|Ovarian Cancer: The Basics|
| Christopher Dolinsky, MD and Carolyn Vachani, MSN, RN, AOCN
Updated By: Lara Bonner Millar, MD
|Abramson Cancer Center of the University of Pennsylvania|
| Last Modified: January 14, 2012
What is the ovary?
The ovaries are two small organs that only women possess. They are located in a woman's pelvis, connected to her uterus (the organ where a baby grows and develops when a woman is pregnant) by the fallopian tubes. The ovaries are each about the size of a peanut M&M, and they can often be felt by your doctor during the bi-manual portion of a pelvic examination. A woman's ovaries are responsible for two important functions in her body: they produce female hormones and they produce eggs. Every month that a woman is fertile and not pregnant, her ovaries release a mature egg that travels into her uterus and has the potential to become fertilized. The ovaries also produce important hormones, namely estrogen and progesterone, which regulate a woman's menstrual cycles, influence the development of a woman's body during puberty, and keep a woman fertile.
What is ovarian cancer?
Ovarian cancer develops when cells in the ovaries begin to grow in an uncontrolled fashion with the potential to invade nearby tissues or spread throughout the body. Large collections of this "out-of-control" tissue are often referred to as tumors. However, some tumors are not really cancer because they cannot spread or threaten someone's life. These are called benign tumors or masses. The tumors that can spread throughout the body or invade nearby tissues represent true invasive cancer, and are called malignant tumors. The distinction between benign and malignant tumors is very important in ovarian cancer because many ovarian tumors are benign. Also, sometimes women (especially young women) can get ovarian cysts, which are collections of fluid in the ovaries that can occasionally grow large or become painful. However, ovarian cysts are not cancerous and should not be confused with ovarian cancer. Your doctor may suggest that you have an ovarian cyst removed if it is becoming bothersome.
Cancers are characterized by the cells from which they originally form. The most common type of ovarian cancer is called epithelial ovarian cancer; it comes from cells that lie on the surface of the ovary known as epithelial cells. Epithelial ovarian cancer comprises about 90% of all ovarian cancers and usually occurs in older women. About 5% of ovarian cancers are called germ cell ovarian cancers and arise from the ovarian cells that produce eggs. Germ cell ovarian cancers are more likely to affect younger women. Another 5% of ovarian cancers are known as stromal ovarian cancers and develop from the cells in the ovary that hold the ovary together and produce hormones. These tumors can create symptoms by producing a large excess of female hormones. Each of these three types of ovarian cancer (epithelial, germ cell, stromal) contains many different subtypes of cancer that are distinguished based on how the cells look under a microscope. Discuss the exact category of ovarian cancer that you have with your physician so that you can get a sense of the particulars of your case.
A rare type of cancer, called primary peritoneal cancer, is a malignant tumor arising from the peritoneum, the lining of the abdominal cavity. It tends to behave in a fashion very similar to ovarian cancer, and they can look identical under the microscope. The treatments used are often the same as those used for ovarian cancer. This type of cancer can develop in women with intact ovaries or in those who have had their ovaries removed.
Am I at risk for ovarian cancer?
As women get older, their risk of developing ovarian cancer increases. In the U.S., it was estimated that 21,990 women would develop ovarian cancer in 2011; and 15,460 women would die of ovarian cancer in 2011. Ovarian cancer accounts for 3% of all cancers in women, and is the 5th most common cause of cancer death for women in the U.S. Unfortunately, the majority of cases of ovarian cancer are found when it is advanced, because early stage ovarian cancers rarely cause any symptoms. It is for this reason that many researchers are interested in developing a screening test for ovarian cancer (see below).
Although there are several known risk factors for getting ovarian cancer, no one knows exactly why one woman gets it and another does not. The most significant risk factor for developing ovarian cancer is age; the older a woman is, the higher her chances are of having it. The majority of ovarian cancers are diagnosed in women after they have gone through menopause, in their late fifties and sixties. The average age for a woman to get a sporadic ovarian cancer (meaning not part of a familial syndrome) is 63 years old, although women with genetic or familial risk factors tend to get ovarian cancer at a slightly younger age (average age of diagnosis is 54 years). Less than 15% of ovarian cancers are diagnosed in women under age 50. Many of these cases are not epithelial (the most common type) and are not amenable to screening with CA125.
