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At this time, surgery, either with resection (removal of the tumor) or a liver transplant, offers the only reasonable chance to cure liver cancer. If all known cancer in the liver is successfully removed, you will have the best outlook for survival.
Partial hepatectomy
Surgery to remove part of the liver is called partial hepatectomy. This operation is only attempted if the person is healthy enough and all of the tumor can be removed while leaving enough healthy liver behind. Unfortunately, most liver cancers cannot be completely removed. Often the cancer has spread beyond the liver, has become very large, or is in too many different parts of the liver.
More than 4 out of 5 people with liver cancer in the United States also have cirrhosis. If you have severe cirrhosis, removing even a small amount of liver tissue at the edges of your cancer might not leave enough liver behind to perform essential functions. People with cirrhosis are eligible for surgery only if the cancer is small and they still have a reasonable amount of liver function left. Doctors often assess this function by assigning a Child-Pugh score , which is a measure of cirrhosis based on certain lab tests and symptoms. Patients who fall into class A are most likely to have enough liver function to have surgery. Patients in class B are less likely to be able to have surgery. Surgery is not typically an option for patients in class C.
Possible risks and side effects: Liver resection is a major, serious operation that should only be done by skilled and experienced surgeons. Because people with liver cancer usually have damage to the other parts of their liver, surgeons have to remove enough of the liver to try to get all of the cancer, yet leave enough behind for the liver to function adequately.
A lot of blood passes through the liver at any given time, and bleeding after surgery is a major concern. On top of this, the liver normally makes substances that help the blood clot. Damage to the liver (both before the surgery and during the surgery itself) can add to potential bleeding problems.
Other possible problems are similar to those seen with other major surgeries and can include infections, complications from anesthesia, blood clots, and pneumonia.
Another concern is that because the remaining liver still has the underlying disease that led to the cancer, sometimes a new liver cancer can develop afterward.
Liver transplant
When it is available, a liver transplant may be the best option for some people with small liver cancers. At this time, liver transplants are reserved for those with small tumors (either 1 tumor smaller than 5 cm across or 2 to 3 tumors no larger than 3 cm) that have not invaded nearby blood vessels. In most cases, transplant is used for tumors that cannot be totally removed, either because of the location of the tumors or because the liver is too diseased for the patient to withstand removing part of it.
According to the Organ Procurement and Transplantation Network, about 1,100 liver transplants were done in people with liver cancer in the United States in 2009, the last year for which numbers are available. The 5-year survival rate for these patients is around 60% to 70%. Not only is the risk of a second new liver cancer significantly reduced, but the new liver will function normally.
Unfortunately, the opportunities for liver transplants are limited. Only about 6,000 livers are available for transplant each year, and most of these are used for patients with diseases other than liver cancer. Increased awareness about the importance of organ donation is an essential public health goal that could make this treatment available to more patients with liver cancer and other serious liver diseases.
Most livers for transplants come from people who have just passed away. But in recent years, a small number of patients have received part of a liver from a living donor (usually a close relative) for transplant. The liver can regenerate some of its lost function over time if part of it is removed. Still, the surgery does carry some risks for the donor. About 200 to 250 living donor transplants are done in the United States each year. Only a small number of them are for patients with liver cancer.
People needing a transplant must wait until a liver is available, which can take too long for some people with liver cancer. In many cases a person may get other treatments, such as embolization or ablation (described in following sections), while waiting for a liver transplant. Or doctors may suggest a limited resection of the cancer or other treatments first and then a transplant if the cancer comes back.
Possible risks and side effects: Like partial hepatectomy, a liver transplant is a major operation with serious potential risks (bleeding, infection, blood clots, complications from anesthesia, etc.). But there are some additional risks after this surgery.
People who get a liver transplant have to be given drugs to help suppress their immune systems to prevent their bodies from rejecting the new organ. These drugs have their own risks and side effects, especially the risk of getting serious infections. By suppressing the immune system, these drugs might also allow any remaining cancer to grow even faster than before. Some of the drugs used to prevent rejection can also cause high blood pressure, high cholesterol, diabetes, and can weaken the bones and kidneys.
