Endometrial cancer is the MOSt common malignancy of the female genital tract. It usually shows itself early by irregular, persistent bleeding. IT progresses through a series of changes from normal to hyperplasia to cancer over time, thus allowing earlier diagnosis, intervention, and overall a good prognosis.
Average age is 60 y/o. The most common cause is persistent ,prolonged estrogen exposure with out adequate progesterone opposition. It begins as cells slowly change from normal , becoming hyperplastic (Too thick- too many cells), less organized (complex hyperplasia), more and more atypical cells, and ultimately cancerous. Because each gland reacts to the estrogen stimulation at differing rates, there may be several levels of abnormality in the same uterus at the same time ( i.e.- normal cells, next to complex hyperplasia, with some areas of early carcinoma).90% of endometrial cancers are endometrioid cell types, which are lower grade and have a good prognosis.About 10% are more papillary serous cell types which behave much more aggressively and are the cause of most recurrences. Clear cell and MMT are rare types with extremely poor prognosis.
Let’s talk about risk factors. The endometrium is normally under the influence of estrogen from menarche to menopause, predominantly in the follicular phase (proliferative phase) or first half of the menstrual cycle. The more exposure to estrogen, the more proliferation of the endometrium occurs. When the uterus never gets a break from this stimulation (infertility, nulliparity) endometrial cancer is more likely to occur.With increased BMI comes increased estrogen stimulation due to the aromatization of circulating precursors into estrogens in the fat cells. Thus, higher incidence of endometrial ca. If that chronically elevated estrogen level causes infrequent / inconsistent ovulation by negative Pituitary feedback, menses become irregular, endometrial build-up is more likely and the progression from normal> hyperplasia> cancer begins.All of this takes time. It doesn’t happen in a few cycles. So a woman who started menses early, finished late, had a more years of irreg menses is more likely to develop endo ca.Genetics- There is also an increased risk for families with nonpolyposis colorectal cancer. Actually a 40-60% lifetime risk of endometrial Ca for women in these families.
What risk factors did you hear her name? One that she alluded to is her weight. She is 5 ft tall and at the time of diagnosis was 296LB. It isn’t unusual for women who are self-conscious of their weight to avoid seeking medical care. It’s also not unusual for women to think “This is menopause. It will surely go away soon.” Busy with life, time gets away from them and before they know it, a few months of irreg bldg with occ gushes has turned into too many month and things have progressed.
There is no screening test. At routine physical or yearly Gyn exam, there will be no physical findings. It is the bleeding pattern that you must listen for. Is this a normal time in her life to to bldg? (Certainly if she had gone a full year with no periods, she is menopausal and shouldn’t be bldg again.) Is it a normal pattern? A normal amount? Any time after aged 35-40, irregular bldg should alert you to the possibility of endometrial cancer. The more risk factors the patient has, the more you should be concerned.Once your index of suspicion has been raised, you need TISSUE to know for sure.Let’s have a word about US. US will tell you shape and size of the uterus. OVERALL,this isn’t helpful in diagnosis. HOWEVER, in a menopausal woman who doesn’t have estrogen stimulating her endometrium, the endometrium should be very thin. The endometrial thickness CAN be measured on US> We know that cancer has almost never been found in an endometrium measuri ng less than or equal to 4mm . This is the one use of US in this disease. If an elderly woman comes in bleeding and US reveal s endometrial stripe <= 4mm, she doesn’t need a biopsy or treatment, just f/u.
How did she describe her bldg pattern? Is this a normal cycle? What risk factors did she have? What about age? Would you expect at age 58 that she would still be bldg? Part of the confusion for Mrs T arose from the fact that she kept waiting for menopausal symptoms. Since she never hot flashed and never had an extended period with no bldg, it took longer for her to realize something was amiss.
A packet is available with an aspiration biopsy device used to get a sample of endometrial cells. In the packet are directions for a short lab to practice using it and a YouTube site showing a 2 minute video to watch before trying. This can be done in the office. Most of the time, the pathology on your sample with be consistent with what a full pathology specimen would reveal, thus making it a good office approach to diagnosis.However, there are times where the cervix is too stenosed to get through,or where the pathologist tells you that not enough specimen was obtained to give you a reliable answer as to whether or not there is cancer. Then you must proceed or refer for D&C to get a sample. This is still a diagnostic procedure NOT a treatment. Even with adequate tissue on D&C, invasive lesions can be missed. The only complete diagnosis can be gotten when the entire uterus in “in the pan”. Therefore , if your biopsy is negative but the patient continues to bleed, keep looking!