Other than age, the next most important risk factor for ovarian cancer is a family history of ovarian cancer, particularly if your family members are affected at an early age. If your mother, sister, or daughters have had ovarian cancer, then you have an increased risk for development of the disease. Scientists estimate that 7% to 10% of all ovarian cancers are the result of hereditary genetic syndromes. Genetic mutations for ovarian cancer have become a hot topic of research lately. Genetic syndromes that are recognized to increase ovarian cancer risk include hereditary nonpolyposis colorectal cancer syndrome (HNPCC), multiple endocrine neoplasia type 1 (MEN 1), breast and ovarian cancer syndrome (associated with mutations in either the gene BRCA1 or the gene BRCA2), Peutz-Jeghers syndrome, Gorlin syndrome, and site-specific ovarian cancer syndrome (which produces an increased risk for ovarian cancer alone). Women can inherit these mutations from their parents, and it may be worth testing for mutations if a woman has a particularly strong family history of breast or ovarian cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get the disease). Having a mutation doesn't necessarily mean a woman is going to get the disease, but it does greatly increase her chances above the general population. Family members may elect to be tested to see if they carry mutations as well. If a woman does have the mutation, she can get more rigorous screening, take preventive medications, or undergo prophylactic oophorectomies (preventive removal of your ovaries) to decrease her cancer risk. The decision to get tested is a highly personal one that should be discussed with a doctor or genetic counselor who is trained in counseling patients about genetic testing.
The rest of the risk factors for ovarian cancer are not as significant as age and family history/genetic syndromes, but are mentioned because some of them can be controlled. It appears that the more menstrual cycles (and thus ovulations) a woman has in her lifetime, the more likely she is to develop ovarian cancer. Thus women who started menstruating early, go through menopause late, don't have any children (or have children after age 30), don't use a form of birth control that stops menstruation/ovulation (like birth control pills), and/or who don't breastfeed are all more likely to develop ovarian cancer. It also appears that having a tubal ligation (having your tubes tied) and/or a hysterectomy (having your uterus surgically removed) decreases your risk of ovarian cancer. Prolonged use of the infertility drug, clomiphene citrate, without getting pregnant can also slightly increase a woman's risk for ovarian cancer. Finally, it has been suggested that a diet high in animal fats can increase a woman's risk for ovarian cancer. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get ovarian cancer. Talk to your doctor about your risk factors for ovarian cancer to understand his/her recommendations for screening and prevention.
How can I prevent ovarian cancer?
Unfortunately, there aren't very good screening methods for ovarian cancer, so preventing it is a particularly important challenge. If you are a woman without a family history/genetic syndrome, then the best way to prevent ovarian cancer is to alter whatever risk factors you have control over. For example, having children by age 30 and breastfeeding both reduce risk. Additionally, the use of oral contraceptives for 4 or more years is associated with an approximately 50% reduction in ovarian cancer risk in the general population. Bilateral tubal ligation and hysterectomy also decrease ovarian cancer risk. Keep in mind that any medication, including birth control pills, or surgical procedure, has its own risks and should not be taken lightly.
Women who are carriers of one of the above mentioned genetic syndromes face different decisions. They generally need to have more rigorous screening done for ovarian cancer, they may want to take a drug, such as tamoxifen, to reduce their risk, and some may elect to have their ovaries removed when they are still healthy (called a prophylactic oophorectomy). This should only be done when a woman is finished having children, and it can drastically reduce a woman's chances for developing ovarian cancer (but not reduce the risk to zero). Before a woman decides to do this, she should have genetic testing and a significant amount of counseling from a physician who has experience with genetic diseases.