After a liver transplant, regular blood tests are important to check for signs of the body rejecting the new liver. Sometimes liver biopsies are also taken to see if rejection is occurring and if changes are needed in the anti-rejection medicines.
Tumor ablation for liver cancer
Ablation refers to treatments that destroy liver tumors without removing them. These techniques are often used in patients with no more than a few small tumors but for whom surgery is not a good option (often because of poor health or reduced liver function). They are less likely to cure the cancer than surgery, but they can still be very helpful for some people. These treatments are also sometimes used to treat cancers in patients waiting for a liver transplant.
Ablation is best used for tumors no larger than about 3 cm across. For slightly larger tumors (3 to 5 cm across), it may be used along with embolization (see next section).
This type of treatment typically does not require a hospital stay.
Radiofrequency ablation (RFA)
This procedure uses high-energy radio waves for treatment. The doctor inserts a thin, needle-like probe through the skin and into the tumor, guiding it into place with ultrasound or CT scans. A high-frequency current is then passed through the tip of the probe, which heats the tumor and destroys the cancer cells. This is a common treatment method for small tumors.
Ethanol (alcohol) ablation
This is also known as percutaneous ethanol injection (PEI). In this procedure, concentrated alcohol is injected directly into the tumor to kill cancer cells. This is usually done through the skin using a needle guided by ultrasound or CT scans.
Microwave thermotherapy
In this newer procedure, microwaves are used to heat and destroy the abnormal tissue.
Cryosurgery (cryotherapy)
This procedure destroys a tumor by freezing it using a thin metal probe. The probe is guided through the skin and into the tumor by ultrasound. Then very cold gasses are passed through the probe to freeze the tumor, killing the cancer cells. This method may be used to treat larger tumors than the other ablation techniques, but it sometimes requires general anesthesia (where you are deeply asleep and not able to feel pain).
Side effects of ablation therapy
Possible side effects after ablation therapy include abdominal pain, infection in the liver, and bleeding into the chest cavity or abdomen. Serious complications are uncommon, but they are possible.
Embolization therapy for liver cancer
Embolization is the injection of substances to try to block or reduce the blood flow to cancer cells in the liver.
The liver is unusual in that it has 2 blood supplies. Most normal liver cells are fed by branches of the portal vein, whereas cancer cells in the liver are usually fed by branches of the hepatic artery. Doctors can exploit this difference to treat the cancer. Blocking the branch of the hepatic artery feeding the tumor helps kill off the cancer cells, but it leaves most of the healthy liver cells unharmed because they get their blood supply from the portal vein.
Embolization is an option for some patients with tumors that cannot be removed by surgery. It can be used for tumors that are too large to be treated with ablation (usually larger than 5 cm across). For some tumors (typically in the 3 to 5 cm range), these treatments may be used together. Embolization does reduce some of the blood supply to the normal liver tissue, so it may not be a good option for some patients whose liver has been damaged by diseases such as hepatitis or cirrhosis.
This type of treatment typically does not require a hospital stay.
Arterial embolization
Arterial embolization is also known as trans-arterial embolization (or TAE). In this procedure a catheter (a thin, flexible tube) is put into an artery through a small cut in the inner thigh and threaded up into the hepatic artery in the liver. A dye is usually injected into the bloodstream at this time to help the doctor monitor the path of the catheter via angiography, a special type of x-ray. Once the catheter is in place, small particles are injected into the artery to plug it up.
Chemoembolization
This approach, also known as trans-arterial chemoembolization (or TACE) combines embolization with chemotherapy. This is done either by coating the small particles with chemotherapy drugs before injection, or by giving chemotherapy through the catheter directly into the artery, then plugging up the artery. Studies are looking to see if chemoembolization is more effective than embolization alone.
Radioembolization
This newer technique combines embolization with radiation therapy.
In the United States, this is done by injecting small radioactive beads (called microspheres) into the hepatic artery. Brand names for these beads include TheraSphere® and SIR-Spheres®. Once infused, the beads lodge in the blood vessels near the tumor, where they give off small amounts of radiation to the tumor site for several days. The radiation travels a very short distance, so its effects are limited mainly to the tumor. Long-term data on this treatment isn't yet available, but it has been shown to help tumors shrink.
