Stage III Ovarian Cancer
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Patients diagnosed with stage III ovarian cancer have cancer that has spread from the ovaries and pelvic organs into the upper abdomen or lymph nodes. Stage III ovarian cancer has not spread to sites outside the abdomen or inside the liver. The following is a general overview of the diagnosis and treatment of ovarian cancer. Each person with ovarian cancer is different, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
Currently, the standard treatment for stage III ovarian cancer consists of both surgery and chemotherapy. Unfortunately, less than 40% of patients experience long-term survival following standard treatment. This is because stage III ovarian cancer is often difficult to remove completely with surgery and currently available chemotherapy is unable to eradiate all of the remaining cancer.
During cytoreductive surgery (also called debulking), physicians attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by chemotherapy and therefore, decreases the likelihood of the cancer developing a resistance to chemotherapy. Initial cytoreductive surgery in ovarian cancer is currently considered the standard of care because clinical studies have shown that patients who have had optimal cytoreductive surgery live longer and have a more prolonged time to cancer recurrence than patients who have had suboptimal cytoreductive surgery .
Following cytoreductive surgery, all patients with stage III ovarian cancer are offered additional treatment. This is because approximately 60-80% of patients with stage III cancer will experience a recurrence of their cancer, even after complete surgical removal of cancer. Nearly all patients with stage III disease have small amounts of undetectable cancer that have spread outside the ovary and were not removed by surgery. Other patients cannot achieve optimal cytoreduction with initial surgery. An effective treatment is needed to eliminate the remaining cancer in order to improve the cure rate achieved with surgical removal of the cancer. Currently, this treatment is chemotherapy.
The combination of cytoreductive surgery and chemotherapy treatment is the standard of care for treatment of stage III ovarian cancer. Researchers have also looked at initiating treatment with neoadjuvant chemotherapy, in order to decrease the tumor burden, then performing cytoreductive surgery, followed by several more cycles of adjuvant chemotherapy. This format has been compared with the more traditional sequence of surgery followed by adjuvant chemotherapy. Most research has not shown a benefit to the chemo-surgery-chemo format, although some work is looking at whether this format might be applicable to patients who are suspected of having potentially unresectable disease. In this case, current guidelines recommend chemotherapy for three cycles, followed by an interval cytoreductive surgery, and then the final three cycles of chemotherapy. Researchers are also continuing to evaluate the use of a second or interval cytoreductive surgery to be performed after the chemotherapy has had a chance to further decrease the amount of cancer.
Chemotherapy for Stage III Ovarian Cancer
It is important to understand that many patients with ovarian cancer already have small amounts of cancer that were not removed with surgery or have spread away from the ovaries. These cancer cells cannot be detected with any of the currently available tests and are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy and/or biologic therapy.
Clinical trials have demonstrated that for patients with advanced stage ovarian cancer, treatment with combination chemotherapy regimens containing a platinum (Platinol® or Paraplatin®) compound prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with surgery and non-platinum compounds. Current adjuvant chemotherapy typically consists of a taxane and a platinum compound administered every 3 weeks for 6 cycles.
Unfortunately, fewer than 20% of patients treated with a platinum compound and paclitaxel survive without evidence of cancer recurrence 5 years following treatment. Because many patients still experience recurrence of their cancer following standard therapy, some patients and their doctors consider participation in clinical trials evaluating new treatment approaches as their initial option.
Intraperitoneal (IP) chemotherapy delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. This treatment appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half an inch (this is sometimes referred to as “optimally debulked”).
Among women with optimally debulked Stage III ovarian cancer, a phase III clinical trial compared treatment with intravenous (IV) chemotherapy alone to treatment with both IV and IP chemotherapy. Women who received both IV and IP chemotherapy survived more than a year longer than women who received only IV chemotherapy, but also experienced more severe side effects such as fatigue, pain, and low blood counts.
According to a statement by the American College of Obstetricians and Gynecologists, “the decision to use IP chemotherapy must be individualized.” The combination of IV and IP chemotherapy appears to improve survival among women with optimally debulked Stage III ovarian cancer, but at the cost of increased side effects. Researchers continue to search for ways to reduce side effects and catheter problems among women treated with IP chemotherapy.
Strategies to Improve Treatment
The progress that has been made in the treatment of ovarian cancer has resulted from improved development of adjuvant chemotherapy treatments and doctor and patient participation in clinical studies. Future progress in the treatment of ovarian cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of stage III ovarian cancer.
Targeted Therapy: Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.
A targeted therapy that is showing promise in the treatment of ovarian cancer is Avastin® (bevacizumab). Avastin slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Due to its effects on blood vessels, Avastin may also improve the delivery of chemotherapy to the cancer.
