The Menopause Web Reference

Screening, Treatment, and Follow-up brought together epidemiologists; obstetrician/gynecologists; gynecologic, medical, and radiation oncologists; and the public to address the following questions:

What is the actually status of screening and prevention in ovarian cancer?
What is the adequate management of early stage ovarian cancer?
What is the scheduled management of advanced epithelial ovarian cancer?
What is the appropriate follow-up after primary therapy?
What are the directions for future research?

The consensus panel concluded that there is no evidence available yet that the current screening modalities of CA 125 and transvaginal ultrasonography can be effectively used to reduce mortality from ovarian cancer nor that their use will result in decreased rather than increased morbidity and mortality. They recommended that further prospective research be done to evaluate this very important issue. Women with stage IA grade 1 and most IB grade 1 ovarian cancer do not require postoperative adjuvant therapy. Many remaining stage I patients do require chemotherapy. Subsets of stage I must be fully defined and ideal treatment determined. Women with stages II, III, and IV epithelial ovarian cancer (other than low malignant potential tumors) should receive postoperative chemotherapy. Physicians should be encouraged to discuss clinical trial participation with women, and women should be encouraged to participate. All women should have access to accurate and complete information regarding ovarian cancer. Furthermore, there must be no barriers to women's access to qualified specialists, optimal therapy, and protocols.

Why effective screening is impossibleThere is no easy way to evaluate an abnormal test. All you can do is say that your cancer test is positive but that it is probably wrong by a factor of 99 to 1, and maybe you should just forget about it. Or, you could repeat it in several months and pick the best two out of three results. Or, if you wish to pursue it, you will eventually have to remove the ovaries to prove that there is no cancer. Unlike the abnormal Pap test that can easily be evaluated as many times as you wish there is no easy way to evaluate an abnormal Ca-125 or ultrasound test. There is no recognized professional organization that has evaluated this problem that recommends screening. It may be possible someday but not now. Those with a documented familial ovarian cancer syndrome where the lifetime risk of developing ovarian cancer is about 50% are advised to have annual physical examinations and consider an annual pelvic sonogram. Those who have set up ovarian cancer screening programs for women with a family history of ovarian cancer have not reported any substantial benefit. Even if you decided to undergo regular Ca-125 and pelvic sonogram testing, how often should it be done? Every year seems not very adequate for ovarian cancer. How long should it be done? For the next 30 years?

cause: unknown

risk:

lifetime risk of developing ovarian cancer is about 1.7%.
If there is one first degree relative with ovarian cancer then the risk is about 3-5%.
If there are two or more relatives with ovarian cancer then the risk is about 7%. Familial ovarian cancers tend to occur at an early age, before 50 years, and tend to be advanced serous epithelial cancers.

risk factors:

aging
nulliparity
delayed childbearing
affluence

Ovarian cysts

are enlargements of the ovary that appear to be filled with fluid.
may be a simple fluid filled bleb or contain complex internal structures.
The term cyst is used to differentiate them from solid enlargements.
Simple cysts have no internal structures and are less worrisome than those with complex structures or solid components.
A sonogram or ultrasound test can determine if a cyst is simple or complex.
are frequently encountered. Every menstruating woman develops an ovarian cyst each cycle. Sometimes the ovary does not ovulate and the follicle cyst persists. It will continue to enlarge and can become as big as a baseball. Eventually it will break and the woman may not even be aware that this has happened.

Could the cyst be a cancer? If:

a sonogram shows it to be a simple cyst without any internal structure.
it is only on one side.
t is less than 4-5 inches in diameter.
it occurs in an ovulating woman or an early pregnant woman.
there are no associated findings such as nodules or fluid in the pelvis.
there are no major symptoms of pain.

Then wait.
Schedule a reexamination for 4 weeks. If it is gone or getting smaller then it was a functional cyst: either a follicle cyst or a corpus luteum cyst. Nothing more needs to be done. If it persists then a diagnosis must be arrived at surgically.
You have to remember that patients on birth control pills should not develop functional cysts. (The function of the pill is to suppress ovulation, although some women ovulate on their pills). Premenarchal and postmenopausal women should not develop functional cysts. Women in these groups with a cyst as well as those with a complex or a solid cyst will have to be evaluated surgically. This is the only way to make sure that the cyst is or is not a cancer.