Let ‘s talk about US. Though no kind of imaging will give a tissue diagnosis, US does have a place in the diagnosis of endometrial ca. With US the thickness of the endometrium can be accurately measured. This is used in infertility to see if the lining is adequately prepared for implantation. If the endometrial width is within normal limits, an endometrial mass such as a polyp or fibroid isn’t likely. AND in a postmenopausal female we know that an endometrial stripe (thickness) of less than or equal to 4mm is extremely unlikely to harbor endometrial cancer. Therefore, an US report showing <= 4mm of endometrium in a menopausal woman allows us to safely watch and not biopsy.
Endometrial cancer starts a specific area – usually the glands of the endometrium. It grows locally, working it’s way through the endometrium. The further it gets through the endometrium, the increased likelihood disease extending to the ovaries, getting into the pelvic lymph nodes and then to the the periaortic nodes. This readily demonstrated by going to the above web site under the diagnosis and staging section then scrolling down to the pictures of stages. Keep clicking and you’ll watch the progression. Knowing how it behaves allows adequate treatment and appropriate follow-up.
If your pathology shows that the tissues is not fully cancerous yet (hyperplasia, complex hyperplasia, even atypical hyperplasia if fertility is to be retained) > progestational agents can be used to reverse the process. Close follow-up of the tissue must be maintained. For endometrial cancer, treatment is based on staging. Staging is surgical. How far does it go through the endometrium? Is it in pelvic lymph nodes? Periaortic nodes? If the disease is Stage 1 (based on surgical staging), post-operative radiation doesn’t improve survival.For any with disease beyond stage I, radiation therapy is the next step.
Prognosis for the endometrioid cell type ( 90% - 95% of all endometrial Ca) is good. She will continue to live after adequate treatment , to have to deal with the other issues of obesity and prolonged estrogen stimulation. The earlier it’s found, the easier to treat (Remember stage 1 is completely treated after the surgical staging hysterectomy!) Follow-up is fairly simple – several visits to the Gyn Oncologist for pelvic exams only.Rare cell types are much more likely to recur and are less responsive to radiation therapy from the onset.
In review, to find and treat endometrial cancer, you must listen for the clues. Is this patient at risk? Does she have prolonged estrogen exposure either endogenous or exogenous? Has she described bleeding to you that isn’t normal? Has it gone on long enough (is she old enough) to warrant concern for the status of her endometrium. Remember: there is no way other way to screen for this. Nothing for look for on routine exam. No xrays or labs to order. Endometrial biospy is the beginning of diagnosis for what can be a very successful cancer story.
CANCER IN WOMEN
2009 Estimated US Cancer Cases* Men Women 766,130 713,220Prostate 25% 27% BreastLung & bronchus 15% 14% Lung & bronchusColon & rectum 10% 10% Colon & rectumUrinary bladder 7% 6% Uterine corpusMelanoma of skin 5% 4% Non-Hodgkin lymphomaNon-Hodgkin 5% lymphoma 4% Melanoma of skinKidney & renal pelvis 5% 4% ThyroidLeukemia 3% 3% Kidney & renal pelvisOral cavity 3% 3% OvaryPancreas 3% 3% PancreasAll Other Sites 19% 22% All Other Sites*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2009.
2009 Estimated US Cancer Deaths* Men 26% Lung & bronchusLung & bronchus 30% 292,540 15% BreastProstate 9% 9% Colon & rectumColon & rectum 9% 6% PancreasPancreas 6% 5% OvaryLeukemia 4% 4% Non-HodgkinLiver & intrahepatic 4% lymphoma bile duct 3%Esophagus 4% 3% Uterine corpusUrinary bladder 3% 2% Liver & intrahepaticNon-Hodgkin 3% bile duct lymphoma Women 2% Brain/ONS & 269,800Kidney & renal pelvis 3% 25% All other sitesAll other sites 25%ONS=Other nervous system.Source: American Cancer Society, 2009.
Cancer Death Rates* Among Women, US,1930-2005100 Rate Per 100,000 80 60 Lung & bronchus 40 Uterus Breast Colon & rectum 20 Stomach Ovary Pancreas 0 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 *Age-adjusted to the 2000 US standard population. Source: US Mortality Data 1960-2005, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2008.
Symptoms/ Screening Bloating Constipation Abdominal discomfort Indigestion Urinary incontinence Urinary frequency Fatigue Anything that doesn’t feel right in the abdomen
How does it behave? Cell types 85% epithelial Benign Low malignant potential MalignantLocalLymphaticExfoliates
Treatment Bad News Even more…. 2/3 have advanced May develop resistance disease when diagnosed to the chemo before 1st Tx: Surgical debulking tx over (cytoreduction) More bad news Death Chemotherapy next With advanced disease Bowel obstruction only 50 % remission malnutrition after chemo Ureteral obstruction