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.
Delivery of Radiation Therapy for Uterine Cancers
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.
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”.
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.
Strategies to Improve Treatment
The progress that has been made in the treatment of uterine cancer with radiation therapy has resulted from the development of improved radiation delivery techniques and doctor and patient participation in clinical studies. Future progress in the treatment of cancer of the uterus will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of recurrent uterine cancer.
Improved delivery of radiation: Radiation oncologists continue to evaluate methods of delivering radiation therapy, including conformal radiation, where sophisticated imaging techniques are used to define the cancer in three dimensions. Conformal radiation allows delivery of more radiation to the cancer while sparing normal tissues. Radiation oncologists are also evaluating placement of different isotopes in attempts to improve brachytherapy. Radioactive isotopes are also being linked to monoclonal antibodies, which may assist in localizing radiation specifically to the area of cancer.