Treatment & Management of Uterine Cancer

Overview of the treatment of uterine cancer; surgery, radiation therapy, and systemic treatments.

Treatment & Management of Uterine Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 10/2018

Treatment for uterine cancer is tailored to each individual and may include surgery, radiation, and chemotherapy or precision cancer medicines. The specific treatment can depend on the stage and genomic profile of the cancer. Optimal treatment of patients with uterine cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving gynecologic oncologists and radiation oncologists.

Surgery: Surgery for uterine cancer is typically performed in order to remove the cancer and learn additional information about the stage or extent of spread of the cancer. A surgeon who specializes in treatment of disorders of the female reproductive tract is known as a gynecologist. Gynecologic oncologists are gynecologists who have special training in treatment of cancers of the female reproductive tract. Gynecologic oncologists have developed expertise in performing surgical treatment of uterine cancer.

The standard surgery for treatment of uterine cancers is a total abdominal hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries). In addition to removing the uterus and ovaries, the surgeon will often sample or remove the pelvic and para-aortic lymph nodes to determine if cancer has spread. Patients with early stage uterine cancer are curable with surgical removal of the cancer.[1],[2]

Radiation Therapy: Radiation therapy, or radiotherapy, is the treatment of cancer using ionizing radiation. This radiation can be delivered externally or internally. Radiation therapy, unlike chemotherapy, is considered a local treatment. Cancer cells can only be killed where the radiation is delivered to the body. If cancer exists outside the radiation field, the cancer cells are not destroyed by the radiation. Radiation therapy is the most commonly used as adjuvant therapy for early-stage uterine cancers. The objective of adjuvant radiation therapy is to kill cancer cells that were not removed by surgery for a maximum probability of a cure. Women who are candidates for adjuvant radiation therapy may be treated with external beam radiation therapy to the pelvis and/or vaginal brachytherapy.[1]

Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy

Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Some patients with early stage cancers already have small amounts of cancer that have spread outside uterus. These cancer cells cannot be treated with surgery or radiation and require systemic treatment to decrease the chance of cancer recurrence. More advanced cancers that cannot be treated with surgery and radiation can only be treated with systemic therapy.

Systemic therapies commonly used in the treatment of cancer include:

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. The drugs are usually given in cycles so that a recovery period follows every treatment period.

Most chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell. Therefore, chemotherapy often affects the body’s normal tissues and organs, which can result in complications or side effects. In order to more specifically target the cancer and avoid unwanted side effects researchers are increasingly developing precision cancer medicines.[3]

Precision Cancer Medicines

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision medicines are just beginning to undergo evaluation in uterine cancer and patients should ask their doctor about whether testing is appropriate.

Treatment of Uterine Cancer by Stage

In order to learn more about the most recent information available concerning the treatment of uterine cancer, click on the appropriate stage.

Stage I: Cancer does not spread outside the body of the uterus.

Stage II: Cancer involves the body of the uterus and the cervix.

Stage III: Cancer extends outside the uterus, but is confined to the pelvis.

Stage IV: Cancer involves the bladder or bowel or distant sites.

Recurrent: Cancer has returned after initial treatment.

Surgery for Uterine Cancer

Surgery for uterine cancer is performed in order to remove the cancer and learn additional information about the stage or extent of spread of the cancer. A surgeon who specializes in treatment of disorders of the female reproductive tract is known as a gynecologist. Gynecologic oncologists are gynecologists who have special training in treatment of cancers of the female reproductive tract. Gynecologic oncologists have developed expertise in performing surgical treatment of uterine cancer.

The standard surgery for treatment of uterine cancers is a total abdominal hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries). In addition to removing the uterus and ovaries, the surgeon will often sample or remove the pelvic and para-aortic lymph nodes to determine if cancer has spread.

Dilation and Curettage

Dilation and curettage (D&C) is a common diagnostic procedure used by gynecologists to obtain tissue from the wall of the uterus. During a D&C, the vagina is washed with an antiseptic and a local anesthetic is injected into or near the cervix. Injectable painkillers or general anesthesia can also be used. The opening of the cervix is gradually stretched. One after the other, a series of increasingly thick rods (dilators) are inserted into the cervical opening. The thickest dilator may be the width of a fountain pen. As an alternative, absorbent dilators can be used to stretch the cervical opening. These dilators absorb fluids from the cervical area and stretch the opening of the cervix as the dilators expand. Scraping (curetting) the lining of the uterus yields tissue, which can then be looked at under the microscope to determine if cancer is present. Rarely, if ever, is curettage used for the treatment of uterine cancer since only a superficial layer of the uterus is removed.

