The treatment of cholangiocarcinoma depends on the size and location of the tumor, whether the cancer has spread, and the person’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. The main treatment for bile duct cancer is surgery. Radiation therapy and chemotherapy may be used if the cancer cannot be entirely removed with surgery and in cases where the edges of the tissues removed at the operation show cancer cells (also called a positive margin). Both stage III and stage IV cancers cannot be completely removed surgically.
Radiation therapy is treatment with high-energy rays or particles that destroy cancer cells. The 2 main types of radiation therapy are external beam radiation and brachytherapy. These may be used in different settings to treat bile duct cancer:
After surgery for resectable cancers: This is known as adjuvant therapy. It is meant to kill any tiny deposits of cancer cells that remain after surgery (but are too small to see). Some doctors believe adjuvant radiation therapy is helpful, but more research is needed to confirm this.
As treatment before surgery for borderline resectable cancers: Some doctors may use radiation therapy before surgery for certain cancers that are thought to be resectable. This is done to try to shrink the cancer and make the operation easier and is known as neoadjuvant therapy. It’s not clear how helpful this is.
As part of the main therapy for some advanced cancers: Radiation therapy can also be used as a main therapy for some patients whose cancer has not spread widely throughout the body, but is not resectable. While treatment in this case does not offer a cure, it may help patients to live longer.
Radiation therapy may be given along with chemotherapy (chemo) to help it work better. This is called chemoradiation. Most often, the chemo drugs used are 5-fluorouracil (5-FU) or capecitabine (Xeloda®). The main drawback of this approach is that the side effects tend to be worse than giving radiation alone.
As palliative therapy: Radiation therapy is often used to palliate (relieve) symptoms when a patient’s cancer is too advanced to be cured. It may be used to relieve pain or other symptoms by shrinking tumors that block passageways for blood or bile, or press on nerves.
External beam radiation therapy (EBRT)
This type of radiation therapy uses x-rays from a machine outside the patient’s body to kill cancer cells. It is the most common form of radiation therapy for bile duct cancer. The treatment is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. 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. Each treatment lasts only a few minutes, but 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.
Standard (conventional) EBRT is used much less often than in the past. With newer techniques, doctors can more accurately treat bile duct cancers while reducing the radiation exposure to nearby healthy tissues. This may offer a better chance of increasing the success rate and reducing side effects.
Three-dimensional conformal radiation therapy (3D-CRT) uses special computers to precisely map the location of the tumor(s). Radiation beams are shaped and aimed at the tumor(s) from several directions, which makes it less likely to damage normal tissues. Most doctors now recommend using some form of 3D-CRT when it is available.
Intensity-modulated radiation therapy (IMRT) is an advanced form of 3D therapy. It uses a computer-driven machine that actually moves around the patient as it delivers radiation. In addition to shaping the beams and aiming them at the bile duct from several angles, the intensity (strength) of the beams can be adjusted to minimize the dose reaching the most sensitive normal tissues. This lets doctors deliver an even higher dose to the cancer areas. This procedure is available in many major hospitals and cancer centers.
Stereotactic body radiotherapy (SBRT) uses the techniques of 3D-CRT and IMRT, but gives the radiation over fewer sessions. A course of SBRT may take less than a week, while a course of radiation using these other techniques often takes place over 3 to 6 weeks.
Brachytherapy (internal radiation therapy)
This type of treatment uses small pellets of radioactive material placed next to or directly into the cancer. The radiation travels a very short distance, so it affects the cancer without causing much harm to nearby healthy body tissues. Brachytherapy is sometimes used in treating people with bile duct cancer by placing the pellets in a tube, which is inserted into the bile duct for a short time.
Palliative therapy is treatment given to help control or reduce symptoms caused by advanced cancer. It is not meant to be a curative treatment. If the cancer has spread too far to be completely removed by surgery, doctors may focus on palliative operations, palliative radiation, and other palliative therapies. Because these cancers tend to advance quickly, doctors try to use palliative therapies that are less likely to affect a person’s quality of life, when possible.
Biliary stent or biliary catheter
If cancer is blocking the bile duct, the doctor may insert a small tube (called a stent or catheter) into the duct to help keep it open. This may be done as part of a cholangiography procedure such as PTC or ERCP (see the section, “How is bile duct cancer diagnosed?”) or, in some cases, during surgery. A stent opens the duct to allow the bile to drain into the small intestine, while a catheter drains into a bag outside the body that can be emptied when needed. The stent or catheter may need to be replaced every few months if it becomes clogged and to reduce the risk of infection and gallbladder inflammation.
