What is Uterine Sarcoma?

In 2014, Dionne Shepperson, then 40 and pregnant, began feeling weak and faint. Because she had in the past experienced uterine fibroids, for which she underwent surgery, she grew concerned. Shepperson also had a history of anemia, and she learned from her doctor that her blood count was critically low, putting her ability to carry and deliver her baby at risk.

She had a series of blood transfusions, her daughter was born healthy, and Shepperson’s menstrual cycle returned to normal. Then, in 2016, her periods became extremely heavy and she began passing large clots.

“I was at work and I felt a gush of blood,” recalls the 46-year-old Henrico, Virginia, resident, noting that her periods quickly became uncontainable.

She had no health insurance at the time, but fortunately, a job change in 2017 required a physical. Shepperson got the news in a follow-up phone call: Her blood count was once again critically low, and she would need transfusions to boost her hemoglobin.

In early 2018, she again began to feel weak, struggling to manage the stairs leading to her third-floor apartment. By March, her abdomen was swollen. She saw her gynecologist, who told her that her fibroids would require a hysterectomy. Without health insurance or sick time, Shepperson canceled the surgery.

About five weeks later, on her daughter’s fourth birthday, Shepperson woke up with unbearable pain in her abdomen. Her primary care doctor sent her for imaging, but an X-ray showed nothing. After a trip to the emergency room, which included an ultrasound and CT scan, she was told to see a gynecologist right away: A mass was detected on her right ovary, and a blood test revealed an elevated level of cancer antigen 125, in her blood. Her gynecologist recommended an oncology consult.

“Within a week, I was on an operating table,” Shepperson says. Still suspecting fibroids, the surgeon removed everything except her left ovary to avoid sending Shepperson into menopause. But when the pathology report came back, the news wasn’t good: Shepperson had stage 1 uterine leiomyosarcoma.

A month later, she was back in surgery to remove her left ovary and reduce the risk of recurrence. The surgeon also took out a small portion of her intestine that had initially adhered to the mass on her right ovary. Concerned that the cancer’s contact with her intestine could change the staging of the disease, the surgeon had the tissue tested, but the diagnosis remained stage 1.

DIFFICULT TO DIAGNOSE

Although her cancer is rare, occurring in about 1,200 women each year in the United States, Shepperson’s story is not. “Uterine leiomyosarcoma is difficult to differentiate from fibroids,” says Dr. Leslie Boyd, director of the Gynecologic Oncology Fellowship Program at NYU Langone Health’s Perlmutter Cancer Center in New York City. “Up to 85% of women will have fibroids, and it can be challenging to tell the difference between fibroids and uterine sarcoma.”

Sometimes interchanged with endometrial cancer, which is more common and starts in the lining of the uterus, uterine sarcoma grows in the muscles or supporting tissue. Three types exist: uterine leiomyosarcoma, endometrial stromal sarcoma and undifferentiated sarcoma. Uterine leiomyosarcoma is the most common and develops in the myometrium, a layer of the uterine wall consisting of smooth muscle tissue. Endometrial stromal sarcoma, which is rarer, develops in the connective tissues that support the lining of the uterus. Undifferentiated sarcoma, also rare but marked by its aggressiveness, can start in the uterine lining or the myometrium.

African American women are at double the risk of developing uterine sarcoma compared with Caucasian or Asian women. Other risk factors include a history of pelvic radiation or use of tamoxifen, a medication commonly used to treat certain breast cancers; never being pregnant; and certain genetic links, such as an abnormal gene that causes retinoblastoma, a form of eye cancer.

Doctors don’t typically rely on biopsies, which are used in other types of cancer, to diagnose uterine sarcoma. They might instead turn to MRI or a blood test to measure serum lactate dehydrogenase, which is elevated in some patients. However, Boyd says, both tests are imperfect.

There’s no way of confirming uterine sarcoma without surgery, according to Dr. Kristen Ganjoo, an associate professor of medicine at Stanford Medicine in California. “You may biopsy an area that doesn’t look like uterine sarcoma and the diagnosis is missed,” she says, adding that uterine sarcoma and fibroids are typically indistinguishable on scans.

Certain symptoms, such as fibroids more than 5 to 10 centimeters and those growing faster than typically expected, can raise suspicion, according to Ganjoo: “If you see a five-centimeter fibroid on ultrasound and two months later, that fibroid is 10 centimeters, that’s worrisome.”

Most fibroids should be managed conservatively, with nonsurgical treatments like nonsteroidal anti-inflammatory drugs and hormonal treatments, says Dr. Barbara Goff, a gynecologic oncologist at Seattle Cancer Care Alliance and chair of obstetrics and gynecology at the University of Washington School of Medicine. “It’s challenging to diagnose from radiographic features,” she says. Often, she becomes concerned if a patient’s fibroids are degenerating or becoming necrotic, meaning they have outgrown their blood supply, as well as if symptoms are severe and don’t respond to treatment.