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Uterine Cancer: Screening, Treatment, and Follow-Up

Author:
MD. William M. Rich
Last Review: 21/02/2003

Types of uterine cancers Each of these three parts gives rise to cancers. The smooth muscle cancers are called leiomyosarcomas(ly o myo sarcomas). There is also a benign tumor of smooth muscle called a leiomyoma. The common name for this benign tumor is myoma or fibroid. The endometrial stroma gives rise to a variety of cancers classified as sarcoma. The glandular lining gives rise to adenocarcinomas. Ninety-five percent, of uterine cancers are adenocarcinomas arising from the lining. The term uterine cancer usually refers to these adenocarcinomas.
Adenocarcinomas are graded. Grade I means well differentiated, that is, they are easily identified as originating from the glandular tissue and have easily identifiable glandular structures. Grade III means poorly differentiated with loss of the glandular structures. They are just solid cancer. Grade II cancers are intermediate in appearance. Grade I cancers are expected to behave the best, Grade III cancers the worst.
There are premalignant changes that can occur in the lining of the uterus. These changes are almost always due to excessive stimulation of the endometrial glands by an excess of estrogen or a prolonged estrogen influence. They can occur in younger women who do not ovulate regularly as well as in older women who are obese.
These changes are called endometrial hyperplasias. They are diagnosed usually by endometrial biopsy. They are not cancers but are often best treated by hysterectomy. They can also be treated by high dose progesterone therapy. If they occur in a young woman she will probably also be relatively infertile due to irregular or infrequent ovulation. In these cases, the treatment is by drugs that cause ovulation. If you ovulate you will no longer have unopposed estrogen stimulation because you now have the progesterone phase to the menstrual cycle. If you get pregnant then that will reverse the hyperplasia also. For most women the best treatment will probably be hysterectomy.
Papillary serous adenocarcinomas and clear cell adenocarcinomas are a subtype of uterine adenocarcinomas. They are different because of their increased potential to spread throughout the abdomen. In this they sometimes behave like an ovarian cancer. The diagnosis and staging is the same as for the more usual endometrial cancer. The best treatment has yet to be demonstrated. There is a good reason to consider treating the entire abdomen, but there is no good way to do it. Whole abdominal radiation can be done, but it can have a lot of side effects. This is a situation where several opinions should be obtained.

Risk factors for uterine adenocarcinomaAge is the most important risk factor. This is a cancer of postmenopausal and perimenopausal women. There is also a well-recognized association with estrogen. Estrogen is a hormone produced by the ovary. The ovary does several things under the direction of the pituitary gland in the head. First, the pituitary directs the ovary to start maturing an egg. It does this by sending the ovary the pituitary hormone Follicle Stimulating Hormone (FSH). The ovary develops a small cyst or follicle about one half inch in size within which is the egg. During the maturation process the ovary is making estrogen. One of the effects of the estrogen is to stimulate the endometrial glands to grow and proliferate. Then the pituitary tells the ovary to ovulate which means break the follicle and release the egg. The pituitary hormone for this is called Luteinizing Hormone (LH).
The egg is ejected and floats into the fallopian tube. The remnant of the follicle, under the influence of LH starts to make progesterone. Progesterone converts the lining of the uterus to accept the pregnancy. If pregnancy does not occur that cycle then the ovary stops making progesterone. When the progesterone level falls the support for the uterine lining is lost and it falls off. This is the menstrual period. Then, it all starts over again: estrogen, ovulation, progesterone, and the period.
If the woman has a problem that prevents ovulation then the ovary will continue to make estrogen. This will result in prolonged unopposed estrogen stimulation to the endometrial glands and this will increase the risk for cancer of these glands. Postmenopausal women who are taking estrogen also will have an unopposed estrogen stimulation to the uterine glands and be at increased risk for developing an adenocarcinoma of the uterus. This is why a progestin such as Provera is also prescribed. Postmenopausal women who are obese have an increased level of estrogen because the adipose tissue converts other normal body chemicals into estrogen, so they are also at increased risk. Women who take Tamoxifen for breast cancer are also thought to be at increased risk because Tamoxifen is an estrogen. These increased risks are on the order of about 5-12 times the normal risk.
Conditions that increase the progesterone influence on the uterus decrease the risk for adenocarcinoma of the endometrium. Pregnancy is a time of increased progesterone levels, so women who have been pregnant most of their lives are at decreased risk. Women who have taken birth control pills for a long time are at decreased risk. Birth control pills contain both an estrogen and a progestin, but the net effect is that of the progestin. Prolonged progestin influence on the endometrium produces a thinning and atrophy of the glands which is just the opposite of the effects of estrogen. There are other minor risk factors but almost all are mediated through an estrogen progestin link.