Hysterectomy and Pelvic Lymph Node Dissection

The standard treatment of stages I – III uterine cancer is a total abdominal hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries) with or without removal of the pelvic and para-aortic lymph nodes. When the uterus is surgically removed, the cut ends of the vagina are surgically sewn together forming what is termed a “vaginal cuff”. The vaginal cuff is a site of local cancer recurrence following surgery alone.

A hysterectomy is most effective if the exploration during surgery shows the cancer has not spread beyond the uterus. Some patients, however, will have cancer that has spread outside the uterus into the lymph nodes in the pelvis. Before the hysterectomy is done, the doctor will sometimes perform a pelvic lymph node dissection. During a pelvic lymph node dissection, the surgeon removes lymph nodes to determine whether they contain cancer. If the lymph nodes contain cancer, the surgeon may not proceed with the hysterectomy. Another form of treatment, usually radiation therapy and chemotherapy, is generally recommended.

Despite the surgical removal of the uterine cancer, some patients may experience recurrence of their cancer. It is important to realize that some patients with uterine cancer already have small amounts of cancer that have spread outside the uterus and were not removed by surgery. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the cervix are referred to as micrometastases. The presence of these microscopic areas of cancer causes recurrence following the initial treatment. External beam radiation therapy with or without implant radiation and chemotherapy are often recommended to cleanse the body of micrometastases in order to improve the cure rate achieved with surgical removal of the cancer.

“Debulking” Surgery for Inoperable Cancer of the Uterus

When the cancer cannot be completely removed, an appropriate question to ask is whether surgical removal of as much cancer as possible is beneficial. This is referred to as a “debulking surgery”, and is often performed so that radiation therapy and/or chemotherapy will have fewer cancer cells to kill. This, however, is major surgery and has many potential complications. The value of debulking surgery has not been clearly demonstrated in controlled clinical studies. However, researchers have evaluated the outcomes of women with advanced uterine cancer who underwent debulking surgery. Patients with less than 2 centimeters of cancer remaining after debulking surgery were compared to patients who had more than 2 centimeters of cancer remaining and patients who did not undergo debulking surgery. The average survival for optimal surgical debulking (less than 2 cm remaining) was 32 months, compared to 12 and 13 months for women with inadequate or no debulking. Thus, there may be a role for surgically removing as much cancer as possible in women with widespread uterine cancer.

Role of Para-aortic Lymphadenectomy

When uterine cancer spreads, it leaves the uterus and travels into lymph nodes in the pelvis near the uterus. From the pelvic lymph nodes it spreads to lymph nodes around the main artery from the heart called the aorta. These lymph nodes are called para-aortic lymph nodes.

During surgery, the pelvic lymph nodes are often removed, but the value of removing the para-aortic lymph nodes is less clear. If removal of para-aortic lymph nodes improved the chance of cure and/or prolonged survival, it would be beneficial. On the other hand, if para-aortic lymph node removal merely increases the side effects of surgery, it would be unadvisable.

Surgeons have attempted to evaluate whether para-aortic lymph node removal is beneficial. In a clinical study of 137 women at high-risk for para-aortic lymph node involvement, the cancer recurrence rate was 38% and the 5-year survival rate was 71% for those who did not have lymph nodes removed, compared to a recurrence rate of 23% and survival of 85% for those who did have lymph nodes removed. These doctors suggest that patients at high risk for lymph node spread should consider surgical removal of the para-aortic lymph nodes as well as the pelvic lymph nodes.

Side Effects of Surgery

Women undergoing a hysterectomy may experience lower abdominal incisional pain, bleeding or infection after the operation because it may reduce the risk of cancer recurrence and prolong survival. Difficulty with urination or problems with bladder control can also occur in women treated with surgery. Less commonly, injury to the rectum or tubes which drain the kidneys (ureters) or bladder occurs. This may be in the form of a “fistula” or abnormal connection to the vagina. For women of childbearing age, the effects of surgery are drastic, since the uterus and both ovaries are removed. Obviously, such surgery precludes childbirth. In addition, the removal of both ovaries precipitates menopause and the need for consideration of hormone replacement.