Side effects of embolization
Possible complications after embolization include abdominal pain, fever, nausea, infection in the liver, gallbladder inflammation, and blood clots in the main blood vessels of the liver. Serious complications are not common, but they are possible.
Radiation therapy for liver cancer
Radiation therapy uses high-energy rays to kill cancer cells. There are different kinds of radiation therapy.
External beam radiation therapy
This type of radiation therapy focuses radiation delivered from outside the body on the cancer. This can sometimes be used to shrink liver tumors to relieve symptoms such as pain, but it is not used as often as other local treatments such as ablation or embolization. Although liver cancer cells are sensitive to radiation, this treatment can't be used at very high doses because normal liver tissue is also easily damaged by radiation.
Before your treatments start, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Radiation therapy is much like getting an x-ray, but the radiation is stronger. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time – getting you into place for treatment – usually takes longer. Most often, radiation treatments are given 5 days a week for several weeks.
With newer radiation techniques, doctors can better target liver tumors while reducing the radiation to nearby healthy tissues. This may make it more effective and reduce side effects.
Three-dimensional conformal radiation therapy (3D-CRT): 3D-CRT uses special computers to map the location of the tumor(s) precisely. Radiation beams are then shaped and aimed at the tumor(s) from several directions, which makes it less likely to damage normal tissues.
Stereotactic body radiation therapy (SBRT): Instead of giving small doses of radiation each day for several weeks, SBRT uses very focused beams of high-dose radiation given on one or a few days. Beams are aimed at the tumor from many different angles. To target the radiation precisely, the person is put in a specially designed body frame for each treatment.
Radioembolization
As mentioned in the "Embolization therapy" section, a newer treatment technique is to inject small radioactive beads into the hepatic artery. They lodge in the liver near tumors and give off small amounts of radiation that travel only a short distance.
Side effects of radiation therapy
Side effects of external radiation therapy might include sunburn-like skin problems where the radiation enters the body, nausea, vomiting, and fatigue. Often these go away after treatment. Radiation might also make the side effects of chemotherapy worse.
Targeted therapy for liver cancer
As researchers have learned more about the changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. Targeted drugs work differently from standard chemotherapy drugs. They often have different (and less severe) side effects.
Like chemotherapy, these drugs work systemically – they enter the bloodstream and reach all areas of the body, which makes them potentially useful against cancers that have spread to distant organs. Because standard chemotherapy has not been effective in most patients with liver cancer, doctors have been looking at targeted therapies more.
Sorafenib
Sorafenib (Nexavar®) is a targeted drug that works in 2 ways. It helps block tumors from forming new blood vessels, which they need to grow. It also targets some of the proteins on cancer cells that normally help them grow.
This drug has been shown to slow the growth of advanced liver cancer and to help some patients live longer (by an average of about 3 months). Researchers are also studying its use earlier in the course of the disease, often combined with other types of treatment. It has not been studied much in people who already have poor liver function, so it's not yet clear if it is safe for these people.
Sorafenib is taken twice daily as a pill. The most common side effects of this drug include fatigue, rash, loss of appetite, diarrhea, high blood pressure, and redness, pain, swelling, or blisters on the palms of the hands or soles of the feet.
Chemotherapy for liver cancer
Chemotherapy (chemo) is treatment with drugs to destroy cancer cells. Systemic (whole body) chemotherapy uses anti-cancer drugs that are injected into a vein or given by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment potentially useful for cancers that have spread to distant organs.
Unfortunately, liver cancer resists most chemo drugs. The drugs that have been most effective in shrinking the tumors are doxorubicin (Adriamycin), 5-fluorouracil, and cisplatin. But even these drugs shrink only a small portion of tumors, and the responses often do not last long. Even with combinations of drugs, in most studies systemic chemotherapy has not helped patients live longer.
