By Lea Simms and Laura Gottschalk, PhD, Cancer Prevention & Treatment Fund
Ovarian cancer is the 5th leading cause of cancer death in women in the U.S. Approximately 21,000 women will receive a new diagnosis of ovarian cancer in 2015. 
Ovarian cancer begins in or near the ovaries, which is part of the female reproductive system. There are two ovaries, one on either side of the uterus, connected to the uterus by the fallopian tubes. Ovarian cancer is often undetected until it has spread to the uterus, pelvis, and abdomen.
Like all cancers, treatment is much more successful in the early stages when the cancer has not yet spread. Women over the age of 55, women who have a family history of breast or ovarian cancer, and women who have had trouble getting pregnant or have never been pregnant are all at increased risk for ovarian cancer.
To find out more about who is at risk and what to do about it, see our article Ovarian Cancer: who should be concerned and what can they do?
Traditionally, there have been three different types of ovarian cancer described:
- Germ cell
Epithelial tumors are the most common type: 85%-90% of all ovarian cancers are epithelial.These tumors start from the layer of cells that cover the outside of the ovaries or line the inside of the fallopian tubes, and can then spread to other parts of the body. There are four different types of epithelial ovarian cancer: serous (the most common), mucinous, endometroid, and clear cell. These different types of epithelial cancer describe how the tissue looks under the microscope and also the behavior of the cancer.
Germ cell tumors are a rarer form of ovarian cancer, in which the tumor starts growing in the germ cells that produce the eggs. Germ cell tumors make up about 2% of ovarian cancer cases and have a very high survival rate of 90%. This type of cancer is most commonly seen in women under 25 years old (ovarian cancer research fund). There are several types of germ cell tumors: teratomas, dysgerminomas, endodermal sinus tumors, and choriocarcinomas.
There are also stromal tumors which begin in the tissue cells that hold the ovary together. Stromal tumors are diagnosed in about 1% of women with ovarian cancer and have a high survival rate of 75%.
Like most cancers, ovarian cancer is probably not a single disease, but is made up of several different types of cancer that start in different places in or near the ovaries. Each type of cancer has its own unique genetic make-up, place where it begins to grow, and way of spreading. For example, the most common form of ovarian cancer, high-grade serous carcinoma, is now thought to start in the fallopian tube instead of the ovary . New treatments for ovarian cancer are in the early stages, but the goal is to develop treatment options for these specific types of ovarian cancer.
Benign ovarian tumors are not cancerous and can be treated by removal of all or a part of an ovary. Tumors that are cancerous can metastasize (spread) and can be fatal. The stage of the tumor is used to describe how much it has spread ranging from stage I (only within the ovary or fallopian tube and has not yet spread) to stage IV (has spread to outside organs like the liver or lungs). The grade classifies the tumor on how much it looks like normal tissue: 1 is the most like normal tissue and 3 is the least like normal tissue. These classifications are used to determine what treatment is recommended.
If you were diagnosed with ovarian cancer, your medical team will recommend one or more treatment options. The main treatments for ovarian cancer are:
The most common recommendation for all stages of ovarian cancer is surgery followed by chemotherapy.
Surgery for epithelial ovarian cancer has two main goals: to stage and debulk (remove) the tumor. Staging refers to the doctors looking to see how far the cancer has spread and then taking tissue samples to test in a lab. Usually this means the doctor will remove the ovaries, uterus, cervix, fallopian tubes and omentum (fatty tissue around these organs), and then remove tissue and fluid samples from the abdominal cavity and pelvis. The surgeon will then remove as much of the tumor as possible, which is called debulking. If the disease seems to be limited to one or both ovaries, the surgeon will biopsy the pelvis and abdomen to find out if the cancer has spread. Sometimes debulking is not possible because the patient is not healthy enough or the tumor may be attached to other organs. In these cases, chemotherapy will be used to treat the cancer that can’t be surgically removed.
Research has shown that if the cancer is caught early enough, a woman can be safely treated without removing her uterus (read more about it http://dev.stopcancerfund.org/p-ovarian-cancer/patients-under-50-with-early-stage-ovarian-cancer-safe-treatment-with-no-loss-of-fertility/). Women with later stage ovarian cancer usually must undergo surgery that removes the uterus and thus causes infertility.
For germ cell tumors and stromal tumors the main goal of surgery is to remove the cancer. Germ cell tumors are usually treated with a hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of ovaries and fallopian tubes). If the cancer is found in one ovary, then only one of the ovaries and a fallopian tube will be removed to preserve the woman’s fertility. Stromal tumors are treated by removing the cancerous ovary, unless the cancer has spread to other areas, in which case a hysterectomy or bilateral salpingo-oophorectomy will be performed.
After surgery, patients with epithelial ovarian cancer are treated with chemotherapy. Typical chemotherapy is a combination of 2 or more drugs, every 3-4 weeks, with 3-6 cycles. A cycle is a schedule of regular doses of drugs followed by a rest period.
