Stages of Cervical Cancer
Stage I Cervical Cancer
Overview
Treatment of stage I cervical cancer may include surgery, radiation, chemotherapy or precision cancer medicines.
Stage I cancer of the cervix is commonly detected from an abnormal Pap smear or pelvic examination. Following a staging evaluation, a stage I cancer is said to exist if the cancer is confined to the cervix. Stage I cervical cancer is curable for the majority of patients if surgery, radiation, and chemotherapy are appropriately used.
A variety of factors ultimately influence a patient’s decision to receive treatment. The potential benefits of each cancer treatment must be carefully balanced with the potential risks. The following is an overview of the treatment of stage I cervical cancer. The information is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
Stage IA cervical cancer
Treatment of stage IA cervical cancer typically consists of surgical removal of the cancer. This can be accomplished with a hysterectomy or a conization procedure. A simple hysterectomy involves surgical removal of the uterus, including the cervix and a small amount of surrounding normal tissue. This can be performed through a low abdominal incision (below the belly button and above the pelvic bone) or through the vagina, which avoids an abdominal incision. A simple hysterectomy is very effective therapy for most stage IA cervical cancers.
Women with stage IA cervical cancer who wish to have children in the future may elect to undergo a procedure called a conization. In a conization procedure, the surgeon removes only a portion of the cervix in the operating room. If the cancer is completely removed, no additional surgery is necessary. If cancer is detected at the edge of the removed specimen, a complete hysterectomy is required.
To learn more about surgical treatment and its side effects, go to Surgical Management of Cervical Cancer.
Some patients do not want to or cannot undergo an operation such as a hysterectomy because of co-existing medical conditions. For these patients, radiation therapy can be used to treat the cancer. The possible complications and the relative inconvenience usually determine whether surgery or radiation is the most appropriate treatment. For example, surgery is a one-time procedure, whereas external beam radiation therapy requires 3-6 weeks of daily treatments and implant radiation may require additional hospitalization time.
Implant radiation is a procedure that is performed in the operating room and involves the placement of radioactive material or seeds in or near the cancer. This process may be repeated depending on the necessary radiation dose. Radiation therapy appears to be as effective as surgery in curing stage IA cervical cancer.1
To learn more about radiation therapy and its side effects, go to Radiation Therapy for Cervical Cancer.
Approximately 95% of patients with stage IA cervical cancer survive without evidence of cancer recurrence 10 years after surgery or radiation therapy. Less than 5% of patients with stage IA cervical cancer experience recurrence.
Stage IB cancer of the cervix
Small stage IB cervical cancers can be successfully cured with hysterectomy or radiation therapy in approximately 90% of patients. Bulky stage IB cancers (greater than 4 centimeters in size) are only cured in 70-75% of patients when surgery or radiation therapy is administered alone. Bulky stage IB cancers are best treated with combined modality therapy using radiation, surgery and chemotherapy.2,3
Before a hysterectomy is performed in a patient suspected of having a stage IB cancer, the doctor will often remove the lymph nodes in the pelvis to see if they contain cancer. This is called a pelvic lymph node dissection. If the lymph nodes contain cancer, the surgeon will not usually proceed with a hysterectomy because treatment over a larger area is necessary to destroy all the cancer cells. Radiation therapy and chemotherapy are generally recommended.
Even with surgical removal of all visible cancer, 10% of patients with small stage IB and 30-40% of patients with bulky stage IB cancers will experience a recurrence. This is because some patients already have small amounts of cancer that spread outside the cervix 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 micrometastases or residual cancer causes the relapses that follow treatment with surgery alone.
In order to improve the cure rate of cervical cancer, it is important to develop strategies to cleanse the body of micrometastases and prevent recurrences. Adjuvant therapy is additional treatment that increases the effectiveness of a primary therapy. The goal of adjuvant treatment is to improve the chance of a cure, prevent cancer from recurring and/or to improve the duration of overall survival. Adjuvant therapy may consist of radiation, chemotherapy or other treatments. The role of adjuvant treatment for small stage IB cancers is not clear; however, patients with bulky stage IB cancers have improved survival if treated with adjuvant therapy.1
A clinical study conducted by the Gynecologic Oncology Group demonstrated a reduction in cancer recurrence when radiation therapy was used after radical hysterectomy for patients with high-risk stage IB cancer of the cervix. Patients treated with external beam radiation therapy to the pelvis were directly compared with a group of patients who received no radiation therapy. The results indicated that patients treated with adjuvant radiation therapy after surgery experienced a cancer recurrence rate of 12%, compared to 21% in patients treated with surgery alone. The addition of adjuvant radiation therapy reduced the chance of cancer recurrence by almost 50% in this study.