Syntomps of uterine cancerThe most frequent symptom of cancer of the uterus is abnormal bleeding. In postmenopausal women any bleeding is considered cancer of the uterus until proven not to be. The only way to prove that there is or is not a cancer inside the uterus is by removing some of the uterine lining as a biopsy. This can often be done easily in the office without any anesthesia, or it can be done in the operating room with an anesthetic. The procedure is called a D&C, dilatation of the cervix and curettage of the uterine lining. Sometimes a scope can be inserted through the cervix into the uterus and the lining visualized and biopsied directly. This is called hysteroscopy.
Whatever the procedure, you must be convinced that the bleeding is not due to a cancer inside the uterus. The Pap test cannot assess the inside of the uterus and is of no value. A trial of hormones is inappropriate. Any postmenopausal bleeding must be taken seriously and evaluated. Occasionally a sonogram or ultrasound test that assesses the thickness of the endometrial lining can be helpful, especially in an elderly debilitated woman who cannot be easily biopsied and who is also an anesthetic risk. If the lining can be seen and measures less than 5mm, then there is unlikely to be a cancer present.
The problem with postmenopausal hormone replacement is that it often causes some irregular bleeding which may require a biopsy. If the hormones are taken on a cyclic basis where there are several days each month when bleeding may occur and if the bleeding is light and occurs on those days then biopsy need not be done. If it occurs at any other time in the cycle then a biopsy should be done. If the hormones are both being taken on a continuous basis each day and bleeding occurs then a biopsy should be performed.

Screening for uterine cancer There are no recommendations for screening for cancers of the uterus. The only screening procedure is an endometrial biopsy. Some have suggested that women who are taking replacement estrogen only, without the progesterone, should have an annual biopsy. Also women on Tamoxifen should probably be biopsied annually. The Pap test is inadequate for cancers inside the uterus although occasionally this cancer will be found on a Pap test. If the Pap test shows endometrial cells then this is abnormal and should be evaluated with an endometrial biopsy.

DiagnosisCancers of the uterus are diagnosed by endometrial biopsy, D&C, hysteroscopy and sometimes only after hysterectomy. The important point is that any postmenopausal bleeding must be considered a cancer of the uterus until proven otherwise. It is fortunate that uterine cancers bleed early so symptoms are early and if the bleeding is not ignored, diagnosis is early. Three-fourths of all uterine cancers are diagnosed at an early stage. Of these about three-fourths are of favorable grade. This is why the number of deaths from uterine cancer is low even though it is the most frequently diagnosed gynecologic cancer.

Staging of uterine cancerCancers of the uterus are staged by surgical exploration with removal of the uterus, tubes and ovaries. In addition, an assessment of the pelvic and aortic lymph nodes is done.

**Surgical Stages of Cancer of the Uterus**
Stage I		Cancer limited to the lining of the uterus
	IA	No invasion into the uterine wall
	IB	Invasion into less than one half of the uterine wall
	IC	Invasion into more than one half the uterine wall
Stage II		Extends into the cervix
	IIA	Extends only superficially along the endocervix
	IIB	Extends deep into the cervix
Stage III		Cancer has spread beyond the uterus
	IIIA	Cancer involves the tubes or ovaries
	IIIB	Spread to the vagina
	IIIC	Spread to the pelvic or aortic lymph nodes
Stage IV		Distant metastases
	IVA	Is inside the bladder or rectum
	IVB	Throughout the abdomen or other distant sites

In addition, these cancers are also graded; Grade I, II and III. To determine the correct stage the uterus, tubes and ovaries will have to be removed as well as sampling the pelvic and aortic lymph nodes. An early stage is assigned by excluding the more advanced stage. Some cases that are obviously in an advanced stage by physical examination will not benefit from surgery and can be treated without operative staging.

TreatmentTreatment of uterine cancers is usually by a combination of surgery and radiation. Those that are at an early stage will be operated first with removal of the uterus, tubes and ovaries, to confirm the stage. If there is only limited invasion into the wall of the uterus and the grade is good, i.e. grade I or II, then the surgery will be sufficient and no radiation will be recommended. If of higher stage and grade then radiation to the pelvis will often be advised. Some doctors prefer to give radiation prior to surgery but that is becoming less prevalent. Advanced stages are treated by radiation if possible, or chemotherapy. Fortunately, progesterone, which has few side effects, is a good chemotherapeutic. Other types of chemotherapy have limited effectiveness but are often used and can give an initially good response.
Most patients will be in an early stage when diagnosed and there will be several options for treatment. Often these are elderly women who may have other medical problems. Nevertheless, a maximum effort should be taken to bring these patients to surgery since the cure rate drops by 20% if a hysterectomy is not performed. With no other gynecologic cancer is treatment so individualized as with early stage endometrial cancer.

PrognosisSince most patients are diagnosed at an early stage and with an optimal grade, most patients are cured. Nevertheless, stage for stage it is just as bad a cancer as any other. Most recurrences will occur in the first two years. If none have occurred by five years the patient is considered cured.

**Five Years Survival for Uterine Adenocarcinoma**
Stage I	80%
Stage II	65%
Stage III	30%
Stage IV	10%

Stage IA, grade I, cancers have a five year survival in excess of 95%. The prognosis depends on the substage and the grade.

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