Hepatic artery infusion
Because of the poor response to systemic chemotherapy, doctors have studied putting chemo drugs directly into the hepatic artery to see if it might be more effective. This technique is known as hepatic artery infusion (HAI). The chemo goes into the liver through the hepatic artery, but the healthy liver breaks down most of the drug before it can reach the rest of the body. This gets more chemo to the tumor than systemic chemo without increasing side effects. The drugs most commonly used include floxuridine (FUDR), cisplatin, mitomycin C, and doxorubicin.
Early studies have found that HAI is often effective in shrinking tumors, but more research is still needed. This technique may not be useful in all patients because it often requires surgery to insert a catheter into the hepatic artery, an operation that many liver cancer patients may not be able to tolerate.
Side effects of chemotherapy
Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.
The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. Common side effects include:
Hair loss
Mouth sores
Loss of appetite
Nausea and vomiting
Diarrhea
Increased chance of infections (from low white blood cell counts)
Easy bruising or bleeding (from low blood platelet counts)
Fatigue (from low red blood cell counts)
These side effects are usually short-term and go away after treatment is finished. There are often ways to lessen them. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about drugs to help reduce side effects.
Along with the possible side effects in the list above, some drugs may have their own specific side effects.
You should report any side effects you notice while getting chemotherapy to your medical team so that you can be treated promptly. In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent side effects from getting worse.
Treatment of liver cancer by stage
Although the AJCC (TNM) staging system is often used to describe the spread of a liver cancer precisely, doctors use a more practical system to determine treatment options. Liver cancers are divided into 3 categories: localized resectable, localized unresectable, and advanced.
Localized resectable liver cancer (some T1 or T2, N0, M0 tumors)
If your cancer is at an early stage and the rest of your liver is healthy, surgery (partial hepatectomy) may cure you. Unfortunately, only a small number of people with liver cancer fall into this category. An important factor affecting outcome is the size of the tumor(s) and whether nearby blood vessels are affected. Larger tumors or ones that invade blood vessels are more likely to come back in the liver or spread elsewhere after surgery. The function of the rest of the liver and your general health are also important. For some people with early-stage liver cancer, a liver transplant may be another option.
Clinical trials are now looking at whether patients who have a partial hepatectomy will be helped by getting other treatments in addition to surgery. Some studies have found that using chemoembolization or other treatments along with surgery may help some patients live longer. Still, not all studies have found this, and more research is needed to know the value (if any) of adding other treatments to surgery.
Localized unresectable liver cancer (some T1 to T4, N0, M0 tumors)
Localized, unresectable cancers include cancers that haven’t yet spread, but that can’t be removed safely by partial hepatectomy for some reason:
The tumor is too large to be removed safely
The tumor is in a part of the liver that makes it hard to remove (such as very close to a large blood vessel)
There are several tumors
The rest of the liver is unhealthy (because of cirrhosis or other reasons)
These patients may be treated with a liver transplant if it is possible. Although this is a very difficult operation, it has helped many people. Transplant may cure the cancer and any underlying liver disease.
Most people must wait at least several months before a liver becomes available for transplant. In many cases a person may get other treatments, such as embolization or ablation, while waiting for a liver transplant.
If you are not eligible for a transplant, your doctor may recommend ablation of the tumor(s) using one of the methods discussed earlier. Other options may include embolization (with or without chemotherapy or radiation), targeted therapy with sorafenib, chemotherapy (either systemic or by hepatic artery infusion), and/or radiation therapy. In some cases, treatment may shrink the tumor(s) enough so that surgery (partial hepatectomy or transplant) may become possible.
Although it is unlikely that treatments other than a transplant will cure the cancer, they can reduce symptoms and may prolong life. Because these cancers can be hard to treat, clinical trials of newer treatments may offer a good option in many cases.
Advanced liver cancer (includes all N1 or M1 tumors)
Advanced cancer has spread outside of the liver (either to the lymph nodes or to other organs). Because these cancers are widespread, they cannot be treated with surgery.
If your liver is functioning well enough (Child-Pugh class A or B), the targeted therapy sorafenib may help control the growth of the cancer for a time and may help you live longer.