The chemo drugs are given by mouth, injected into a vein (Intravenous chemotherapy also known as IV), or injected through a catheter directly into the abdomine (called intraperitoneal chemotherapy or IP). IP therapy works by bringing the toxic drugs in a concentrated form to exactly where the cancer is, while IV therapy aims to kill cancer cells wherever they might be located. In 2006, researchers reported that on average, patients receiving IP chemotherapy lived 65 months, compared to 50 months for patients receiving IV chemo only . That is why the National Cancer Institute currently recommends IP administration of chemo to treat ovarian cancer. However, this recommendation may soon change. In 2016, a study of 1,560 ovarian cancer patients surprisingly found no difference in survival for women receiving IP chemo compared to other traditional methods . This is important because IP therapy tends to cause worse side effects.
Although IP and IP/IV administration has been shown to have benefits and has been recommended by the National Cancer Institute, the combination tends to have worse side effects. That is probably why most eligible patients do not receive a combination of IP and IV chemotherapy.
There are many different types of chemotherapy drugs and research has shown that giving a combination of drugs in the initial treatment of ovarian cancer is more effective. Most doctors prescribe a platinum compound such as cisplatin or carboplatin and a taxane compound such as paclitaxel or docetaxel. A very large study in 2006 compared 198 clinical trials of 48,440 women being treated for ovarian cancer and found that the regimen that best prolonged survival is a platinum and taxane combination with intraperitoneal administration.
Hormones or hormone-blocking drugs can stop the growth of tumors. Tamoxifen is an anti-estrogen drug that is common in the treatment of breast cancer and some ovarian stromal tumors. There have been no large studies of Tamoxifen for ovarian cancer, however. It is generally used as a second-line therapy for recurrent stromal tumors or tumors that do not respond to standard chemotherapy. Since side effects are generally mild, it is considered a less toxic choice for women who cannot tolerate the side effects of standard chemotherapy. However, tamoxifen can increase the risk of serious blood clots in the legs, so patients should be aware of this risk before considering it.
Targeted therapy uses genetically engineered drugs such as bevacizumab (Avastin) and olaparib (Lynparza) to attack the cancer cells. In several studies, Avastin has been shown to have some effectiveness in delaying the progression of ovarian cancer but it is not clear whether it helps patients live longer, and it has substantial side effects that can harm quality of life.
Olaparib (Lynparza) is approved by the FDA for the treatment of ovarian cancer in women with BRCA1 or BRCA2 mutations as a last resort for women who have had three or more prior unsuccessful treatments of chemotherapy. It has not been proven safe or effective for other ovarian cancer patients, but two studies are underway to see if the drug can be a useful treatment for women with BRCA mutations who have previously tried at least one platinum-based chemotherapy treatment.
Radiation therapy is not common for ovarian cancer. Radiation therapy uses high energy x-rays or particles to kill the cancer cells. It is sometimes used for recurrent cases when the cancer is confined to a small area.
Which types of treatment you and your doctor decide to go with depends on the type of ovarian cancer you have and how it has advanced.
Clinical trials are used to help find new treatments for cancer. If more effective treatments are found through clinical trials, they may become the standard treatment. If the new treatment is found to be less effective or have worse side effects, it probably will not be approved by the FDA and will not be available in the future. Patients can enter clinical trials at different stages of their cancer treatment, but some trials may only be open to patients who have not yet started treatment. Remember: the treatments tested in clinical trials are not proven to be effective and the side effects are often unknown. The new treatment may be worse than standard treatments, better, or identical in terms of effectiveness or side effects. For those reasons, clinical trials are usually chosen by patients who have no other good options for treatment. See here for the National Cancer Institute’s list of clinical trials: http://www.cancer.gov/about-cancer/treatment/clinical-trials.
The Latest Research
New research suggests that the most common route of treatment (first surgery, then chemo) might not be the most effective route of treatment. There is now evidence that having chemotherapy first, then followed by surgery, may be more effective for women with ovarian cancer, especially with epithelial ovarian tumors. Research has shown that chemotherapy prior to surgery improved the debulking of the tumor and that patients also had fewer surgical complications and better post-operative recovery.
The latest research, by Dr. Sean Kehoe and his team of doctors, took place in 87 hospitals in the UK and New Zealand. The study randomly assigned 552 women with stage III or IV ovarian cancer to either the “Primary Surgery Group” (surgery followed by 6 cycles of chemotherapy) or to the “Primary Chemotherapy Group” (3 cycles of chemotherapy, then surgery followed by 3 more cycles of chemotherapy). The study measured overall survival rate as well as progression free survival (delaying the spread of cancer) and quality of life. At the conclusion of the study, 231 patients in the primary surgery group had died as had 220 in the primary chemotherapy group. Although the number of patients that died was similar, the Primary Chemotherapy group lived 1.5 months longer on average and had fewer adverse side effects and fewer toxic effects than the Primary Surgery group. The median survival rate (how long they lived after treatment) for the Primary Surgery group was 22.6 months compared to 24.1 months for the Primary Chemotherapy group. These results are also consistent with observational studies that showed similar results in survival rates.
Although the differences in survival rate and duration of survival were similar, the chemotherapy group did have marginally better outcomes. This new finding may change the way doctors treat ovarian cancer and gives women another option rather than immediate surgery.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
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