Diagnosis and Treatment of Endometrial Cancer

Emma Rossi, MD

Endometrial tumors form in the tissue that lines the uterus. The National Cancer Institute estimates that about 52,000 new cases of endometrial cancer are diagnosed each year, and about 8,600 women die each year of the disease. Today, we are speaking with Emma Rossi, MD, assistant professor of obstetrics and gynecology at Indiana University in Indianapolis, about the diagnosis and treatment of endometrial cancer.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Dr. Rossi, is endometrial cancer a tumor type that has distinct symptoms?

Dr. Rossi: It is. Most endometrial cancer, and by that I mean 90% of women with endometrial cancer, presents with uterine bleeding that is abnormal. For a woman who has stopped having her period, usually for a woman of 50 or over, that means she has new onset bleeding that she has not had for many years, and if it occurs in younger women, it usually means that their regular periods are usually much more abnormal, either heavier or they may be bleeding in between periods. This is the classic way that the cancer is typically diagnosed initially, with abnormal uterine bleeding or new emergent bleeding after menopause. Very, very occasionally it is diagnosed in a routine Pap smear, but Pap smears are designed to detect cervical cancer and do not reliably detect uterine or endometrial cancer, although occasionally the shed uterine cancer cells can show up in the Pap smear.

Cancer Network: Are there regular screening methods specifically for endometrial cancer? And are most women diagnosed with early-stage disease?

Dr. Rossi: Yes. About 70% of women are diagnosed with cancer confined to the uterus, which is stage I cancer and that is associated with good prognosis. The reason that most women are diagnosed at an early stage is because this type of cancer really does present with symptoms early in its course, and a woman who is clued into these symptoms typically communicates this with her doctor. There are no specific screening tests for endometrial cancer, not like a Pap smear for cervical cancer. But what we teach women, as clinicians, is to understand their bodies and their normal symptoms, particularly abnormal bleeding in a premenopausal woman, and to seek a doctor’s advice if there is a new pattern of bleeding-bleeding in between periods and an onset of heavier period bleeding. We also teach women to let their doctors know if they have bleeding postmenopause. There are some tests that have been looked at, such as using ultrasounds, but these would have to be internal ultrasounds, or doing biopsies of the endometrium, but these are both fairly invasive tests that we don’t think will be helpful for the general population. We only reserve these types of tests for women who are really at high risk for developing uterine or endometrial cancer.

Cancer Network: Are there any known genetic and lifestyle risk factors that put women at risk for endometrial cancer?

Dr. Rossi: Certainly. The number one risk factor for uterine or endometrial cancer is obesity. And that’s an increasing problem across the United States and the Western world in general. As a result, we are seeing increasing rates of endometrial cancer incidence. Obesity can actually cause the uterine cancer because it is associated with changes in a woman’s hormones. The fat cells actually make hormonal material that stimulates the endometrial lining and can turn those cells into cancerous cells. Other medical conditions that are in some way associated with obesity, but not always, are diabetes and high blood pressure, which may cause an increased risk of endometrial cancer. There are some medications that increase a woman’s risk, such as estrogen therapy without progesterone therapy, which has a balancing-out effect on the estrogen therapy. Estrogen therapy alone increases risk. Medications such as tamoxifen, which is a common medication for breast cancer treatment, and prophylaxis treatment, which has a stimulatory effect on the endometrium, also result in an increased risk for endometrial cancer.

The number one genetic or inherited risk for endometrial cancer is a condition called Lynch syndrome. About 10% to 20% of women with endometrial cancer will have this cancer as a result of being born with a predisposition for cancer. This is Lynch syndrome, which is a condition in both men and women that causes an increased risk for colon cancer in men and for endometrial cancer and colon cancer in women, as well as some other cancers, such as breast, ovarian, and urinary tract cancers. Those women are not only likely to be diagnosed at a younger age in general, but often also are at a significant risk of being diagnosed with another cancer in another organ type. When we see women who have developed endometrial cancer at a very young age and with a strong family history of colon, endometrial, breast, or ovarian cancer, we begin to be concerned about the presence of Lynch syndrome in that family. We often test them for it, and then know that we have to screen them closely for other cancers.

Cancer Network: What are the current methods for diagnosing endometrial cancer, and can you talk about the role of sentinel node biopsy?

Dr. Rossi: Right now endometrial cancer is diagnosed typically with a biopsy of the uterine lining, which usually occurs in a clinical office. A physician will perform the exam, which is very much like having a Pap smear. They will place a very thin tube into the uterine cavity and obtain some cells, which will include uterine lining cells that are then examined in a laboratory. That same test can also be done in an operating room if the woman cannot tolerate the office exam. Once endometrial cancer is diagnosed, the cancer needs to be staged and determined whether it has spread to other organs. The way we do that is less by using scans (although in some patients we will use CT scans to look to see if there is any obvious cancer spread), the best and recommended way to diagnose spreading of the cancer is in the operating room. For the surgery, we perform a complete hysterectomy, removing the uterus, tubes, cervix, and ovaries, and evaluate the lymph nodes to which endometrial or uterine cancer commonly spread to. The lymph node assessment used to be done predominantly with a big open incision in the abdomen, which is associated with some pretty significant post-operative complication rates because most patients with endometrial cancer are obese, and obesity in combination with a big open surgery is particularly risky for development of complications, especially wound complications.

So, what has been developed over time are a series of minimally invasive surgical techniques that have been shown in large randomized studies to be equivalent to the big open operation in terms of being able to remove the relevant tissues and diagnose cancer spread, but have much fewer surgical complications-particularly, after the surgery, better and faster recovery, improved quality of life, less infection, and less blood loss. We do these surgeries through small keyhole incisions or laproscopically with or without robotic assistance-these are the two most common ways in the United States to do these surgeries. And patients usually stay overnight in the hospital and recover well. We are decreasing the toxicity of the surgery, and we are also scaling down on removal of tissues. Traditionally, we would remove all the lymphatic tissue in the body that potentially might drain the cancer and look at these under the microscope, knowing that at least 70% of patients will have negative results.

Now, we try to stratify patients who are most at risk for lymph node disease and only expose those patients to a lymph node dissection, or alternatively, to a technique called a sentinel node biopsy. This is where we inject a dye into the cervix or the uterus after the patient has received anesthesia so they do not feel the injection, and then during the operation we can see the flow of the lymph fluid from the uterus, from the cancer, to where the cancer cells would have gone to if it had spread to the lymph nodes. We can see which individual lymph nodes are most likely to be involved in cancer and remove those individually, rather than removing all of the lymph node tissue that potentially could be involved in the cancer drain. This is a technique that is now routinely used in early-stage breast cancer and is now being explored for uterine and cervical cancers. And from preliminary studies, it is looking to be a very accurate technique in diagnosing cancer spread without missing anything important, and it has the potential to reduce the toxicities and complications associated with surgery.

Cancer Network: Lastly, what is the standard course of intervention for women with early-stage endometrial cancer?

Dr. Rossi: The standard course would be a diagnosis made through a biopsy, typically in the clinical office. At that point, the clinician may decide to do some preoperative evaluation. Depending on the patient and the biopsy results, this may be a CT scan or blood work. Ultimately, if the cancer looks like it is confined to the uterus, that patient usually needs surgery to confirm the diagnosis and remove the organ that has cancer. The patient is scheduled for an operation, which is now typically a minimally invasive hysterectomy and lymph node evaluation.

Cancer Network: Thank you so much for joining us today, Dr. Rossi.

Dr. Rossi: You are very welcome. Thank you.