Surgical removal of the pelvic or para-aortic lymph nodes may cause lower-body lymphedema in some women.[1] Lymphedema is the buildup of lymph fluid in the tissues just under the skin, resulting in swelling, tightness and discomfort in the affected part of the body. Damage to or blockage of the lymph system is the cause of lymphedema.

Radiation Therapy for Uterine Cancer

The objective of radiation therapy is to kill uterine cancer cells for a maximum probability of cure or palliation with a minimum of side effects. Radiation therapy can be used to prevent local cancer recurrences after surgery (adjuvant therapy) or for the treatment of recurrent cancer. Radiation is generally given in the form of high-energy beams that deposit the radiation dose into the body where the risk of cancer cells is greatest. Radiation therapy, unlike chemotherapy, is considered a local treatment. Cancer cells can only be killed where the actual radiation is delivered to the body. If cancer exists outside the radiation field, the cancer cells are not destroyed by the radiation. Therefore, radiation therapy is typically used for early stage cancers confined to a single location (field) in the body.

Radiation can also be directly placed in the area of the cancer (brachytherapy) or in the area where unseen cancer is suspected. For uterine cancer, this is the “vaginal cuff” region where the incision was made when the uterus was removed. Brachytherapy does not penetrate very deep and external beam radiation therapy is often combined with brachytherapy for treatment of uterine cancer.

Modern radiation therapy for uterine cancers is given via machines called linear accelerators, which produce high-energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas where the cancer resides. These modern machines and other state-of-the-art techniques have enabled radiation oncologists to significantly reduce side-effects while improving the ability to deliver a maximum radiation dose to cancer-containing areas and minimizing the radiation dose to normal tissue.

Simulation

After an initial consultation with a radiation oncologist, the next session is usually a planning session, which is called a simulation. During this session, the radiation treatment fields and most of the treatment planning are determined. Of all the visits to the radiation oncology facility, the simulation session may actually take the most time. During simulation, patients lie on a table somewhat similar to that used for a CT scan. The table can be raised and lowered and rotated around a central axis. The “simulator” machine is a machine whose dimensions and movements closely match that of an actual linear accelerator. Rather than delivering radiation treatment, the simulator lets the radiation oncologist and technologists see the area to be treated. The simulation is usually guided by fluoroscopy, so that a patient’s internal anatomy can be observed (mainly the skeleton, but if contrast material is given, the kidneys, bowels, bladder or esophagus can be visualized as well). The room is periodically darkened while the treatment fields are being set and temporary marks may be made on the patient’s skin with magic markers. The radiation oncologist is aided by one or more radiation technologists and often a dosimetrist, who performs calculations necessary in the treatment planning.

The simulation may last anywhere from 15 minutes to an hour or more, depending on the complexity of what is being planned. Once the aspects of the treatment fields are satisfactorily set, x-rays representing the treatment fields are taken. In most centers, the patient is given multiple “tattoos” which mark the treatment fields, and replace the marks previously made with magic markers. These tattoos are not elaborate and consist of no more than pinpricks followed by ink, appearing like a small freckle. Tattoos enable the radiation technologists to set up the treatment fields each day with precision, while allowing the patient to wash and bathe without worrying about obscuring the treatment fields.

Radiation treatment is usually given in another room separate from the simulation room. The treatment plans and treatment fields resulting from the simulation session are transferred over to the treatment room, which contains a linear accelerator focused on a patient table similar to the one in the simulation room. The treatment plan is verified and treatment started only after the radiation oncologist and technologists have rechecked the treatment field and calculations and are thoroughly satisfied with the “setup”.

Treatment Schedules

A typical course of radiation for uterine cancer would entail daily radiation treatments, Monday through Friday, for 3 to 5 weeks. The actual treatment with radiation generally last no more than a few minutes, during which time the patient is unlikely to feel any discomfort. Anesthesia is not needed for radiation treatments and patients generally have few restrictions on activities during radiation therapy. Many patients continue to work during the weeks of treatment. Patients are encouraged, however, to carefully gauge how they feel and to not overexert themselves.

Side Effects and Complications

The vast majority of patients are able to complete radiation therapy for uterine cancer without significant difficulty. Side effects and potential complications of radiation therapy are infrequent and when they do occur are typically limited to the areas that are receiving treatment with radiation. The chance of a patient experiencing side effects, however, is highly variable. A dose that causes some discomfort in one patient may cause no side effects in other patients. If side effects occur, the patient should inform the technologists and radiation oncologist because treatment is almost always available and effective.

