Treatment of Stage II Ovarian Cancer
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)
Stage II ovarian cancer is limited to the ovaries and other pelvic organs, but has not spread to the upper abdomen, lymph nodes or sites outside the abdomen. Each person with stage II ovarian cancer is unique, 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.
The combination of cytoreductive surgery and chemotherapy treatment is the standard of care for treatment of stage II ovarian cancer. Individuals with stage IIA disease experience cancer recurrence rates of 30-40% and those in patients with more advanced stage IIB disease are even greater. This is because patients with stage II ovarian cancer are often left with microscopic disease following surgery and currently available chemotherapy is unable to eradicate all of the remaining cancer.
Surgical cytoreduction (also called debulking) refers to the surgical removal of as much of the cancer as possible. Cytoreduction 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 cytoreduction live longer and have a longer time to cancer recurrence than patients who have had suboptimal cytoreduction.
Following cytoreductive surgery, all patients with stage II ovarian cancer are offered additional systemic treatment with the goal of destroying any remaining cancer not removed by surgery. Currently, this treatment is chemotherapy.
Doctors have also looked at initiating treatment before surgery 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.
Adjuvant Systemic Therapy
The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, precision cancer medicines, radiation therapy and/or immunotherapy.
Adjuvant chemotherapy is administered to decrease the risk of cancer recurrence following recovery from surgery because clinical trials have demonstrated that adjuvant chemotherapy improves survival compared to treatment with surgery alone. Standard systemic therapy typically consists of a platinum and taxane chemotherapy drug, however several other chemotherapy and precision cancer medicine drugs are available and others are being developed in clinical trials.
Because many patients still experience recurrence of their cancer following standard therapy, patients should consider participation in clinical trials evaluating new treatment approaches as their initial option.
Before deciding to receive adjuvant systemic therapy treatment or to participate in a clinical trial, women should ensure they understand the answer to 3 questions:
- What is my prognosis (risk of cancer recurrence) without adjuvant therapy treatment?
- How will my prognosis be improved with adjuvant treatment?
- What are the risks of treatment?
Upon completion of adjuvant systemic therapy doctors perform a series of tests o determine the effectiveness of treatment. These typically include a CT or MRI of the chest/abdomen/pelvis and a CA-125. The cancer will either be undetectable (a complete response) or still present. If cancer remains additional therapy for recurrent or resistant disease will be offered.
If a complete response or remission is achieved patients should discuss the potential benefits of additional maintenance therapy with their doctor. This is a lower dose therapy designed to prolong the remission and improve the chance of cure.
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. In addition to continued development of chemotherapy treatment regimens active investigation aimed at improving the treatment of early stage ovarian cancer includes the following:
Improvement of Adjuvant Chemotherapy: Clinical trials are currently ongoing to develop and compare adjuvant chemotherapy treatment regimens in women with Stage II ovarian cancer to improve outcomes.
Development of Precision Cancer Medicines: Research is ongoing to develop new medications that specifically target cancer cells in clinical trials. These trials typically require a sample of the cancer or liquid biopsy to be available in order to evaluate for biomarkers. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly. Learn more about development of precision cancer medicines for treatment of ovarian cancer.
PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. A new class of precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
PARP inhibitors have the greatest effect in women with mutations of the BRCA genes but may benefit additional patients with different genetic profiles as well. BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. The best way to incorporate PARP inhibitors into the overall management of ovarian cancer is being determined however they already have been shown to improve outcomes when used as maintenance therapy following completion of chemotherapy.1,2,3
Avastin® (bevacizumab: A targeted therapy that is showing promise in the treatment of ovarian cancer is Avastin®.4 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. Avastin may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.
Intraperitoneal (IP) Chemotherapy: This treatment approach 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 often 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.5,6
Maintenance Therapy: Consolidation therapy, also called maintenance therapy, refers to extra systemic therapy that is given after completion of standard adjuvant chemotherapy. Maintenance therapy with Taxol or the PARP inhibitor Zejula (Niraparib) have both been demonstrated to improve outcomes in select patients.1,7
Neoadjuvant Chemotherapy: Neoadjuvant chemotherapy refers to chemotherapy that is given 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.
2 Shapira-Frommer R, Oza AM, Domchek SM, et al. A phase II open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation. Journal of Clinical Oncology. 33, 2015 (supplement; abstract 5513).
3 Tesaro Inc., press release. Tesaro’s niraparib significantly improved progression-free survival for patients with ovarian cancer in both cohorts of the phase 3 NOVA trial. Available at: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.
4 (2016.) FDA Approves Genetech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer. [Press release.] Can be retrieved from https://www.gene.com/media/press-releases/14647/2016-12-06/fda-approves-genentechs-avastin-bevacizu
7 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;