Consolidation Therapy: Consolidation therapy, also called maintenance therapy, refers to extra chemotherapy that is given after completion of standard chemotherapy. Consolidation therapy is currently being explored in clinical trials; a question of interest is whether the survival benefit (if any) will outweigh the side effects that accompany prolonged treatment
Dose-Dense Treatment: Rapid administration of several different single chemotherapy compounds at the maximum tolerated dose allows higher doses of chemotherapy to be delivered and may prevent cancer cells from developing chemotherapy resistance. Dose-dense treatment approaches are being evaluated in clinical trials.
High-Dose Chemotherapy and Autologous Stem Cell Transplant: Chemotherapy targets and kills rapidly dividing cells such as cancer cells. High- dose chemotherapy (HDC) kills more cancer cells than lower-dose conventional chemotherapy. Unfortunately, HDC also kills more normal cells, especially the blood-producing stem cells in the bone marrow. Stem cells are immature cells produced in the bone marrow, which is the spongy material inside bones. Stem cells eventually become either red blood cells, which provide oxygen to tissues, white blood cells, which fight infection; or platelets, which aid in blood clotting.
HDC destroys cancer as well as bone marrow stem cells. When bone marrow is destroyed, stem cell stores are depleted, which leads to low levels of circulating blood cells. When these cells reach critically low levels, complications such as anemia, infection and bleeding can occur. As these complications could result in death, it is imperative to restore stem cell levels as quickly as possible. Stem cell transplantation is an attempt to restore the blood-producing stem cells after HDC has reduced them to dangerously low levels. In autologous stem cell transplantation, the patient’s own stem cells are collected before chemotherapy treatment, frozen, and infused back into the patient after treatment to “rescue” the bone marrow.
Researchers from the Autologous Blood and Marrow Transplant Registry evaluated over 400 women with advanced ovarian cancer who received HDC and autologous stem cell transplantation as part of their treatment. Two years following treatment, the overall survival rate for patients in this study was 35%. There was a subgroup of these patients who had a survival rate of 55% after two years. These women were younger and in otherwise good health, possessed a certain microscopic type of cancer cell (non-clear cell) and were treated with HDC and stem cell transplantation during their first remission. The results from this study indicate patients with advanced ovarian cancer who undergo HDC and autologous stem cell transplant may experience improved survival times, particularly when this treatment strategy is used early in a patient’s treatment course.
Neoadjuvant Chemotherapy: Neoadjuvant refers to the administration of anti-cancer chemotherapy prior to surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval cytoreduction. Some doctors believe that neoadjuvant chemotherapy can reduce the size of the cancer, thereby allowing easier surgical removal and more effective results from the subsequent chemotherapy. Although ongoing work is being done to explore the neoadjuvant chemotherapy-surgery-adjuvant chemotherapy format, current results do not suggest that this format shows an advantage over the more conventional format of surgery followed by adjuvant chemotherapy. There are current clinical trials attempting to further define the answer to this question.1
Combined Approaches: Combining one or more new strategies may offer the greatest hope for patients. For example, a patient could receive dose-dense induction chemotherapy, followed by interval debulking and high-dose chemotherapy and autologous stem cell transplant, which together should produce the highest chance of achieving a complete remission. Patients in remission could then receive additional treatment with anti-cancer agents, such as maintenance chemotherapy or other biologic agents. Many combinations are being evaluated in clinical trials.
When Deciding on Treatment, Patients Should Ask the Following Questions:
Is there any evidence that the new treatment may be an improvement over conventional treatment? Since over 50% of patients with stage III disease may experience cancer recurrence, it may not be useful to compare the response rate to chemotherapy, the average duration of survival or time to relapse.
Instead, when evaluating treatment strategies, patients may want to compare the percentage of patients surviving with or without relapse 3-5 years from treatment to determine whether a treatment is truly more effective.
What is known about the risks or side effects of the new treatment? It is important to understand that patients experience more side effects with each treatment they receive. Since few patients with metastatic cancer are cured with standard initial treatment, prolonging the decision to receive a new treatment may result in greater side effects and a lesser chance of benefit.
 Coleman, RL, Gershenson DM. “Neoplastic diseases of the ovary: Screening, benign and malignant epithelial and germ cell neoplasms, sex-cord stromal tumors. In: Katz VL, ed. Comprehensive Gynecology, 5th ed. St. Louis: Mosby; 2007: 839-77.
 Armstrong DK, Bundy B, Lenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. New England Journal of Medicine. 2006;354:34-43.
 ACOG Committee on Gynecologic Practice. Intraperitoneal chemotherapy for ovarian cancer. Obstetrics and Gynecology. 2008;111:249-251.
 Spannuth WA, Sood AK, Coleman RL. Angiogenesis as a strategic target for ovarian cancer therapy. Nature Clinical Practice Oncology. 2008;5:194-204.
 Markman M, Liu PY, Wilczynski S et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: A Southwest Oncology Group and Gynecologic Oncology Group trial. Journal of Clinical Oncology. 2003;21:2460-65.