Radiation therapy to the abdominal/pelvic area may cause diarrhea, abdominal cramping or increased frequency of bowel movements or urination. These symptoms are usually temporary and resolve once the radiation is completed. Occasionally abdominal cramping may be accompanied by nausea.

Blood counts can be affected by radiation therapy. In particular, the white blood cell and platelet counts may be decreased. This is dependent on how much bone marrow is in the treatment field and whether the patient has previously received or is receiving chemotherapy. These changes in cell counts are usually insignificant and resolve once the radiation is completed. However, many radiation therapy institutions make it a policy to check the blood counts at least once during the radiation treatments. It is not unusual for some patients to note changes in sleep or rest patterns during the time they are receiving radiation therapy and some patients will describe a sense of tiredness and fatigue.

Late complications are infrequent following radiation treatment of uterine cancer. Potential complications do include bowel obstruction, ulcers or cancers caused by the radiation. Radiation to the pelvis also increases the risk of lower-body lymphedema. Lymphedema is the buildup of lymph fluid in the tissues just under the skin, resulting in swelling, tightness and discomfort in the affected part of the body. The probabilities of these late complications are affected by previous extensive abdominal or pelvic surgery, radiation therapy and/or concurrent chemotherapy.

Adjuvant Radiation Therapy

The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy, hormonal therapy and/or biologic therapy. The goal of adjuvant radiation therapy is to eradicate any remaining cancer cells after surgery. Adjuvant radiation therapy may consist of brachytherapy and/or external beam radiation.

Stage I Uterine Cancer: Although it is still being evaluated in clinical trials, many patients with stage IB and IC uterine cancer are often treated with adjuvant radiation therapy. When the uterus is surgically removed, the cut ends of the vagina are surgically sewn together forming a “vaginal cuff”. The vaginal cuff is a common site of local cancer recurrence following treatment with surgery alone. Women with stage I uterine cancer who receive treatment with surgery and postoperative radiation therapy have a 5-year survival of 80-90% and a local cancer recurrence rate of only 4-8%.

A large clinical trial that involved 715 women with stage I uterine cancer compared treatment with surgery alone or treatment with surgery followed by adjuvant external beam radiation therapy. These women had deep invasion of the muscle wall of the uterus and/or had high-grade (more aggressive) types of cancer. The cancer recurrence rates were 4% for patients treated with surgery and radiation and 14% for patients treated with surgery alone. Survival rates, however, were 81% for treatment with surgery and adjuvant radiation therapy and 85% for surgery alone. Although patients treated with surgery and radiation experienced fewer cancer recurrences, patients treated with surgery alone survived longer. This is because there were more side effects in women treated with radiation therapy. The doctors concluded that postoperative radiation therapy reduced local recurrences of cancer following surgery for stage I uterine cancer, but did not improve survival.

Brachytherapy treatment involves the placement of a radioactive isotope into the vagina and may have fewer side effects than external beam radiation. Brachytherapy delivers radiation therapy at a very high dose rate in 3 weekly treatments to the “vaginal cuff” region. Brachytherapy without external beam radiation therapy has been used to prevent local recurrences after surgery. In a clinical trial that involved 102 women with stage IB and IC uterine cancer who were treated with brachytherapy following surgery, cancer recurrences occurred in 7% of women, 4% of which were local recurrences. Of the 3 local recurrences, only one occurred in the vaginal cuff. The survival at 5 years was 84%. Brachytherapy alone appeared very effective for preventing local cancer recurrences without the major side effects associated with external beam radiation.

Researchers in Florida have also evaluated outcomes of 396 women with stage I uterine cancer treated with hysterectomy, lymph node dissection and brachytherapy. Following treatment, 5-year survival was 100% for patients with stage IA cancer, 97% for patients with stage IB cancer and 93% for patients with stage IC cancer. All cancer recurrences occurred at distant sites that would not have been treated in an external beam radiation field. These studies suggest that brachytherapy alone is as effective for the treatment of stage I uterine cancer as external beam radiation therapy.