Adjuvant therapy can also consist of combined treatment with external beam radiation therapy and chemotherapy. Patients with cancer cells in the pelvic lymph nodes or cancer at the edge of the surgical specimen may additionally benefit from treatment with combined radiation therapy and chemotherapy. Several chemotherapy drugs including Platinol® and 5-fluorouracil have the ability to kill cancer cells directly and increase the effectiveness of radiation therapy in killing cancer cells.
The New England Journal of Medicine published the results of a clinical study that compared adjuvant treatment with radiation only to treatment with radiation and concurrently administered Platinol® chemotherapy following surgical hysterectomy in patients with high-risk stage IB cancers. Patients treated with chemotherapy and radiation after surgery were more likely to survive without cancer recurrence. At 3 years from treatment, 80% of patients receiving combined radiation and chemotherapy were alive without recurrence, compared to only 63% of patients treated with radiation alone. Currently, the combination of surgery, radiation and chemotherapy appears to produce the best results for treatment of patients with high-risk stage IB cervical cancer.2
Strategies to Improve Treatment
The progress that has been made in the treatment of cervical cancer has resulted from improved development of treatments in patients with more advanced stages of cancer and participation in clinical trials. 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 stage I cervical cancer.
Preservation of reproductive function
Generally, women who receive treatment for stage I cervical cancer have an excellent prognosis, with a cure rate of greater than 90% following a hysterectomy. However, some women of childbearing age would prefer a therapy that preserves their reproductive function. One procedure for preserving reproduction function is a radical trachelectomy, which only removes a portion of the uterus. In a recent clinical study, 32 patients with stage I cervical cancer measuring 2cm or less treated with radical trachelectomy experienced a 2-year survival rate of 95%, without any relapse of the cancer. Approximately 40% of women were able to conceive after treatment.4
New adjuvant chemotherapy regimens
Platinol® chemotherapy administered concurrently with radiation improves the survival of women with stage IB bulky cervical cancer. Evaluation of new chemotherapy drugs in addition to or in place of Platinol® that can kill cancer cells more effectively are now being tested as adjuvant therapies.
Neoadjuvant therapy
The practice of administering treatment before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, making it easier to remove with surgery. With the development of new chemotherapy regimens and radiation therapy, clinical trials of neoadjuvant therapy performed in patients with cervical cancer are currently ongoing.
The use of radiation prior to a simple hysterectomy is being evaluated in clinical trials for patients with larger stage IB cervical cancers. This combination of treatment appears to reduce the chance of a cancer recurrence in the area of the cancer by removing cancer cells that may have survived through the radiation therapy.
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.
References
1 NCCN Guidelines Treatment by Cancer Type
2 Rotman M, Sedlis A, Piedmonte M, et al. A Phase III Randomized Trial of Postoperative Pelvic Irradiation in Stage IB Cervical Carcinoma with Poor Prognostic Features: Follow-Up of a Gynecologic Oncology Group Study. International Journal of Radiation Oncology, Biology and Physics. 2006; 65: 169-176.
3 Gynecologic Oncology, Vol 73, No 2, pp 177-183, 1999.
4 Cancer, Vol 86, No 11, 1999
Stage II Cervical Cancer
Overview
Treatment of stage II cervical cancer may include surgery, radiation, chemotherapy or precision cancer medicines.
Cervical cancer diagnosed as stage II disease is commonly detected from an abnormal Pap smear or pelvic examination. Following a staging evaluation of cervical cancer, a stage II cancer is said to exist if the cancer has extended beyond the cervix to the upper portion of the vagina (stage IIA) or to the tissues next to the cervix, called the parametria (stage IIB). Patients with stage II cervical cancer are generally treated with a combination of radiation therapy and chemotherapy. Some patients with stage IIA disease can undergo a radical hysterectomy, sometimes followed by a course of radiation therapy. The following is an overview of the treatment of stage II cervical cancer. The information is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
Stage II 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 via a machine that aims x-rays at the body (external beam radiation) and/or by placing small capsules of radioactive material directly into and near the cervix (internal or implant radiation). Most patients will receive both types of radiation therapy during their course of treatment. External beam radiation therapy (EBRT) for cervical cancer is administered on an outpatient basis for approximately 4 to 6 weeks.1
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.