While a diet high in animal fats has been implicated in ovarian cancer, a diet rich in fruits and vegetables may have a small preventive effect. It has been suggested that supplementation with vitamins A, C, and E may decrease your risk, but further studies need to be performed before any nutritional recommendations can be made regarding ovarian cancer prevention.
What screening tests are available?
The ideal screening test for ovarian cancer would save many lives. The vast majority of ovarian cancers are found at advanced stages, because early, small ovarian cancers are asymptomatic or have vague symptoms and cannot usually be found by a physician's exam. Patients who are diagnosed with early ovarian cancers tend to respond to treatment better than patients with more advanced cancers. Currently, there are not any effective approaches to ovarian cancer screening. There are a few tests that are being studied, but we need further data before they become routine for ovarian cancer screening.
Right now, the only screening that is recommended for the general population (women without hereditary cancer syndromes) is an annual pelvic examination. Your physician can usually feel your ovaries during the bi-manual portion of the exam, and if any abnormalities are felt, you can be referred for further tests. The major limitation to this method is that early ovarian cancers aren't usually appreciated on examination, and are often missed.
There are a few other tests that are currently being studied for ovarian cancer screening. One is a blood test that looks for a protein named CA-125. CA-125 is a protein that is shed from damaged ovary cells, and is often elevated in ovarian cancer. There are a few problems with CA-125 as a screening test. It is elevated in many other diseases and conditions besides ovarian cancer, including other cancers, endometriosis, fibroids, menstruation, colitis, diverticulitis, pancreatitis, lupus, and inflammation of the lining of the lung or heart. Only 50% of early stage ovarian cancers cause an elevated CA125, and non-epithelial ovarian tumors do not produce CA125.
One possible way to use CA-125 for ovarian cancer screening is to check it and then re-check it 6 months later. If it drastically increases over this time, then it is more suggestive of ovarian cancer, but the problem is that many patients without ovarian cancer will have elevated CA-125 levels and end up getting unnecessary further workup (which often means going for needless surgery). It can be dangerous to perform surgery unnecessarily, so we need a test that is more specific for ovarian cancer before it can be recommended for screening the general population.
Another investigational method for ovarian cancer screening is transvaginal ultrasonography. Ultrasound is an imaging technique that uses sound waves that bounce off of tissues and provide a picture of whatever is being investigated. By inserting an ultrasound probe into a woman's vagina, doctors can get a relatively good look at her ovaries. If the ovaries look suspicious, then further tests can be done. The biggest problem with using transvaginal ultrasound for ovarian cancer screening is the same problem as using CA-125; both tests cause too many healthy women to require unnecessary procedures because the tests are not specific enough for ovarian cancer. Doctors hoped that a combination of CA-125 and transvaginal ultrasound would be an effective method for ovarian cancer screening. However, results from a large study (United States National Institute of Health Prostate, Lung, Colorectal and Ovary Study) that combined both tests found that ovarian cancer mortality was not reduced by this screening approach. There is a second large, ongoing study of these tests called the UK Collaborative Trial of Ovarian Cancer Screening.
A urine screening test that identifies levels of a protein called Bcl-2 is in early clinical trials. Researchers have found that this protein was 10 times higher in women with ovarian cancer when compared to healthy individuals and those with benign ovarian disease. In early studies, the test detected 92% of ovarian cancers.
Currently, the general population should only be screened for ovarian cancer with a pelvic examination. However, women with a strong family history or those with a proven hereditary cancer syndrome may need to get more rigorous screening with serial CA-125 tests and/or transvaginal ultrasounds. Talk to your doctor about your ovarian cancer risk, and what the best way to go about screening is in your particular case.
What are the signs of ovarian cancer?
For many years, ovarian cancer has been called a "silent killer" because it was thought that symptoms did not develop until the disease was advanced. Recently, ovarian cancer experts found that this was not true, and most women had symptoms early on that were dismissed by themselves or their healthcare providers. Experts collaborated to develop the Ovarian Cancer Symptoms Consensus Statement, which describes important symptoms.