Another option to allow bile to reach the small intestine is to use a surgery called biliary bypass. There are several different biliary bypass operations, and the decision on which one to use is based on the location of the blockage. As mentioned in the “Surgery for bile duct cancer” section, this option is more likely to be used if a patient is already having surgery and the cancer turns out to be unresectable. While a bypass is clearly more invasive than placing a stent or catheter, it has some advantages in that the effects may last longer and infection is less likely to be a problem.
Palliative radiation therapy
Radiation therapy may be used to help relieve pain and other symptoms by killing some cancer cells that are causing blockage of the bile duct or are pressing on nerves.
Tumors in the liver that can’t be resected can sometimes be destroyed (ablated) by placing a long metal probe through the skin and into the tumor. The tip of the probe is then heated (in radiofrequency ablation) or frozen (in cryotherapy) to kill the cancer cells.
Photodynamic therapy (PDT)
For this technique, a light-activated drug is injected into a vein. A few days later, an endoscope (a long, flexible tube that can be used to look inside the body) is passed down the throat and into the bile duct. A special red light on the end of the endoscope is aimed at the tumor, causing the cells to die. The combination of PDT and stenting can help patients with bile duct cancer whose tumors aren’t resectable live longer.
To relieve pain, doctors may deaden the nerves that convey sensations of pain from the bile duct and intestinal area to the brain by injecting these nerves with alcohol. This can be done during surgery or later with the guidance of a CT.
Liver transplant: For some people with unresectable intrahepatic or perihilar bile duct cancers, removing the liver and bile ducts and then transplanting a donor liver may be an option. In some cases it might even cure the cancer.
But even for people who are eligible for a transplant, getting a new liver may not be easy. Not many centers accept patients with bile duct cancer into their transplant programs. Also, few livers are available for patients with cancer because they are generally used for more curable diseases. People needing a transplant must wait until a liver is available, which can take too long for some people with bile duct cancer. One option is having a living donor (often a close relative) give a part of their liver for transplant. This can be successful, but it carries risks for the donor.
Another option is to treat first with chemotherapy and radiation. This is followed by a transplant when a liver becomes available. This has been done as part of a clinical trial in the past, and may become a standard treatment for perihilar bile duct cancer.
Like other surgeries for bile duct cancer, a liver transplant is a major operation with potential risks (bleeding, infection, complications from anesthesia, etc.). But there are also some additional risks after this surgery.
People who get a liver transplant have to be given drugs to help suppress their immune system and prevent them from rejecting the new organ. These drugs have their own risks and side effects, especially the risk of getting serious infections. Some of the drugs used to prevent rejection can also cause high blood pressure, high cholesterol, and diabetes, can weaken the bones and kidneys, and can lead to the development of another cancer. After a liver transplant, regular blood tests are important to check for signs of rejection. Sometimes liver biopsies are also taken to see if rejection is occurring and if the anti-rejection medicines need to be changed.
Evaluation for Liver Transplantation in Adults
Martin, P., DiMartini, A., Feng, S., Brown, R. and Fallon, M. (2014), Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology, 59: 1144–1165. doi: 10.1002/hep.26972
National Leaders in Liver Transplant, Interview with Cathy and William Chapman, MD, FACS
Due to the location and sensitivity of the bile duct area, surgery for cholangiocarcinoma can be difficult. If the cancer is near the liver, part of the liver will be removed, along with the bile duct, gallbladder, and sometimes part of the pancreas and small intestine. If the cancer is near the pancreas, the surgeon may need to remove some or all of the pancreas and some small intestine. In order to maintain appropriate flow of bile, the remaining part of the bile duct has to be connected to the small intestine. About 5% to 10% of people do not survive this complicated operation; others (25% to 45%) experience serious complications, such as bleeding, infection, or leaking of bile or pancreatic juices. In some cases, surgeons cannot completely remove the tumor. Therefore, the surgeon bypasses the blocked area by connecting part of the bile duct before the blockage with a part of the small intestine beyond the blockage. The surgeon may insert a stent (a plastic or metal tube) into the bile duct to keep it open.
If the doctors think that the tumor cannot be removed by surgery, a plastic or metal stent can be passed through the blockage either during the ERCP procedure or during a procedure similar to PTC. Although these procedures do not remove the tumor, they relieve its effects and people often experience long periods of time when all of their symptoms disappear and quality of life is much better. For both these procedures, the doctor will try to insert the stent internally, so the person will not be aware of its presence. Sometimes, this is not possible, and a tube will be passed through the liver to redirect the bile externally into a bag that will need regular changing. Some doctors suggest that in these situations people receive long-term antibiotics to guard against infection.