The addition of chemotherapy (anti-cancer drugs) has improved long-term outcomes in some patients with cervical cancer. Chemotherapy 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. Clinical studies performed in patients with locally advanced cervical cancer utilizing concurrent chemotherapy and radiation therapy have improved remission rates and prolonged survival.1
Radiation therapy plus concomitant chemotherapy appears superior to radiation therapy alone. The 5-year survival rate of patients with stage IB, IIA, or IIB cervical cancer was 77% for patients treated with concurrent radiation therapy and chemotherapy, compared to only 50% for patients treated with radiation therapy alone. Concurrent chemotherapy and radiation therapy were well tolerated except for minor gastrointestinal and hematologic side effects, which were reversible. 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.1,2
Even with combination chemotherapy and radiation treatment, approximately 20-40% of patients with stage II cervical cancer experience recurrence of their cancer because cancer cells may have survived near the cancer despite the radiation therapy or small amounts of cancer may have spread outside the cervix and were not treated by the chemotherapy. These cancer cells cannot be detected and are referred to as micrometastases. The presence of these microscopic areas of cancer or surviving cancer cells can cause the relapses that follow treatment.
Strategies to Improve Treatment
The progress that has been made in the treatment of cervical cancer has resulted from improved development of treatments in patients with more advanced stages of cancer and participation in clinical trials. 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 stage II cervical cancer.
New adjuvant chemotherapy regimens
Platinol® chemotherapy administered concurrently with radiation improves the survival of women with stage II cervical cancer. Evaluation of new chemotherapy drugs in addition to or in place of Platinol® that can kill cancer cells more effectively are now being tested as adjuvant therapies.3
Neoadjuvant therapy
The practice of administering treatment before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, making it easier to remove with surgery. With the development of new chemotherapy regimens and radiation therapy, clinical trials of neoadjuvant therapy performed in patients with cervical cancer are currently ongoing.
The use of radiation prior to a simple hysterectomy is being evaluated in clinical trials for patients with larger stage IB cervical cancers. This combination of treatment appears to reduce the chance of a cancer recurrence in the area of the cancer by removing cancer cells that may have survived through the radiation therapy.
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.
Immunotherapy
The immune system is an elaborate network of cells and organs that protect the body from infection. The immune system is also part of the body’s innate disease-fighting capability to treat cancer. With cancer, part of the problem is an ineffective immune system. The immune system recognizes cancer cells as foreign and up to a point can get rid of them or keep them in check. Cancer cells are very good at finding ways to hide from, suppress, or wear out the immune system and avoid immune destruction. The immune system may not attack cancer cells because it fails to recognize them as foreign and harmful.
The goal of immunotherapy is to help the immune system recognize and eliminate cancer cells by either activating the immune system directly, or by inhibiting mechanisms of suppression of the cancer.
General types of immunotherapy include interferon, interleukin, and colony stimulating factors (cytokines), which generally activate the immune system to attack the cancer. These general immunotherapies however are not specific and their activation of the immune system can cause severe side effects by attacking normal cells along with cancer cells. Immunotherapy treatment of cancer has progressed considerably over the past 30 years and has evolved from a general to more precisely targeted immunotherapy treatment. Examples of precision immunotherapy include checkpoint inhibitors, CAR T cells, and vaccines.
In an attempt to improve the chance of cure, immunotherapies are being tested alone or in combination with chemotherapy in clinical trials.
References
1 NCCN Guidelines Treatment by Cancer Type
2 Duenas-Gonzalez A, Zarba JJ, Alcedo JC, et al. A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA5507.
3 Fachini AMD, Zuliani AC, Sarian LO, et al. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: a randomized controlled trial. Gynecol Oncol. Published online December 16, 2020. doi:10.1016/j.ygyno.2020.11.029
Stage III Cervical Cancer
Overview
Treatment of stage III cervical cancer may include surgery, radiation, chemotherapy or precision cancer medicines.