As with localized unresectable liver cancer, clinical trials of targeted therapies, new approaches to chemotherapy (new drugs and ways to deliver chemotherapy), new forms of radiation therapy, and other new treatments may help you. These clinical trials are also important for improving the outcome for future patients.
Treatments such as radiation might also be used to help relieve pain and other symptoms. Please be sure to discuss any symptoms you have with your cancer team, so they can treat them effectively.
Recurrent liver cancer
Cancer is called recurrent when it comes back after treatment. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Treatment of liver cancer that returns after initial therapy depends on many factors, including where it comes back, the type of initial treatment, and how well the liver is functioning. Patients with localized resectable disease that recurs in the same spot may be eligible for further surgery or local treatments like ablation or embolization. If the cancer is widespread, targeted therapy (sorafenib) or chemotherapy may be options. Patients may also wish to ask their doctor whether a clinical trial may be right for them.
Treatment may also be offered to relieve pain and other symptoms. Please be sure to discuss any symptoms you have with your cancer care team, so they may be treated effectively.
What happens after treatment for liver cancer?
For some people with liver cancer, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer growing or coming back. (When cancer comes back after treatment, it is called a recurrence.) This is a very common concern in people who have had cancer.
It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are leading full lives.
For others, the liver cancer may never go away completely. You may get regular treatment with targeted therapy, chemotherapy, or other treatments to try to help keep the cancer in check. Learning to live with cancer that does not go away can be difficult and very stressful. It has its own type of uncertainty.
Follow-up care
If you have completed treatment, your doctors will still want to watch you closely. It is very important to go to all follow-up appointments. During these visits, your doctors will ask about symptoms, do physical exams, and may order blood tests (such as alpha-fetoprotein [AFP] levels or liver function tests) or imaging tests, such as ultrasound, CT, or MRI scans.
If you have been treated with a surgical resection or a liver transplant and have no signs of cancer remaining, most doctors recommend follow-up with imaging tests and blood tests every 3 to 6 months for the first 2 years, then tests every 6 to 12 months. Follow-up is needed to check for cancer recurrence or spread, as well as possible side effects of certain treatments.
This is the time for you to ask your health care team any questions you need answered and to discuss any concerns you might have.
Almost any cancer treatment can have side effects. Some may last for a few weeks to several months, but others can last the rest of your life. Don't hesitate to tell your cancer care team about any symptoms or side effects that bother you so they can help you manage them effectively.
After your cancer treatment is finished, you will probably still need to see your cancer doctor for many years. Ask what kind of follow-up schedule you can expect.
It is important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.
What`s new in liver cancer research and treatment?
Because there are only a few effective ways to prevent or treat liver cancer at this time, there is always a great deal of research going on in the area of liver cancer. Scientists are looking for causes and ways to prevent liver cancer, and doctors are working to improve treatments.
Prevention
The most effective way to reduce the worldwide burden of liver cancer is to prevent it from happening in the first place. Some scientists believe that vaccinations and improved treatments for hepatitis could prevent about half of liver cancer cases worldwide. Researchers are studying ways to prevent or treat hepatitis infections before they cause liver cancers. Research into developing a vaccine to prevent hepatitis C is ongoing. Progress is also being made in treating chronic hepatitis.
Screening
Several new blood tests are being studied to see if they can pick up liver cancer earlier than using AFP and ultrasound.
Surgery
Newer techniques are being developed to make both partial hepatectomy and liver transplants safer and more effective.
Adding other treatments to surgery
An active area of research uses adjuvant therapies – treatments given right after surgery – to try to reduce the chances that the cancer will return. Most of the studies so far using chemotherapy or chemoembolization after surgery have not shown that they help people live longer. But newer drugs, such as the targeted drug sorafenib (Nexavar), may prove to be more effective. Some promising results have also been seen with radioembolization, but these need to be confirmed in larger studies.
Doctors are also studying ways to make more liver cancers resectable by trying to shrink them before surgery. Studies are now looking at different types of neoadjuvant therapies (therapies given before surgery), including targeted therapy, chemotherapy, ablation, embolization, and radiation therapy. Early results have been promising but have only looked at small numbers of patients.
