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Study reveals strongest link yet between organ transplants, cancer

New research arms doctors with more information that could lead to reduced risk

By Andrea K. Walker, The Baltimore Sun

November 26, 2011

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The most comprehensive study ever on the link between organ donations and cancer is arming physicians with new data that could help make the procedures safer.

Organ transplant patients get new kidneys, livers and lungs that save their lives, but they face a heightened risk of cancer because drugs that prevent the rejection of new organs also weaken the immune system.

Most patients, like Jessica Protasio of Columbia, go through with transplants because the immediate risk of dying from failing organs outweighs the long-term risk of cancer.

"My option at the time was to live or die," said Protasio, who received a liver transplant in March at the University of Maryland Medical Center.

But the research from the National Cancer Institute in Rockville could lead to safer medications and procedures.

The study looked at more than 175,000 transplant patients and found they were twice as likely to get cancer as the general population. Researchers found more than 30 cancers that were more common in transplant patients than in the rest of the population.

"One of our goals is to understand why cancer develops and increase our knowledge of what causes it to occur so that we can make transplant safer," said Eric A. Engels, the lead researcher on the study.

Past studies, more narrowly defined and smaller in size, probably didn't account as accurately for less common cancers. They might look at one group of patients, such as kidney transplant patients, and have far fewer examples. Most of the studies look at kidney transplants, which are the most common.

The NCI study, published in the Journal of the American Medical Association, used data from the Scientific Registry of Transplant Recipients, which tracks every organ transplant in the country. Researchers compared the information to 13 state databases that tracked cancer cases.

"This quantifies it better, which is really important," said Dr. Dorry Segev, the director of clinical research and transplant surgery at the Johns Hopkins School of Medicine, who has seen the study. "This opens the door for a lot of important questions to be answered with regards to who the patients are that are at risk and when the risk seems to emerge so we can do screening then."

The NCI study reinforced much of what had been found in smaller studies. Transplant patients are most likely to get cancers caused by viruses, which are able to break through the body's weakened immune system.

The most common cancers were non-Hodgkin lymphoma, which affects the immune system, and cancers of the lung, liver and kidney. These cancers made up 43 percent of all cancers in organ transplant patients, compared with 21 percent in the general population.

Doctors don't want to scare patients away from transplants, but use the research to better treat patients.

"It's not so common it means people should not get transplants," Engels said. "In the great majority of cases people never get cancer."

Engels said there are many theories about why cancer risk increases for transplant recipients.

The most common issue is the drugs that weaken the immune system, also seen in HIV patients. Studies have shown that HIV patients are two to 10 times more likely to get some cancers.

But from simply looking at the databases, Engels and the other researchers couldn't tell whether other factors contributed. Perhaps the very disease that created the need for a transplant predisposed the person to cancer. So the patient might have gotten cancer even without a transplant.

The NCI study found that lung cancers were most often found in the remaining original lung. Research has shown that cancers found in the first six months after a transplant could be "delayed reports of cancer found in the [removed] lung," according to the study.

Dr. Jonathan Bromberg, head of the Division of Transplantation at the University of Maryland Medical Center, applauded the new research. But he said it would have been even better if it had compared transplant patients to those who have the disease but did not receive transplants.

"If you have chronic kidney disease, if you are on dialysis, you have a higher chance of getting cancer," Bromberg said.

"Just having chronic organ failure can also affect your immune system to make you susceptible to certain kinds of tumors," he added.

Another question is what causes the cancers that are not virus-related, such as cancers of the kidney, skin and liver.

"We are going to have to do more work to sort out all of the possible explanations," Engels said. "There are a number of factors that could explain some of these cancers."

Paul McSorley was told about the potential for cancer before he got a kidney transplant in June. He said the doctors were very direct and asked how it made him feel.

"I wasn't crazy about it," said the 55-year-old who lives in Fallston. "But it's better than being married to a dialysis machine. And the other trade-off, of course, is a shorter life or imminent death."

McSorley, who needed a transplant after complications from diabetes and hypertension destroyed his kidneys, said his quality of life improved with the transplant. So far he is cancer-free.

Protasio became gravely ill last year with abdominal pain that made it hard for her to get out of bed. Testing revealed liver cancer, which doctors tried to remove surgically. But when they opened her up they discovered that the tumor was too big. A transplant was the only thing that could keep her alive.

While the transplant saved her from cancer, she knows she could get cancer again because of it.

But Protasio said she quizzed her doctors about taking drugs that could cause cancer. And she welcomes research that might help lower the risks.

The NCI research also found a decreased risk for some cancers, such as cervical cancer. The researchers' theory is that it may reflect increased screening, and therefore earlier treatment, for this particular cancer.

The risk of breast cancer is also lower among transplant patients than in the general population. This is also probably because of better screening, said David Klassen, chairman of the medical advisory board for the National Kidney Foundation of Maryland, who has seen the study.

The study did not look at skin cancers because they weren't included in the state databases.

There is a significant increase in risk for skin cancers among organ transplant patients, said Klassen, who is also director of the kidney and pancreas transplant program at the University of Maryland Medical Center. Patients are put on a sunblock regimen and given regular screenings after a transplant, Klassen said.

Klassen said the study helped reinforce much of what was known about transplants and cancer, but could still be helpful. "It might point research to other cancer therapies."

Said Segev: "It means we have better information to care for people post-transplant."

andrea.walker@baltsun.com

twitter.com/ankwalker

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