The symptoms that are more likely seen in women with ovarian cancer than healthy women include:
While these symptoms are more often due to other medical problems, women with ovarian cancer report that the symptoms persist and represent a change from their normal. The frequency and number of these symptoms are also key factors in the diagnosis.
Women who experience these symptoms almost daily for more than a few weeks should see a healthcare provider (preferably a gynecologist) for evaluation.
How is ovarian cancer diagnosed and staged?
The most common reason for a physician to suspect ovarian cancer is if he/she feels a mass during a pelvic examination. When a pelvic mass is found in either a postmenopausal woman, or a girl who has not yet begun menstruating, then they will need to undergo surgery to make the final diagnosis. Chances are very high that a pelvic mass in a young girl or teenager who hasn't begun menstruating is a cancer (usually a germ cell ovarian cancer). However, only 5% of masses felt on pelvic exam in menstruating women are malignancies, and certain characteristics of the mass make it more or less likely to be a cancer. For example, if the mass is solid, irregular or fixed, it is more likely to be a cancer. Often, if you are a menstruating woman, your physician will have the mass further characterized by transvaginal ultrasound. If the mass is small, has pockets (is cystic), is in only one ovary, is freely movable, and has regular contours, then it is unlikely to be a cancer. Masses with these qualities can be followed by clinical exam because there is a good chance that they represent ovarian cysts and will disappear on their own. However, if these masses persist or enlarge, then they need to be surgically explored. Women with a pelvic mass and an increased CA-125 level will go straight to surgery, and women with a pelvic mass and other symptoms suggestive of cancer (like having fluid collect in their abdomen) may also go directly to surgery.
Ovarian cancer is a type of cancer that needs to be diagnosed and staged during a surgery. Often, the cancer is diagnosed and treated during the same procedure. Surgeries for ovarian cancer diagnosis and treatment should be done by a surgeon specialized in gynecologic malignancies. Surgery is done so that samples of the mass and surrounding tissue can be biopsied and analyzed. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. Once the tissue is removed, a doctor called a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, the pathologist will characterize it by what type of tissue it arose from and what subtype of ovarian cancer it is, how abnormal it looks (called the grade), and whether or not it is invading surrounding tissues.
In order to guide treatment and offer some insight into prognosis, ovarian cancer is staged into four different groups at the time of the surgery. Surgeons who specialize in gynecologic malignancies go through a careful inspection and sampling of a woman's pelvis during this procedure, and biopsy specimens are sent to a pathologist for immediate examination while the surgeon is still working. The staging system used for ovarian cancer is called the FIGO system (International Federation of Gynecologists and Obstetricians). The staging system is somewhat complex, but here is a simplified version of it:
Stage I: ovarian cancer confined to one or both ovaries. Cancer cells may also be present on the outside of the ovary or in the abdominal fluid.
Stage II: ovarian cancer that has spread beyond the ovaries, but is confined to the pelvis (can be in the uterus, bladder or rectum).
Stage III: ovarian cancer that has spread within the abdomen or pelvis, which may include the peritoneum (the lining of the abdomen), bowel, surface of the liver and/or lymph nodes
Stage IV: ovarian cancer that has distant spread (metastasis) to other organs
In addition to stage, the tumor grade will also be evaluated. This refers to how abnormal cells appear under a microscope. Low grade (or grade I) tumors appear the most like normal cells, whereas higher grade tumors (grades 3 and 4) appear very abnormal under the microscope. Higher grade tumors may behave more aggressively than low grade tumors.
Generally, the higher the stage, the more serious the cancer. Although surgery is required for accurate staging, your physicians may want to order some other tests to better characterize the mass/masses and look for distant spread. Tests like CT scans or MRIs (like a CT scan but done with magnets) can examine the pelvis and localized lymph nodes. Some patients with bony pain are referred for a bone scan, which is a test using a radioactive tracer to look for metastasis to any of the bones. You may also undergo a colonoscopy, which uses a lighted scope to examine your rectum and colon, or a barium enema in which dye is inserted into your rectum and an x-ray is taken. These tests are to look for spread of the tumor to your colon. Each patient unique, so the specific tests people get will vary; but overall, your doctors want to know as much about your particular tumor as possible so that they can plan the best available treatments.