Cervical cancer diagnosed as stage III disease is commonly detected from an abnormal Pap smear or pelvic examination or from symptoms caused by the cancer. Following a staging evaluation, a stage III cancer is said to exist if the cancer has extended beyond the cervix to the lower portion of the vagina (stage IIIA), has extended to one or both sides of the pelvis (stage IIIB), or causes a blockage of drainage from the kidneys (stage IIIB). Patients with stage III cervical cancer are generally treated with radiation therapy and chemotherapy. The following is an overview of the treatment of stage III cervical cancer. The information is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
Stage III cervical cancer is currently best managed with 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 into or 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.1,2
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.
The addition of chemotherapy (anti-cancer drugs) has improved long-term outcomes in patients with cervical cancer. Chemotherapy 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. Clinical studies performed in patients with locally advanced cervical cancer utilizing concurrent chemotherapy and radiation therapy have improved remission rates and prolonged survival.1
Radiation therapy plus concomitant chemotherapy appears superior to radiation therapy alone. The 5-year survival rate of patients with stage IB, IIA, or IIB cervical cancer was 77% for patients treated with concurrent radiation therapy and chemotherapy, compared to only 50% for patients treated with radiation therapy alone. Concurrent chemotherapy and radiation therapy were well tolerated except for minor gastrointestinal and hematologic side effects, which were reversible. 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.1,2,3
Even with combination chemotherapy and radiation treatment, approximately 20-40% of patients with stage II cervical cancer experience recurrence of their cancer because cancer cells may have survived near the cancer despite the radiation therapy or small amounts of cancer may have spread outside the cervix and were not treated by the chemotherapy. These cancer cells cannot be detected and are referred to as micrometastases. The presence of these microscopic areas of cancer or surviving cancer cells can cause the relapses that follow treatment.
Strategies to Improve Treatment
The progress that has been made in the treatment of cervical cancer has resulted from improved development of treatments in patients with more advanced stages of cancer and participation in clinical trials. 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 stage II cervical cancer.
New adjuvant chemotherapy regimens
Platinol® chemotherapy administered concurrently with radiation improves the survival of women with stage III cervical cancer. Evaluation of new chemotherapy drugs in addition to or in place of Platinol® that can kill cancer cells more effectively are now being tested as adjuvant therapies.
Neoadjuvant therapy
The practice of administering treatment before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, making it easier to remove with surgery. With the development of new chemotherapy regimens and radiation therapy, clinical trials of neoadjuvant therapy performed in patients with cervical cancer are currently ongoing.
The use of radiation prior to a simple hysterectomy is being evaluated in clinical trials for patients with larger stage IB cervical cancers. This combination of treatment appears to reduce the chance of a cancer recurrence in the area of the cancer by removing cancer cells that may have survived through the radiation therapy.
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.
Immunotherapy
The immune system is an elaborate network of cells and organs that protect the body from infection. The immune system is also part of the body’s innate disease-fighting capability to treat cancer. With cancer, part of the problem is an ineffective immune system. The immune system recognizes cancer cells as foreign and up to a point can get rid of them or keep them in check. Cancer cells are very good at finding ways to hide from, suppress, or wear out the immune system and avoid immune destruction. The immune system may not attack cancer cells because it fails to recognize them as foreign and harmful.
The goal of immunotherapy is to help the immune system recognize and eliminate cancer cells by either activating the immune system directly, or by inhibiting mechanisms of suppression of the cancer.
General types of immunotherapy include interferon, interleukin, and colony stimulating factors (cytokines), which generally activate the immune system to attack the cancer. These general immunotherapies however are not specific and their activation of the immune system can cause severe side effects by attacking normal cells along with cancer cells. Immunotherapy treatment of cancer has progressed considerably over the past 30 years and has evolved from a general to more precisely targeted immunotherapy treatment. Examples of precision immunotherapy include checkpoint inhibitors, CAR T cells, and vaccines.
In an attempt to improve the chance of cure, immunotherapies are being tested alone or in combination with chemotherapy in clinical trials.
References
1 NCCN Guidelines Treatment by Cancer Type
2 Duenas-Gonzalez A, Zarba JJ, Alcedo JC, et al. A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA5507.
3 Fachini AMD, Zuliani AC, Sarian LO, et al. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: a randomized controlled trial. Gynecol Oncol. Published online December 16, 2020. doi:10.1016/j.ygyno.2020.11.029
Stage IV Cervical Cancer
Overview
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 Stage IV Cervical Cancer
Localized Stage IVA
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.
Metastatic Stage IVB
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.