Cervical cancer diagnosed as stage IV disease is commonly detected from an abnormal pelvic examination or symptoms produced by the patient’s cancer. Following a staging evaluation of cervical cancer, a stage IV cancer is said to exist if the cancer has extended beyond the cervix into adjacent organs, such as the rectum or bladder (stage IVA), or the cancer has spread to distant locations in the body which may include the bones, lungs or liver (stage IVB). Cervical cancer diagnosed in this stage is often difficult to treat, and a small minority of patients are cured of disease.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of stage IV cervical cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed by following the cancer news in order to learn about new treatments and the results of clinical trials.
Patients diagnosed with stage IV cervical cancer can be broadly divided into two groups. Patients with disease that is locally confined, but involves adjacent organs in the pelvis, such as the rectum and bladder, have localized stage IVA cervical cancer. Other patients have disease that has spread to distant organs, most commonly the bones, lungs or liver, and have metastatic stage IVB cervical cancer. Management of patients with metastatic stage IVB disease is aimed at control of symptoms and pain. After undergoing treatment for cervical cancer, your doctor will continue to follow you to check to see that the cancer has not returned or is not progressing.
Treatment of Localized Stage IVA Cervical Cancer
Stage IVA cervical cancer is currently best managed by a combination of radiation therapy and chemotherapy. Radiation therapy is treatment with high energy x-rays that have the ability to kill cancer cells. Radiation therapy can be administered by a machine that aims x-rays at the body (external beam radiation) or by placing small capsules of radioactive material directly near the cervix (internal or implant radiation). Most patients will receive both kinds of radiation therapy during their course of treatment. External beam radiation therapy for cervical cancer is administered on an outpatient basis for approximately 4 to 6 weeks.
During or immediately following the external beam portion of radiation therapy, patients may also undergo an implant radiation procedure. Placing the radiation within the cervix allows a high dose of radiation to be delivered to the cancer while reducing the radiation to the surrounding normal tissues and organs. During a procedure in the operating room, a small device is placed into the cervix and vagina and later is “loaded” with radioactive material. The radioactive material is left in place while the patient stays in the hospital for 1-3 days. This process may be performed once or twice during the course of treatment.
Prior to the 1990s, the standard treatment of locally advanced cervical cancer had utilized external beam and internal radiation therapy and no significant progress in the treatment of cervical cancer occurred for many years. More recently, however, the addition of chemotherapy (anti-cancer drugs) has improved long-term outcomes in patients with this disease.
Chemotherapy, such as Platinol®, 5-fluorouracil and other drugs, has the ability to kill cancer cells and make radiation therapy more effective at killing cancer cells. The strategy of administering chemotherapy concurrently with radiation treatment is appealing because chemotherapy and radiation therapy may act together to increase the killing of cancer cells. Chemotherapy may also destroy cells independently of radiation therapy. Several clinical studies performed in patients with locally advanced cervical cancer utilizing concurrent chemotherapy and radiation therapy have suggested that this strategy may improve remission rates and prolong survival. In order to definitively determine whether radiation therapy administered with concurrent chemotherapy is superior to radiation therapy alone, several clinical studies were designed to directly compare the two treatments in patients with locally advanced cervical cancer.
One recent pivotal clinical trial conducted by various oncology groups in the United States has shown that radiation therapy combined with chemotherapy for locally advanced cervical cancer is superior to treatment with radiation therapy alone. In this study, 403 patients were treated with radiation therapy alone or radiation therapy plus concomitant 5-fluorouracil and Platinol® chemotherapy. Patients with stage III or IVA cervical cancer experienced a 5-year survival rate of 63% compared to 57% for patients treated with radiation therapy alone. The chance of cancer recurrence was 42% for patients treated with chemotherapy and radiation therapy compared to 62% for those treated with radiation therapy alone. Concurrent chemotherapy and radiation therapy were well tolerated except for minor gastrointestinal and hematologic side effects, which were reversible.
In summary, the combination Platinol® chemotherapy administered concurrently with radiation produces superior overall survival and a decreased risk of cancer recurrence compared to treatment with radiation therapy alone. Continued research is ongoing to determine whether additional chemotherapy drugs or doses of radiation may improve the outcome of patients with locally advanced cervical cancer. At least four other clinical studies have confirmed that treatment of locally advanced cervical cancer with concurrent Platinol®-based chemotherapy and radiation therapy is superior to radiation therapy alone.
Even with combination chemotherapy and radiation treatment, approximately 20-40% of patients with stage IV cervical cancer experience recurrence of their cancer. In some patients, cancer cells may have survived near the cancer despite the radiation therapy. Other patients with stage IV disease already have small amounts of cancer that have spread outside the cervix and were not treated by the chemotherapy. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the cervix gland are referred to as micrometastases. The presence of these microscopic areas of cancer or surviving cancer cells can cause the relapses that follow treatment.
Treatment of Metastatic Stage IVB Cervical Cancer
Cervical cancer that has spread to distant organs and bones is difficult to treat. Historically, patients with metastatic cervical cancer have been considered incurable and rarely survive more than a year or two. Some patients are offered treatment with chemotherapy for the purpose of prolonging their duration of survival and alleviating symptoms from progressive cancer. Other patients are managed with efforts to reduce pain or bleeding, including local radiation therapy to affected parts of the body.
There is no good single chemotherapy approach that can improve the length of survival in patients with metastatic cervical cancer. Treatment with Platinol® can produce shrinkage in 15-25% of patients with metastatic cervical cancer. Many clinical trials have combined Platinol® with other chemotherapy drugs in hopes of improving cancer shrinkage and survival. Although these combination regimens can have more side effects, length of survival has not been improved over Platinol® alone. Unfortunately, these chemotherapies typically work for only a few months before the cervical cancer begins to grow again. Most patients still succumb to cancer and better treatment strategies are clearly needed.
Strategies to Improve Treatment
The progress that has been made in the treatment of cervical cancer has resulted from development of better treatments in patients with more advanced stages of cancer and participation in clinical trials. While some progress has been made in the treatment of metastatic cervical cancer, the majority of patients still succumb to cancer and better treatment strategies are clearly needed. Future progress in the treatment of cervical cancer will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of cervical cancer.
Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.
New Chemotherapy Regimens: Several newer chemotherapeutic drugs have demonstrated ability to kill cervical cancer cells in patients with advanced cancer. One area of active investigation is the development and exploration of single or multi-agent chemotherapy regimens as a treatment approach for patients with widespread cervical cancer. In particular, drugs such as paclitaxel, ifosfamide, Taxotere®, Navelbine® and Camptosar® appear to have promising activity against cervical cancer cells and are being tested alone or in combination with radiation and other anticancer agents in clinical trials.
Newer Radiation Techniques: External beam radiation therapy can be delivered more precisely to the cervix by using a special CT scan and targeting computer. This capability is known as three-dimensional conformal radiation therapy, or 3D-CRT. The use of 3D-CRT appears to reduce the chance of injury to nearby body structures, such as the bladder or rectum.
Biological Therapy: Biologic therapies are naturally occurring or synthesized substances that direct, facilitate or enhance the body’s normal immune defenses. The goal of biologic therapy is to have the patient’s own immune defenses attack and destroy the cancer cells. Biologic therapies include interferons, interleukins, monoclonal antibodies and vaccines. In an attempt to improve survival rates, these and other agents are being tested alone or in combination with chemotherapy in clinical trials.
Phase I Trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent cancers in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the safety and tolerability of a drug and the best way of administering the drug to patients.
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