What are the treatments for ovarian cancer?
Almost all women with ovarian cancer will have some type of surgery in the course of their treatment. The purpose of surgery is first to diagnose and stage the cancer, and then to remove as much of the cancer as possible. In early stage cancers (stage I and II), surgeons can often remove all of the visible cancer. Generally, women with ovarian cancer will have a hysterectomy (removal of the uterus) and bilateral salpingo-ooporectomy (removal of both ovaries and fallopian tubes) as part of their operation. This is because there is always a risk of microscopic disease in both of the ovaries and the uterus. The only circumstance in which a woman may not have this entire operation is if she has a very early stage cancer (IA) that looks favorable under the microscope (grade 1). This is often the case with germ cell ovarian tumors. If a woman's tumor has these characteristics and she desires to maintain the ability to have children, then the surgeons can remove only her diseased ovary and tube. Then after she is done having children, she will need to have her uterus and the other tube and ovary removed. With any other stage or grade of tumor, or in patients finished with childbearing, the entire operation should be performed in order to provide the best possible chance for a cure.
Women who have more advanced disease (stage III or IV) will often have debulking surgeries, which means that their surgeon will attempt to remove as much disease as possible. Data collected in many studies has demonstrated that the more tumor that it debulked, the better the long term outcome for the patient. Sometimes ovarian cancer is diffusely spread throughout the entire pelvis and abdomen, and it can take a surgeon quite some time to get it adequately debulked.
Operations for ovarian cancer should be performed by surgeons who are trained in dealing with gynecologic malignancies because there are special skills and techniques necessary to deal with these tumors. Studies have shown better outcomes and survival for patients operated on by a certified gynecologic oncologist. Sometimes, a patient will have debulking surgery and then later the cancer will come back. It may be useful to debulk the tumor a second time, particularly if it has been at least a year between the initial surgery and the recurrence. In patients with very advanced ovarian cancer, surgery may be used for palliation, meaning that patients are operated on with the intent of easing their pain or symptoms, rather than trying to cure their disease.
Another way that surgery is occasionally used in ovarian cancer is to closely monitor a patient for signs of recurrent disease. This is called a second look surgery, and can be done with an abdominal incision (a laparotomy) or using fiberoptic scopes and long, narrow tools which allow surgeons to operate less invasively (laparoscopically). This used to be a very common procedure, but studies failed to show a strong benefit from performing second look surgeries. Therefore, this procedure should only be done in the context of a clinical trial.
Despite the fact that the tumors are removed during surgery, there is always a risk of recurrence because there may be microscopic cancer cells left that the surgeon cannot remove. In order to decrease a patient's risk of recurrence, they are offered chemotherapy. Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. The vast majority of patients with ovarian cancer should be offered chemotherapy after their surgery. The higher the stage of cancer you have, the more important it is that you receive chemotherapy. Generally, only very early stage cancers (early stage I) that look favorable under the microscope (grade 1 or 2) can be treated with surgery alone. Any woman with a more advanced stage or grade cancer should be offered chemotherapy.
There are many different chemotherapy drugs available, and treatments often combine several drugs to create a regimen. For the treatment of ovarian cancers, chemotherapy is typically given intravenously (into a vein) or directly into the abdomen (intraperitoneal) and is given in a clinic or hospital. With intraperitoneal chemotherapy, the chemotherapy is given directly into the abdomen through a catheter, allowed to "dwell" in the abdomen, coating the area in chemotherapy. After several hours, fluid is drained from the abdomen, releasing the chemotherapy remaining in the abdomen. Several large studies have shown significant survival advantages for women with good surgical debulking followed by intraperitoneal chemotherapy given with or without intravenous chemotherapy. Concerns over quality of life, technical difficulty of the procedure and lack of reimbursement for the procedure have limited the widespread use of IP therapy.
