Treatment Choices for Endometrial Cancer, by Stage

The stage (extent) of endometrial cancer is the most important factor in choosing treatment. But other factors can also affect your treatment options, including the type of cancer, your age and overall health, and whether you want to be able to have children. Tests done on the cancer cells are also used to find out if certain treatments, like hormone, immunotherapy, and targeted therapy, might work.

Surgery is the first treatment for almost everyone with endometrial cancer. The operation includes removing the uterus, fallopian tubes, and ovaries. (This is called a total hysterectomy bilateral salpingo-oophorectomy or TH/BSO). Lymph nodes from the pelvis and around the aorta may also be removed (a pelvic and para-aortic lymph node dissection [LND] or sampling) and tested for cancer spread. Pelvic washings may be done, too. The tissues removed at surgery are tested to see how far the cancer has spread (staging). Depending on the stage of the cancer, other treatments, such as radiation and/or chemotherapy may be recommended.

For some who still want to be able to get pregnant, surgery may be put off for a time and other treatments tried instead.

If a patient isn't well enough to have surgery, other treatments, like radiation, will be used.

Treating stage I endometrial cancers

Stage I is either only in the uterus or is a non-aggressive type limited to the uterus and ovary. It has not spread to lymph nodes or distant sites.

Stage I endometrioid cancers

Standard treatment includes surgery to remove and stage the cancer. Sometimes this is the only treatment needed. The patient is then closely watched for signs that the cancer has come back (recurred).

For those with higher grade tumors, radiation will likely be recommended after surgery. Vaginal brachytherapy (VB), pelvic radiation, or both can be used.

Some younger patients with early endometrial cancer may have just the uterus removed without removing the ovaries. This prevents menopause and the problems that can come with it. This also increases the chance that the cancer will come back, but it doesn’t make it more likely that you will die from the cancer. This may be something that you want to discuss with your doctor.

Those who cannot have surgery because of other medical problems or age are often treated with just radiation (external radiation and/or vaginal brachytherapy).

Fertility-sparing treatment for stage IA grade 1 endometrioid cancers

For those who still want to have children, surgery may be postponed while progestin therapy is used to treat the cancer. Progestin treatment can cause the cancer to shrink or even go away for some time, giving them a chance to get pregnant. Still, this can be risky if the patient isn't watched closely. An endometrial biopsy or a D&C should be done every 3 to 6 months. If there's still no cancer after 6 months, pregnancy can be attempted     . Regular checks for the cancer will need to continue every 6 months. After childbearing is complete, a total hysterectomy with bilateral salpingectomy with or without bilateral oophorectomy is recommended because the cancer can come back again.      

Progestin treatment often doesn't work and the cancer doesn’t get better or keeps growing. Putting off surgery can give the cancer time to spread outside the uterus. If it doesn’t go away in 6 to 12 months, surgery (hysterectomy and removal of both fallopian tubes and ovaries) to remove and stage the cancer is recommended.

A second opinion from a gynecologic oncologist and pathologist (to confirm the grade of the cancer) before starting progestin therapy is important. Seeing a fertility expert is also a good idea. It's important to understand that this isn't a standard treatment and might increase risk of cancer growth and spread.

Other types of stage I endometrial cancers

Uterine cancers such as papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma are more likely to have already spread when diagnosed. If the biopsy done before surgery shows a high-grade cancer, the surgery may be more extensive. Along with the total hysterectomy, both fallopian tubes, both ovaries, and lymph nodes are removed and the omentum is biopsied.

After surgery, chemotherapy (chemo) with or without radiation therapy is given to help keep the cancer from coming back. The chemo usually includes carboplatin and paclitaxel, but other drugs can also be used.

If the cancer can't be removed with surgery, chemotherapy (chemo) with or without radiation is used. Sometimes, the tumor then shrinks so that surgery can remove it.

Treating stage II endometrial cancers

When an endometrial cancer is stage II, it has either spread to the connective tissue of the cervix or there is substantial lymphovascular space invasion (LVSI; cancer cells spread to the blood vessels or lymph vessels) or the cancer is an aggressive histologic type with any invasion into the myometrium.      

One treatment option is to have surgery first, followed by radiation therapy. If the cancer has spread to the cervix, the surgery may include a radical hysterectomy.        

Radiation therapy, often both vaginal brachytherapy and external pelvic radiation, may be given after the patient has recovered from surgery. Another option is to give the radiation therapy first, and then do a simple hysterectomy, remove both ovaries and fallopian tubes (BSO), and possible lymph node dissection or sampling.

If there’s cancer in the lymph nodes that have been removed and checked for cancer cells, the cancer is actually stage IIIC.

Some patients  with early-stage endometrial cancer might not be healthy enough to safely have surgery. These patients  are treated with external radiation and brachytherapy.

For patients with high-grade cancers, like papillary serous carcinoma or clear cell carcinoma,  surgery may include omental biopsy or omentectomy (removal of the omentum) and peritoneal biopsies along with the total hysterectomy, removal of both fallopian tubes and ovaries, assessment of the lymph nodes, and pelvic washings.