However, since these clinical trials did not directly compare brachytherapy to brachytherapy plus hysterectomy, it remains unknown whether hysterectomy plus brachytherapy definitely improves survival compared to surgery alone. This is because treatment of a local cancer recurrence in patients initially treated with surgery can be accomplished with additional surgery and/or radiation. A strategy utilizing initial treatment with surgery alone followed by additional surgery or radiation therapy only for the 5-20% of patients who experience a local cancer recurrence would spare the majority of women with stage IB and IC uterine cancer from radiation treatment. For patients who do not receive radiation therapy, frequent examinations are necessary because 5-20% of patients will experience a local cancer recurrence following treatment with surgery alone. It is important to detect recurrences early.

Stage II Uterine Cancer: Treatment of stage II uterine cancer with surgery followed by adjuvant brachytherapy and external beam radiation therapy has been reported to cure 60-80% of patients. Post-operative radiation therapy consists of external beam radiation to the pelvis, brachytherapy or both external beam radiation therapy and brachytherapy.

Despite adjuvant radiation therapy, 20-40% of patients will experience a cancer recurrence. Recurrences occur outside the pelvis in 25% of women, primarily those with cancer deep in the uterus and those with less differentiated cancers under the microscope. Further treatment with systemic hormonal and/or chemotherapy, in addition to radiation therapy, may be required to prevent recurrences in the 25% who fail treatment outside the pelvis.

Stage III Uterine Cancer: Patients with stage III uterine cancer who have complete surgical removal of all cancer are candidates for adjuvant radiation therapy. The objective of adjuvant radiation therapy is to kill cancer cells that persist after surgery for a maximum probability of cure with a minimum of side effects. Treatment of stage III uterine cancer with surgery followed by adjuvant brachytherapy and/ or external beam radiation therapy has been reported to cure approximately 50% of patients.

Despite adjuvant radiation therapy, many patients will experience a cancer recurrence. Further treatment with systemic hormonal and/or chemotherapy, instead of or in addition to radiation therapy, may be required to further decrease the risk of cancer recurrence in patients with stage III cancer.

Radiation Therapy for Stage IV Uterine Cancer: For bulky pelvic disease, radiation therapy consisting of a combination of brachytherapy and external-beam radiation therapy is used. Radiation therapy provides significant palliation for patients with inoperable uterine cancer.

Women with Early Stage Cancer who Fail Treatment with Surgery Alone

Women who initially had stage I or IIB cancer and recur after treatment with surgery alone are frequently cured with further surgery and the addition of radiation therapy. Radiation therapy is usually given as brachytherapy and external-beam radiation therapy. This therapy is often successful, since stage I and IIB patients treated initially with surgery alone have frequent follow-up examinations with detection of a recurrence early when it is curable. For patients with bulky pelvic disease, radiation therapy consisting of a combination of brachytherapy and external-beam radiation therapy is also used. Radiation therapy can decrease symptoms and improve survival for patients with inoperable uterine cancer.

Women who Fail Surgery and Radiation Therapy

Further radiation therapy in women who have failed initial radiation is usually not possible. However, some women will fail treatment that only included brachytherapy and these women could be treated with external-beam radiation therapy if they develop a recurrence in the pelvis away from the site of isotope placement.

Radiation Treatment of Metastatic Uterine Cancer

Metastatic uterine cancers, especially large cancers, may respond poorly to chemotherapy. In these instances, radiation therapy may also be needed to have the best chance of cure. In other instances, cancer may have invaded critical areas such as the spinal cord, resulting in symptoms such as pain or weakness. Radiation therapy in these instances may also be necessary, and is usually effective in “palliating” the symptoms. In some patients, the cancer may have spread widely and have gone into areas that are difficult to treat with chemotherapy, such as the brain. Brain metastases are also often treated with radiation therapy. Side effects resulting from radiation therapy for each of these situations are usually limited to the area being treated. The radiation oncologist usually selects a dose that is expected to be effective but is also under the tolerance of the nearby normal tissues and organs, also taking into account whether chemotherapy is being administered.

References:

[1] Lu KH. Management of early-stage endometrial cancer. Seminars in Oncology. 2009;36:137-144.

[2] Frederick PJ, Straughn JM. The role of comprehensive surgical staging in patients with endometrial cancer. Cancer Control. 2009;16:23-29.

[3] Miller DS, Fleming G, Randall ME. Chemo- and radiotherapy in adjuvant management of optimally debulked endometrial cancer. Journal of the National Comprehensive Cancer Network. 2009;7:535-541.

[4] Humphrey MM, Apte SM. The use of minimally invasive surgery for endometrial cancer. Cancer Control. 2009;16:30-37.

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