The most common combination currently used for epithelial ovarian cancer is paclitaxel plus either cisplatin or carboplatin (platinum containing drugs), given intravenously. There are other drugs that can be used, like gemcitabine and doxorubicin, and sometimes new combinations are tried if there isn't a response to the original combination. There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle.
Ovarian cancer does not commonly receive radiation therapy in the United States. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for up to 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Radiation therapy is occasionally combined with surgery in patients with stage II tumors with low bulk disease. Radiation can also be used to ease the pain of metastases and/or to stop tumors from bleeding. Generally, doctors try to limit the amount of radiation that your vital organs receive, and don't like to treat large portions of the bowel and pelvis. This makes radiation less useful in ovarian cancer, where disease is often diffusely spread throughout the abdomen and pelvis. A radiation oncologist can answer questions about the utility, process, and side effects of radiation therapy in your particular case.
Once a patient has been treated for ovarian cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up visits, CA-125 levels, pelvic ultrasounds and/or CT scans depending on your case. Your doctors will also perform pelvic examinations during each of your office visits. It is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.
Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today and many exciting new therapies are currently being tested. Some of the areas being studied include new screening tests, vaccine therapies derived from a patient's tumor cells and new chemotherapy and biologic therapies. Talk to your doctor about participating in clinical trials in your area or visit OncoLink's clinical trials matching system to learn about current trials.
This article is meant to give you a better understanding of ovarian cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about ovarian cancer on OncoLink through the related links to the left.
References & Further Reading
American Cancer Society.: Cancer Facts and Figures 2011. Atlanta, Ga: American Cancer Society, 2011 www.cancer.orgBhoola, S. and W. J. Hoskins (2006). Diagnosis and management of epithelial ovarian cancer. Obstet Gynecol 107(6): 1399-410.
Buys, SS et al., (2005) Ovarian cancer screening in the PLCO cancer screening trial: findings from the initial screen of a randomized trial. American Journal of Obstetrics and Gynecology 193(6):2183-2184.
Fader, AN & Rose, PG. Role of surgery in ovarian carcinoma. Journal of Clinical Oncology. 25(20):2873-83, 2007 Jul 10.
FIGO Committee on Gynecologic Oncology.: Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 105 (1): 3-4, 2009.
Gershenson, DM. Management of ovarian germ cell tumors. Journal of Clinical Oncology. 25(20):2938-43, 2007 Jul 10.
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Hamilton, C. A. and J. S. Berek (2006). Intraperitoneal chemotherapy for ovarian cancer. Curr Opin Oncol 18(5): 507-15.
Hensler, M. (2002) Epithelial Ovarian Cancer. Current Treatment Options in Oncology. 3(2):131-41
Martin, VR. Ovarian cancer: an overview of treatment options. Clinical Journal of Oncology Nursing. 11(2):201-7, 2007 Apr.
Morgan, R. J., Jr., R. D. Alvarez, et al. (2006). Ovarian cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 4(9): 912-39.
National Cancer Institute. What You Need To Know About Ovarian Cancer. www.cancer.gov.
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Ovary and primary peritoneal carcinoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 419-23.
Rao, G et al. Intraperitoneal chemotherapy for ovarian cancer: overview and perspective. Journal of Clinical Oncology. 25(20):2867-72, 2007 Jul 10.
Rosenthal, A. N., U. Menon, et al. (2006). Screening for ovarian cancer. Clin Obstet Gynecol 49(3): 433-47.
Rubin, P. and Williams, J.P., (Eds): Clinical Oncology: A Multidisciplinary Approach for Physicians and Students 8th ed. (2001). W.B. Saunders Company, Philadelphia, Pennsylvania.
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Complete FIGO Staging Table
Start by identifying the tumor size (T), presence or absense of lymph node metastatses (N) and distant metastases (M). Combine those evaluations to determine the corresponding stage.