After surgery, radiation therapy, chemo, or both may be given to help keep the cancer from coming back. The chemo usually includes the drugs cisplatin or carboplatin and paclitaxel.

Someone with a stage II uterine carcinosarcoma often has the same type of surgery that’s used for a high-grade cancer. After surgery, radiation or chemo, or both may be used.           

Also included in stage II are cancers that are confined to the uterus, but molecular classification detects an abnormality in the p53 gene. This is designated stage IICmp53abn. Most endometrial cancers with an abnormality in the p53 gene are higher grade, but this classification includes lower grade tumors that are found to have this marker that is associated with worse outcomes than low-grade tumors that do not have a p53 gene abnormality.

Treating stage III endometrial cancers

Stage III endometrial cancers have spread outside of the uterus.

If the surgeon thinks that all visible cancer can be removed, a hysterectomy is done and both ovaries and fallopian tubes are removed. Sometimes those with stage III cancers need a radical hysterectomy. A pelvic and para-aortic lymph node dissection may also be done. Pelvic washings will be done, and the omentum may be removed. Some doctors will try to remove any remaining cancer (called debulking), but it isn’t clear that this helps patients live longer.

If tests done before surgery show that the cancer has spread too far to be removed completely, in rare cases, radiation therapy may be given before any surgery. It might shrink the tumor enough to make surgery an option.    

Stage IIIA endometrial cancer

 The cancer has spread to the ovary or fallopian tube and may have  spread to the outer surface of the uterus (called the serosa).  For these cancers, treatment after surgery may include chemo, radiation, or both. Radiation is given to the pelvis or to both the abdomen (belly) and pelvis. Vaginal brachytherapy is often used, too.

Stage IIIB endometrial cancer

 The cancer has spread to the vagina or to the tissues around the uterus (called the parametrium). It may have also spread to the tissues within the pelvis (called the pelvic peritoneum). After surgery, stage IIIB may be treated with chemo and/or radiation.

Stage IIIC endometrial cancer

This includes cancers that have spread to the lymph nodes in the pelvis (stage IIIC1) and those that have spread to the lymph nodes around the aorta (stage IIIC2). Treatment includes surgery, followed by chemo and/or radiation.

For those with high-grade cancers (such as papillary serous carcinoma, clear cell carcinoma, or carcinosarcoma), the surgery may include omentectomy and peritoneal biopsies along with a total hysterectomy, removal of both ovaries and fallopian tubes, pelvic and para-aortic lymph node dissections, and pelvic washings. After surgery, chemo or radiation therapy, or both may be given to help keep the cancer from coming back. The chemo usually includes cisplatin or carboplatin and paclitaxel.    

Treating stage IV endometrial cancers

Stage IVA endometrial cancers have grown into the bladder or bowel.

Stage IVB endometrial cancers have spread to the abdominal peritoneum.

Stage IVC The cancer has spread to distant sites such as lungs, liver, brain or bone or has spread to lymph nodes outside of the abdomen or lymph nodes above the kidneys.

Some endometrial cancers are stage IV because they have spread to lymph nodes in the abdomen (and not just the pelvis and para-aortic area), but they haven't spread to any other areas. Patients with this kind of cancer spread may have better outcomes if all the cancer that’s seen can be removed (debulked) and biopsies of other areas in the abdomen do not show cancer cells.

In many cases of stage IV endometrial cancer, the cancer has spread too far for it all to be removed with surgery. A hysterectomy and removal of both fallopian tubes and ovaries may still be done to prevent excessive bleeding. Radiation therapy may also be used for this reason. When the cancer has spread to other parts of the body, hormone therapy may be used. But high-grade cancers and those without detectable progesterone and estrogen receptors on the cancer cells are not likely to respond to hormone therapy.

Combinations of chemo drugs may help some patients for a time. Targeted drugs and/or immunotherapy drugs may also be options for some with advanced endometrial cancer.

Those with stage IV endometrial cancer should consider taking part in clinical trials of chemotherapy or other new treatments.

Treating recurrent endometrial cancer

A cancer that comes back  after treatment is called a recurrence. Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Treatment depends on the amount of cancer and where it is, as well as the treatment that was used the first time.

For local recurrences, such as in the pelvis, surgery (sometimes followed by radiation therapy) is used. For those with other medical conditions that make them unable to have surgery, radiation therapy alone or combined with hormone therapy tends to be used.

For a distant (in other parts of the body) recurrence, surgery and/or focused radiation therapy may be used when the cancer is only in a few small spots (like in the lungs or bones). Those with more extensive recurrences (widespread cancer) are treated like those with stage IV endometrial cancer. Low-grade cancers containing hormone receptors are more likely to respond well to hormone therapy. Higher-grade cancers are unlikely to shrink with hormone therapy but may respond to chemo, targeted therapy and immunotherapy.          

Clinical trials should be considered and may be a good option.