Laparoscopic surgery
In laparoscopic surgery, several small incisions are made in the abdomen, and special long, thin surgical instruments are inserted to view and cut out the diseased portion of the liver. It does not require a large incision in the abdomen, which means there is less blood loss, less pain after surgery, and a quicker recovery.
At this time, laparoscopic surgery is still considered experimental for liver cancer. It is being studied mainly in patients with small tumors in certain parts of the liver that can be easily reached through the laparoscope.
Determining recurrence risk after surgery
After a partial hepatectomy, one of the biggest concerns is that the cancer might come back (recur). Knowing someone's risk for recurrence after surgery might give doctors a better idea of how best to follow up with them, and may someday help determine who needs additional treatment to lower this risk.
Researchers may have found a way to do this by testing the cells in the surgery sample. In a recent study, they looked at the pattern of genes in liver cells near the tumor (not the tumor cells themselves) and were able to predict which patients were at higher risk for recurrence. This is an early finding that will need to be confirmed in other studies before it is widely used.
Liver transplant
Only a small portion of patients with liver cancer may be candidates for a liver transplant at this time because of the strict criteria they need to meet (based mainly on the size and number of tumors). Some doctors are now looking to see if these criteria can be expanded, so that people who are otherwise healthy but have slightly larger tumors might also be eligible.
A major problem for patients needing a transplant is the lack of an available liver. Even for people who are eligible, there can be a long wait before a liver becomes available. Doctors are looking at using other treatments, such as ablation, to help keep the cancer in check until a new liver is available.
Radiation therapy
The main problem with using radiation therapy against liver cancer is that it also damages healthy liver tissue. Researchers are now working on ways to focus radiation therapy more narrowly on the cancer, sparing the nearby normal liver tissue. Several new approaches to radiation therapy are being tried, including stereotactic body radiation therapy. Radiosensitizers (drugs that make cancers more vulnerable to radiation) are also being studied.
Targeted therapy
New drugs are being developed that work differently from standard chemotherapy drugs. These newer drugs target specific parts of cancer cells or their surrounding environments.
Tumor blood vessels are the target of several newer drugs. Liver tumors need new blood vessels to grow beyond a certain size. The drug sorafenib (Nexavar®), which is already used for some liver cancers that can't be removed surgically, works in part by hindering new blood vessel growth. This drug is now being studied for use earlier in the course of the disease, such as after surgery or trans-arterial chemoembolization (TACE). Researchers are also studying whether combining it with chemotherapy or with other targeted drugs, such as erlotinib (Tarceva®), may make it more effective.
Brivanib is another targeted drug that works, at least in part, by slowing the growth of tumor blood vessels. It has shown promise in early studies and is now being tested in larger clinical trials.
Bevacizumab (Avastin®) also works to block new blood vessel growth. It has shown promising results against liver cancer both alone and in combination with the drug erlotinib in early studies, although more research is needed.
Other new drugs have different targets. For example, the drug erlotinib, which targets a protein called EGFR on cancer cells, has shown some benefit in people with advanced liver cancer in early studies. Several other targeted drugs are now being studied as well.
Chemotherapy
New forms of systemic and regional chemotherapy combined with other treatments are being tested in clinical trials. A small number of tumors respond to chemotherapy, although it has not yet been shown to prolong survival.
Newer chemotherapy drugs, such as oxaliplatin, capecitabine, gemcitabine, and docetaxel, are being tested against liver cancer in clinical trials. The drug oxaliplatin has shown promising results in early studies when given in combination with doxorubicin and also when given with gemcitabine and the targeted therapy drug cetuximab (Erbitux®).
Virus therapy
A newer approach to treatment is the use of a virus known as JX-594. This is the same virus that was used to make the smallpox vaccine, but it has been altered in the lab so that it mainly infects cancer cells and not normal cells. It is injected into the blood and enters the cancer cells, where it causes them to die or to make proteins that result in them being attacked by the body’s immune system.
Early results against advanced liver cancer have been promising, even in patients who have already had other treatments, and larger studies of this treatment are now being done.
