In the 1980’s, a large study was performed to identify the pathologic findings that truly influenced the risk of recurrence and the overall survival in endometrial cancer. Some easily determined uterine and extra-uterine factors were identified including the cell type, tumor grade, depth of invasion of the uterine muscle (myometrial invasion), metastases to the pelvic and para-aortic lymph nodes, and metastases to the fallopian tubes and ovaries. These findings ushered in the era of “surgical staging” of endometrial cancer, which had previously been staged by physical examination alone. Complete surgical staging requires a careful exploration of the abdomen and pelvis, a total hysterectomy, removal of both tubes and ovaries, and selective biopsy of the pelvic and para-aortic lymph nodes.

At the time, the only available mode of surgery to accomplish this staging was traditional open surgery (laparotomy). However, in the 1990’s improvements in laparoscopic equipment made it feasible to perform comprehensive staging without the large incision required for a laparotomy. Laparoscopic procedures (sometimes referred to as “keyhole” surgery) allow the surgeon to access the abdomen and pelvis through small incisions (usually 5-10 mm in diameter each). Because the uterus, cervix, tubes and ovaries can be removed through the vagina, there is no need for a larger incision. The first minimally invasive surgery to comprehensively stage endometrial cancer was a laparoscopic-assisted vaginal hysterectomy with removal of the tubes and ovaries and laparoscopic nodal sampling. Techniques for total laparoscopic hysterectomy and staging quickly followed. Presently, approximately 60% of endometrial cancers in the United States are managed via minimally invasive surgery, many utilizing robotic-assisted laparoscopy. Laparoscopy has been proven superior to laparotomy with regard to postoperative pain and recovery time in a number of clinical scenarios including endometrial cancer staging. The three to four day hospital stay following a laparotomy is typically reduced to one postoperative day for women that undergo minimally invasive staging. More importantly, the typical 6 week home recovery for laparotomy is routinely shortened to approximately 2 weeks for laparoscopy. Many studies have proven the equivalence of laparotomy and laparoscopy with regard to the risk of recurrence and survival in patients with endometrial cancer.

Removal of both tubes and ovaries is recommended for comprehensive staging of endometrial cancer for two reasons. The first reason is the concern for microscopic spread of tumor to the tubes or ovaries that would go undetected if the organs were left in place. The second concern is the potential stimulation of microscopic residual cancer cells by the continued estrogen production if the ovaries are retained. These risks are theoretical and prior studies suggest that both are low. One concern, however, is that the risk of a separate ovarian cancer at the time of the endometrial cancer diagnosis (termed a "synchronous ovarian tumor") is higher in younger women and can be as high as 30%. There is a growing literature suggesting the safety of retaining the ovaries in young women with low-grade endometrial cancers with minimal invasion of the uterine muscle, although further studies are needed to confirm this. This is an important finding as the incidence of endometrial cancer is increasing and approximately 10-15% will be diagnosed in premenopausal women.

Uterine cancer includes cancer of the muscle, called sarcoma and cancer of the inside lining called endometrial cancer. The most common form is endometrial cancer. In fact, it is the most common gynecological malignancy in the United States.

When endometrial cancer is suspected, an office endometrial biopsy should be performed. You may have some cramping but it’s reasonable. I’ve had the procedure done and immediately returned to work that day.

After endometrial cancer is diagnosed the next step is surgical treatment. The goal is to have minimally invasive surgery. Robot-assisted or laparoscopic surgery has replaced the open surgical approach to endometrial cancer. However, there are those unusual cases when the only option is an open surgery.

Depending of the stage of endometrial cancer one may require:
- no radiation
- internal radiation only
- external radiation and internal radiation

It would be unusual to recommend external radiation without internal radiation even though exceptions may occur. Staging of endometrial cancer is a surgical staging therefore everyone undergoes surgery first. During the surgery uterus and cervix is removed and the top of the vagina is sutured off. The gynecological oncologist also removes some lymph nodes from the pelvic area so the pathologist can examine them under microscope and see whether they have been involved by cancer cells or not. After the pathologist examines the entire surgical specimen and finalizes the staging of cancer a radiation oncologist would be consulted. Based on the given information, the radiation oncologist has to make two major educated estimates:
- What is the risk of a recurrence at the top of vagina (i.e. vaginal cuff recurrence)
- What is the risk of a pelvic recurrence (or a pelvic lymph node recurrence)

If the risk of vaginal cuff recurrence is more than 15% internal radiation or vaginal cuff boost is indicated. If the risk of pelvic recurrence is higher than 15% external radiation to pelvis is indicated. If the risk of recurrence at both of these areas are higher than 15% a combination of these treatments are indicated. If either of these risks are less than 15% no radiation is indicated. Vaginal cuff boost or internal radiation would be delivered by using vaginal cylinder and High Dose Rate (HDR) machine.