Significant controversy surrounds a fibroid treatment called morcellation. In this surgical technique, a device called a laparoscopic power morcellator cuts tissue into smaller pieces that can be removed through more mini- mally invasive laparoscopic surgery. Although the proce- dure has been used for hysterectomy and myomectomy, which is the removal of noncancerous fibroids, the Food and Drug Administration issued a warning in 2018 that in women with undiagnosed uterine sarcomas, morcellation could cause cancerous tissue to spread outside the uterus. Because of this risk, some experts advise women who have fibroids to avoid using morcellation, whereas others still consider it an option for treatment.

STAGE-DRIVEN TREATMENT

Staging uterine sarcoma is a critical piece of the treatment and prognosis puzzle. Several tests may be used, including blood tests, X-ray, a transvaginal ultrasound, CT scan, MRI and cystoscopy. Patients with stage 1 uterine sarcoma, in which the disease is contained to the uterus, have about a 50% risk of recurrence, Boyd says. Broken down further, stage 1a uterine sarcoma is found less than halfway through the myometrium; in stage 1b, the cancer has spread at least halfway into the myometrium.

“With stage 1 uterine sarcoma, hysterectomy is the treatment of choice,” says Goff, adding that surgery is followed by close monitoring. “It isn’t clear that adjuvant treatment, radiation, chemotherapy or hormonal therapy, makes a difference in risk of recurrence,” she says.

In a stage 2 diagnosis, cancer has spread into the connective tissue of the cervix but remains within the uterus. These patients may have adjuvant chemotherapy, given after surgery, on a case-by-case basis, Ganjoo says. In advanced disease, stage 3 or 4, patients receive chemotherapy following surgery to prolong remissions, she adds.

Chemotherapies include Gemzar (gemcitabine) and Taxotere (docetaxel), typically given together, or Adriamycin (doxorubicin) alone. “Radiation tends not to be effective for uterine sarcoma,” Boyd says.

Regena Hammock, 51, of Flossmoor, Illinois, learned she was at high risk of uterine cancer because she began menstruating very young and for years struggled with heavy bleeding and fibroids. She had a partial hysterectomy in her early 30s and then, in her 40s, had her left ovary and one fallopian tube removed after she developed ovarian cysts.

In 2017, Hammock experienced severe abdominal pain and vomiting. She went to the emergency room, where she was told she had a mass on her abdomen. A biopsy revealed endometrial stromal sarcoma.

Hammock was treated with a chemotherapy regimen known as MAID, Mesna (mesnex), Adriamycin, Ifex (ifosfamide) and DTIC-Dome (dacarbazine), that required a five-day hospital stay every 21 days for five months. In October 2018, her doctor told her she was cancer-free, but hormone replacement therapy to balance her estrogen and progesterone, plus CT scans every six months, remain a part of her life.

THE SEARCH FOR BETTER OPTIONS

For women like Shepperson, who receive a stage 1 diagnosis, living with uterine sarcoma takes a “watch and wait” approach. “It’s constant monitoring, with a CT scan every three months,” Shepperson says. “My oncologist took me by the hand and told me the fear gets easier to deal with. He was right.”

Patients of Ganjoo with stage 1 uterine sarcoma can expect follow-up monitoring every three months during the first year, with visits alternating between her office and their gynecologic oncologist. In the second year, she sees patients every four months; in the third, fourth and fifth years, every six months. Monitoring includes blood tests for hemoglobin and kidney and liver function, as well as scans. Recurrence can occur anytime but is most likely in the first and second years after diagnosis and surgery, she says.

Conventional therapies have been disappointing for uterine sarcomas, according to Goff. Still, she remains hopeful that new research will deliver innovative options. The targeted therapy Votrient (pazopanib) for uterine leiomyosarcoma shows some promise in inhibiting new blood

vessel formation, Goff says, whereas the hormone therapies Provera (medroxyprogesterone acetate) and Megace ES (megestrol acetate) are working better to treat some endometrial stromas. Arimidex (anastrozole) can be used upfront in low-volume uterine leiomyosarcomas with positive hormone receptors, Ganjoo says.

“Personalized medicine, looking at an individual’s tumor, seeing what pathways are abnormal and what the potential targets are, holds the most promise for this tough-to-treat disease,” Goff says. “That’s where we need to go with this: understanding how this sarcoma is different from that sarcoma.”

Clinical trials are great options for patients but, because uterine sarcoma is rare, it may be limited. One current clinical trial is a phase 2 National Cancer Institute study of the impact of using the PARP inhibitor Lynparza (olaparib) plus the chemotherapy drug Temodar (temozolomide) in women with uterine leiomyosarcoma that has spread to other places in the body and for whom surgery is not an option.

“Be your own advocate,” Ganjoo advises, emphasizing the importance of seeking a second opinion. In addition, patients should make sure that they are being treated by experts who have firsthand knowledge of treating uterine sarcoma, Goff says, and at cancer centers that may offer opportunities to participate in clinical trials.

“The rarer your cancer is, the more important it is to be treated by an expert who is up to date on the literature, participating in meetings and hearing about abstracts,” Goff says. “A general oncologist might see only one or two uterine sarcomas in their entire lives.”

Hammock encourages women to consider hysterectomy if they have a history of heavy bleeding and fibroids and not put off seeing a doctor. “You have to take care of yourself,” she says.