Surgery for bile duct cancer
Surgery for bile duct cancer is a complex operation and should be done by an experienced surgeon working at a major medical center whenever possible.
There are 2 general types of surgical treatment for bile duct cancer — potentially curative surgery and palliative surgery.
Potentially curative surgery is used when imaging tests indicate a good chance that the surgeon will be able to remove all of the cancer. Doctors may use the term resectable to describe cancers they believe can be removed completely (by potentially curative surgery) and unresectable to describe those they think have spread too far or are in too difficult a place to be entirely removed by surgery. Unfortunately, only a small portion of bile duct cancers are resectable at the time they are first found.
Surgery for resectable cancers
For resectable cancers, the type of operation depends on the location of the cancer.
Intrahepatic bile duct cancer: These cancers have started in bile ducts within the liver. To treat these cancers, the surgeon cuts out the part of the liver containing the cancer. Removing part of the liver is called a partial hepatectomy. Sometimes this means that a whole lobe of the liver must be removed. This is called hepatic lobectomy. It is a complicated operation and requires an experienced team of surgeons and assistants. If the amount of liver tissue removed is not too great, the liver will function normally because its tissue has some ability to grow back.
Perihilar bile duct cancer: These cancers begin where the branches of the bile duct first leave the liver. Surgery for these cancers requires great skill, as the operation is quite extensive. Usually part of the liver is removed, along with the bile duct, gallbladder, nearby lymph nodes, and sometimes part of the pancreas and small intestine. Then the surgeon connects the remaining ducts to the small intestine. This is not an easy operation for the patient, and about 8% die from surgical complications.
Distal bile duct cancer:These cancers are further down the bile duct near the pancreas and small intestine. Along with the bile duct and nearby lymph nodes, in most cases the surgeon must remove part of the pancreas and small intestine. This operation is called a Whipple procedure and like the other operations, this is a complex procedure that requires an experienced surgical team.
Possible risks and side effects: The risks and side effects of surgery depend in large part on the extent of the operation and a person’s general health. All surgery carries some risk, including the possibility of bleeding, infections, complications from anesthesia, pneumonia, and even death in rare cases.
People will have some pain from the incision for some time after the operation, but this can usually be controlled with medicines.
Surgery for bile duct cancer is a major operation that might mean removing parts of several organs. This can significantly affect a person’s recovery and health after the surgery. Because most of the organs are involved in digestion, eating and nutrition problems are often long-term side effects of surgery for this cancer.
Surgery for unresectable cancers
Palliative surgery may be performed to relieve symptoms or treat (or even prevent) complications, such as blockage of the bile ducts. This type of surgery is performed when the tumor is too widespread to be completely removed. Palliative surgery is not expected to cure the cancer, but it can sometimes help someone feel better and sometimes can even help them live longer.
In some cases a doctor may think that a cancer is resectable based on the information available (imaging tests, laparoscopy, etc.), but once surgery is started it becomes clear that the cancer is too advanced to be removed completely. At this point the surgeon may do a biliary bypass to allow the bile to flow into the intestines to reduce symptoms such as jaundice or itching.
In this palliative procedure, the surgeon creates a bypass around the tumor blocking the bile duct by connecting part of the bile duct before the blockage with a part of the duct that lies past the blockage. Often, the gallbladder is used to provide some of the bypass.
Chemotherapy (chemo) is treatment with anti-cancer drugs that are given into a vein or by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful in some cancers that have spread to organs beyond the bile duct. Because the drugs reach all the areas of the body, this is known as a systemic treatment. Unfortunately, chemo has not been very effective against bile duct cancer, so its use has been somewhat limited. For resectable bile duct cancers (cancers that can be removed completely with surgery), chemo may be used after surgery (often along with radiation therapy) to try to lower the risk that the cancer will return. This is known as adjuvant chemo. Some doctors may use it before surgery for borderline resectable cancers to try to improve the odds that surgery will be successful. This is called neoadjuvant treatment. Chemo may also be used (sometimes with radiation therapy) for more advanced cancers. But it is not clear if chemo used in this situation helps people live longer. Doctors give chemo in cycles, with each period of treatment followed by a rest period to give the body time to recover. Chemo cycles generally last about 3 to 4 weeks. Chemo is often not recommended for patients in poor health, but advanced age by itself is not a barrier to getting chemotherapy. Hepatic artery infusion: Because of the poor response to regular (systemic) chemo, doctors have tried giving the drugs directly into the hepatic artery. This is known as hepatic artery infusion (HAI). The hepatic artery supplies blood to most bile duct tumors. The healthy liver can remove most of the remaining drug before it can reach the rest of the body. HAI may allow some people whose cancer was not removable by surgery to live longer, but more research is needed. This technique may not be useful in all cases because it often requires surgery to insert a catheter into the hepatic artery, an operation that many bile duct cancer patients might not tolerate well.