The exception to all of the the above is a patient who can not undergo surgery. In that scenario, radiation therapy would become the primary treatment. A combination of internal and external radiation would be indicated. For internal radiation, a double tandem intrauterine catheter and High Dose Rate (HDR) machine would be utilized. In the absence of HDR machine, one may use Hayman Capsule catheters and Low Dose Rate Brachytherapy technique.

When endometrial cancer is limited to the body of uterus and has not spread to cervix, it is called stage I. Stage I endometrial cancer is subdivided into stage IA and IB. Stage IA applies to when the cancer is either limited to the endometrium (inner lining of uterus) or has invaded less than 50% of myometrium (the middle layer of uterus). When more that 50% of myometrium is invaded endometrial cancer is upstaged to stage IB. In addition to stage of cancer, grade of tumor is taken into account to determine whether radiation is necessary or not. Depending on how aggressive a tumor looks under microscope a pathologist would categorize it as grade 1, 2 or 3.

A grade 3 tumor which has invaded more than 50% of myometrium has a much higher risk of recurrence than a grade 1 tumor only involving endometrium. The higher the risk of recurrence the more likely radiation would be recommended.

There are other pathological factors such as lymphovascular invasion, size of tumor,its location, family history and age of the patient which are taken into consideration to determine need for radiation for each patient on an individualized basis. That is why multidisciplinary conferences/tumor boards are the best venue to make joint recommendations for review of pathology slides and pertinent clinical information.

This is an area of active work and some promising targets have been identified. Drugs that block the vascular pathways (ie, anti-angiogenic agents) look promising (such as bevacizumab and brivanib) as do drugs that block specific pathways like the mTOR pathway (such as with everolimus). We are exploring both administration of single agents alone and when combined with traditional chemotherapy as ways to use these drugs in endometrial cancer. However, these trials are still being performed and none of these drugs are ready to be used outside of a clinical trial.

The role of routine lymph node sampling in endometrial cancer care remains hotly debated. As I mentioned previously, the determinants of recurrence and survival in endometrial cancer include the tumor grade and depth of invasion of the uterine muscle (myometrium). These factors also predict the risk of spread to the pelvic and para-aortic lymph nodes. For example, a woman with a grade I endometrial cancer with invasion of only the inner 1/3 of the myometrium carries a 3% risk of a pelvic node metastases. Comparatively, a woman with a grade 3 tumor and myometrial invasion to the outer third carries a 30% risk of pelvic node metastases. These risks, however, are base on postoperative pathology findings and not an intra-operative assessment of tumor grade and myometrial invasion. As in any medical decision, the risk of missing a lymph node metastasis must be weighed against the risks of lymph node sampling, which include bleeding and postoperative lymphedema (swelling of the lower extremities).

There are three schools of thought with regard to the role of lymph node sampling in endometrial cancer. Some surgeons perform routine sampling of the pelvic and paraaortic lymph nodes for all patients, others biopsy only suspicious lymph nodes found at surgery or identified on preoperative imaging studies, while the remaining surgeons utilize some form of pre and intra-operative risk assessment to determine which patients are at risk for nodal spread and should undergo the procedure. Presently, I perform some level of lymph node sampling on all patients that are safe surgical candidates because I believe that lymph node data is useful for determining the need for postoperative therapy and I question the ability to accurately predict the risk of nodal spread pre or intra-operatively. The available literature has not brought clarity to this debate with some studies suggesting a benefit to lymph node sampling and others showing no benefit.

Presently there are no standard recommendations for follow-up of patients who have completed primary treatment for endometrial cancer and are in a clinical remission. No specific intervention (ie blood tests, CT scans, chest x rays) has been shown to affect overall survival in this patient population and because of this there is wide variation in practice. Women with a history of endometrial cancer remain at risk for local, regional, and distant recurrences and an ideal follow up plan should take each possibility into account. The level of risk, however, is determined by their tumor cell type and the stage of their disease following comprehensive surgical staging.

The tools frequently used to screen women with no symptoms of recurrence include routine pelvic examinations with or without vaginal Pap smears, pelvic and abdominal imaging tests, chest x ray, and the CA 125 blood test. It is my practice to see patients for scheduled visits every three months for the first two post-treatment years and then semi-annually thereafter. During these scheduled visits patients undergo careful full physical examination and a Pap smear of the upper vagina. I use CT scans of the abdomen and pelvis and chest x ray to rule out distant recurrence in patients who offer new complaints suggestive of recurrence. In the absence of symptoms, my use of CT scans and chest x ray is restricted to the minority of patients with advanced stage disease or those at increased risk of recurrence by nature of an aggressive tumor cell type.