced with scar tissue, which prevents the liver from functioning properly. Cirrhosis is, in turn, often caused by the hepatitis C virus. Nonalcoholic steatohepatitis (NASH), which is an inflammatory condition in the liver in which a build-up of fat causes damage, can also cause cancer in the liver, as can hepatitis B.

The presence of these varying conditions in patients with liver cancer is why USC Norris Comprehensive Cancer Center takes a multidisciplinary approach to the disease — engaging expert specialists, advancing treatments and pursuing new research — to customize treatments for each patient.

“Any time you have a disease that requires a lot of medical attention, you need to build subspecialties around the care of that problem,” says Robert Rick Selby, MD, professor of surgery and chief of the division of hepatobiliary, pancreas and abdominal organ transplant at the Keck School, who trains fellows in non-transplant liver surgery.

For liver cancer, he explains, that includes internists; hepatologists; interventional radiologists, who access blood vessels inside the liver to deliver chemotherapy; medical oncologists, who design chemotherapy strategies; and both transplant and non-transplant surgeons.

“Our mature program enables us to fully serve the patient with treatments that are appropriate for the stages of the disease that are presented to us,” Dr. Selby explains.

When patients with liver cancer seek care at USC Norris, their cases are presented at a multidisciplinary tumor board, which reviews each patient’s condition to come up with the best treatment plan.

If surgery to resect, or remove, a portion of the liver is recommended, USC surgeons often use advanced techniques, Dr. Selby says. These include laparoscopy — inserting a lighted tube into the abdomen to enable a smaller incision than traditional surgery and maximum viewing of the operating field — and robotic devices that aid dexterity during the procedure. Surgeons also aim to isolate the liver from the inflow and outflow of blood to have a bloodless procedure, which enables them to best visualize the boundaries of the tumor and the structures they want to preserve.

“Most community hospitals don’t have the expertise to do these types of advanced surgeries, while most university hospitals do,” Dr. Selby says.

For patients who do not have cirrhosis of the liver, Dr. Genyk says, effective minimally invasive treatments to remove cancerous tumors include radiofrequency ablation (RFA) and microwave ablation (MWA). In RFA, various imaging techniques are used to help guide a fine wire carrying an electrical current, which produces heat that destroys the cancer cells. With MWA, imaging techniques guide a needle that uses microwaves to heat and destroy the tumor.

The liver transplant program at Keck Medicine, which just celebrated its 20th anniversary, plays a significant role in liver cancer treatment at USC Norris.

Like other liver cancer treatment options, transplants also require a comprehensive approach. Physicians are involved not only with the actual procedure, but also with pre-transplant evaluation, post-transplant management of the immune system to prevent organ rejection, and long-term care. The USC Norris program has the best patient survival rate in Southern California, and is among the top three such programs in the United States, according to the Scientific Registry of Transplant Recipients.

“Probably the biggest progress in the surgical treatment of liver cancer is through transplant,” Dr. Genyk says. “The survival of those with liver transplants is usually more than 90 percent within the first year, around 80 percent within three years, and around 70 percent after five years. Then it usually plateaus, and patients can live for a long time after transplant.”

In 2015, USC surgeons performed 125 liver transplants, with 40 percent comprised of liver cancer patients, says Jeffrey A. Kahn, MD, associate professor of clinical medicine at the Keck School and liver transplant program medical director, who coordinates patient care.

According to Dr. Kahn, there is a shortage of available livers from cadavers because USC Norris is part of a large transplant area, region 5, which includes California, Arizona, Nevada, Utah, and New Mexico. “People can wait two years for a transplant in this part of the country,” he explains. “We do a lot of procedures geared toward shrinking tumors while they’re waiting; if the tumor gets too big they can’t have a transplant because the tumor often grows back.”

The liver transplant program’s most effective answer to the shortage is the utilization of living donors, who give a portion of their livers for transplant. USC Norris has the only such active program in Los Angeles. Dr. Kahn says that 12 such procedures were performed in 2016, while in previous years there have been as many as 30. USC Norris is also constantly seeking to improve liver cancer care through research.

Anthony El-Khoueiry, MD, associate professor of clinical medicine at the Keck School and chair of the Clinical Investigations Support Office (CISO) at USC Norris, sees the potential for improving treatment options for patients with advanced liver cancer who are not candidates for surgery or liver transplant. He is currently conducting a clinical trial of nivolumab, a drug that stimulates the patient’s own immune system to fight cancer. “It’s showing promise in terms of shrinking tumors, stopping cancer growth, and hopefully allowing for longer lives,” says Dr. El-Khoueiry, who is known nationwide for his clinical research on liver cancer. He notes that the Food and Drug Administration’s approval of liver cancer drugs has been very selective, with only one given the go-ahead in the last 11 years.

Another researcher, Keigo Machida, PhD, an associate professor of molecular microbiology and immunology at the Keck School, is the senior author of a study that has identified the “Achilles’ heel” in cancer therapy. He and his colleagues found that NANOG, a stem cell marker, is scarce in early-stage liver cancer but abounds in stage III, when it promotes the cancer’s spread by rewiring metabolism in the mitochondria — the specialized structures in cells that are their energy factory.

“Even though we treat patients with chemotherapy, those bad seeds [NANOG] survive and force relapse,” says Dr. Machida. “That’s why we would like to target the bad seeds to prevent the cancer from recurring and spreading to other parts of the body.”

Clinical leaders are also looking backwards, across the decades of patients treated at USC Norris, to better predict effective treatments and possibilities of recurrence.

Dr. Selby is currently tracking patients, including those with liver cancer, to determine what have been the most effective treatment approaches given the stage and biology of patients’ tumors. Previous studies, he says, included one examining the psychological and physical impact of liver transplants from living donors on the patients who received them. “The study changed the way we counsel them about side effects or difficult parts of the outcomes from the procedures,” Selby explains.

Similarly, Dr. Kahn is beginning a review of patients who have had transplants to see if he can identify predictors of the recurrence of cancer after the transplant, which a small percentage of patients experience.

“It takes a long time for a program to be able to yield new and useful information in the field,” Dr. Selby concludes. “It means having a lot of physicians to pull data from patient outcomes. That’s one of the most exciting things about this — that the program has matured to the point where it is in position to become a field leader because of the number and breadth of patients we see, the ability to enroll them in clinical trials, and the number of physicians involved.”