Drugs used to treat bile duct cancer
Several drugs can be used to treat bile duct cancer. In some cases, 2 or more of these drugs may be combined to try to make them more effective. The drugs that have been used most often to treat bile duct cancer include:
- 5-fluorouracil (5-FU)
- Gemcitabine (Gemzar®)
- Mitomycin C
- Doxorubicin (Adriamycin®)
- Capecitabine (Xeloda)
If you’d like more information on a drug used in your treatment or a specific drug mentioned in this section, see our Guide to Cancer Drugs, or call us with the names of the medicines you’re taking.
Possible side effects of chemotherapy
Chemo drugs work by attacking 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 chemo, which can lead to side effects. The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken. These side effects can include:
- Hair loss
- Mouth sores
- Loss of appetite
- Nausea and vomiting
- Nerve damage (neuropathy), which can lead to trouble swallowing or numbness, tingling, and even pain in the hands and feet
- Increased chance of infections (due to low white blood cell counts)
- Easy bruising or bleeding (due to low blood platelet counts)
- Fatigue (due to 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 these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about medicines to help reduce side effects, and let him or her know when you do have side effects so they can be managed effectively.
Chemoembolization is a minimally invasive treatment for liver cancer that can be used when there is too much tumor to treat with radiofrequency ablation (RFA), when the tumor is in a location that cannot be treated with RFA, or in combination with RFA or other treatments.
Chemoembolization delivers a high dose of cancer-killing drug (chemotherapy) directly to the organ while depriving the tumor of its blood supply by blocking, or embolizing, the arteries feeding the tumor. Using imaging for guidance, the interventional radiologist threads a tiny catheter up the femoral artery in the groin into the blood vessels supplying the liver tumor. The embolic agents keep the chemotherapy drug in the tumor by blocking the flow to other areas of the body. This allows for a higher dose of chemotherapy drug to be used, because less of the drug is able to circulate to the healthy cells in the body. Chemoembolization usually involves a hospital stay of two to four days. Patients typically have lower than normal energy levels for about a month afterwards.
Chemoembolization is a palliative, not a curative, treatment. It can be extremely effective in treating primary liver cancers, especially when combined with other therapies. Chemoembolization has shown promising early results with some types of metastatic tumors. Although the individual materials used in this treatment are FDA approved, the treatment itself is not approved for intra-arterial therapy of liver tumors.
Radioembolization is very similar to chemoembolization but with the use of radioactive microspheres. This therapy is used to treat both primary and metastatic liver tumors.
This treatment incorporates the radioactive isotope Yttrium-90 into the embolic spheres to deliver radiation directly to the tumor. Each sphere is about the size of five red blood cells in width. These beads are injected through a catheter from the groin into the liver artery supplying the tumor. The beads become lodged within the tumor vessels where they exert their local radiation that causes cell death. This technique allows for a higher, local dose of radiation to be used, without subjecting healthy tissue in the body to the radiation. The Yttrium-90 radiates from within and, since it is administered in the hepatic artery, it can be viewed as “internal” radiation.
Radioembolization is a palliative, not a curative, treatment-but patients benefit by extending their lives and improving their quality of life. It is a relatively new therapy that has been effective in treating primary and metastatic liver cancers. It is performed as an outpatient treatment. There are fewer side effects from this treatment compared to standard cancer treatments, with the main one being fatigue for seven to 10 days.
For inoperable liver tumors, radiofrequency ablation (RFA) offers a nonsurgical, localized treatment that kills the tumor cells with heat, while sparing the healthy liver tissue. Thus, this treatment is much easier on the patient than systemic therapy. Radiofrequency energy can be given without affecting the patient’s overall health and most people can resume their usual activities in a few days.
In this procedure, the interventional radiologist guides a small needle through the skin into the tumor. From the tip of the needle, radiofrequency energy (similar to microwaves) is transmitted to the tip of the needle, where it produces heat in the tissues. The dead tumor tissue shrinks and slowly forms a scar. The FDA has approved RFA for the treatment of liver tumors.
In a small number of cases, RFA can extend patients’ lives, but it is generally palliative. Depending on the size of the tumor, RFA can shrink or kill the tumor, extending the patient’s survival time and greatly improving their quality of life while living with cancer.
Because it is a local treatment that does not harm healthy tissue, the treatment can be repeated as often as needed to keep patients comfortable. It is a very safe procedure, with complication rates on the order of two to three percent, and has been available since the late 1990s.
By decreasing the size of a large mass, or treating new tumors in the liver as they arise, the pain and other debilitating symptoms caused by the tumors are relieved. While the tumors themselves may not be painful, when they press against nerves or interfere with vital organs, they can cause pain. RFA is effective for small to medium-sized tumors and emerging new technologies should allow the treatment of larger cancers in the future.
- Is most effective when all the cancer is localized in the liver
- Can be used to treat primary liver cancer and tumors that have metastasized (spread) from other areas in the body to the liver
- Usually does not require general anesthesia
- Is well tolerated-most patients can resume their normal routine the next day and may feel tired for a few days
- Can be repeated if necessary
- May be combined with other treatment options
- Can relieve pain and suffering for many cancer patients
Cryoablation is similar to RFA in that the energy is delivered directly into the tumor by a probe that is inserted through the skin. But rather than killing the tumor with heat, cryoablation uses an extremely cold gas to freeze it. This technique has been used for many years by surgeons in the operating room, but in the last few years, the needles have become small enough to be used by interventional radiologists through a small nick in the skin, without the need for an operation. The “ice ball” that is created around the needle grows in size and destroys the frozen tumor cells.
Control of pain is one of the most important aspects of cancer care. Pain not only affects patients’ quality of life and ability to function, it may also lower their tolerance for needed cancer treatments.
In many cancer patients, pain results from the spread of the tumor into surrounding nerves and other tissues. For example, patients with cancer of the pancreas or stomach, sometimes experience pain from the spread of the tumor into a network of nerves and blood vessels in the abdomen called the celiac plexus. To treat the pain, interventional radiologists insert catheters or needles into the affected area and administer alcohol or other agents that destroy the nerves causing the pain.
A particularly painful complication of cancer is when the disease spreads (metastasizes) to bones. In a technique called transcatheter embolization, interventional radiologists inject tiny particles, the size of grains of sand, through a catheter and into the artery that supplies blood to the tumor. The particles cause clotting that decreases the tumor’s blood supply, reducing pain and decreasing the likelihood of bone fracture.
If a cancer spreads to the blood vessels it may cause hemorrhage or bleeding. An interventional radiology technique called transcatheter embolization can be used to clot the affected blood vessels and stop the bleeding.
Treating Organ Obstruction and Infection
Cancers can obstruct the normal flow of urine or bile, causing these fluids to build up in the body. If left untreated, these conditions are not only painful but may also result in organ failure or infection. Under X-ray guidance, catheters can be inserted to drain the collection of fluids. Often, a small device called a stent is inserted into the organ to bypass the obstruction and allow fluids to drain internally.
Treating Blood Clots
One common side effect of cancer or cancer treatments is the development of blood clots, or emboli, that can be life-threatening if they travel to the brain, lungs or heart. There are two interventional radiology procedures that can reduce the risks posed by blood clots:
- Intra-arterial thrombolysis. In this technique, the interventional radiologist guides a catheter through the blood vessels and to the site of a blood clot. Clot-busting drugs are infused through the catheter to break up the clot.
- Filter placement. This technique is most often used when a blood clot is detected in the blood vessels of the leg (a condition called deep vein thrombosis). The interventional radiologist guides a small filter into the blood vessel that receives blood from the lower body (the vena cava) and carries it to the heart. If the blood clot dislodges from the vein in the leg, the filter will trap it before it can reach the heart.
*adapted from Society of Interventional Radiology
Making treatment decisions
After bile duct cancer is found and staged, your cancer care team will discuss your treatment options with you. It is important for you to take time and think about your choices. In choosing a treatment plan, there are some factors to consider:
- The location and extent of the cancer
- Whether the cancer is resectable (removable by surgery)
- The likely side effects of treatment
- Your overall health
- The chances of curing the disease, extending life, or relieving symptoms
If time permits, it is often a good idea to seek a second opinion, particularly for an uncommon cancer like bile duct cancer. A second opinion can provide more information and help you feel more confident about your chosen treatment plan.
*adapted from cancer.net