Uterine LMS Research Updates

About Aromatase Inhibitors:

Q:  Studies on Letrozole – debate on whether it is best for Stage 1,2 Ulms instead of advanced states 3, 4:

A: “ Letrozole has been best studied (though small studies) in the metastatic setting. Here is a link to a publication from the DFCI group: https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.28476 
It’s really not clear how much benefit these drugs have, but anecdotally patients can benefit.”

  •  Matt Hemming, MD, Dana Farber Cancer Institute / LMS International Research Roundtable   Workgroup Leader for LMS cell lines / PDX model

The primary literature is in metastatic disease ( stage 4) – the only trial which attempted to answer the question in early stage disease was closed due to poor accrual.
Some of the literature in the advanced setting is below.

  • Suzanne George, Dana Farber Cancer Institute / LMS International Research Roundtable Member

Treatment of advanced uterine leiomyosarcoma with aromatase inhibitors.
O’Cearbhaill R, Zhou Q, Iasonos A, Soslow RA, Leitao MM, Aghajanian C, Hensley ML.Gynecol Oncol. 2010 Mar;116(3):424-9. doi: 10.1016/j.ygyno.2009.10.064. Epub 2009 Nov 24.PMID: 19932916
Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors.
George S, Feng Y, Manola J, Nucci MR, Butrynski JE, Morgan JA, Ramaiya N, Quek R, Penson RT, Wagner AJ, Harmon D, Demetri GD, Krasner C.Cancer. 2014 Mar 1;120(5):738-43. doi: 10.1002/cncr.28476. Epub 2013 Nov 12.Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors.
Thanopoulou E, Thway K, Khabra K, Judson I.Clin Sarcoma Res. 2014 Jun 26;4:5. doi: 10.1186/2045-3329-4-5. eCollection 2014.PMID: 25018868

Uterine LMS Research

Recent Research Warns About Use Of Power Morcellation

MedPage Today (12/9, Kuznar) reported on new data about the practice of power morcellation that “facilitates fragmentation and removal of uterine or fibroid tissue via small incisions.” A new FDA assessment in 2017 “revealed that the rates of occult uterine sarcoma and uterine leiomyosarcoma in women undergoing surgery for presumed uterine fibroids was 0.328% for uterine sarcomas, or about one in 305 women, and 0.175% for leiomyosarcomas, or about one in 570 women,” yet “recent evidence suggests a change in practice patterns since the FDA’s initial warning.” The piece highlighted a study published in the Journal of Clinical Oncology that contained “evidence on the risks of uncontained power morcellation among women undergoing laparoscopic supracervical hysterectomy/laparoscopic myomectomy (LSH/LM).”
 
 What Is Uterine Leiomyosarcoma?

A uterine leiomyosarcoma is a rare malignant (cancerous) tumor that arises from the smooth muscle lining the walls of the uterus (myometrium). There are essentially two types of muscles in the body: voluntary and involuntary. Smooth muscles are involuntary muscles; the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, the myometrium stretches during pregnancy to help accommodate the fetus and contracts during labor to help push out a baby during childbirth.

Uterine leiomyosarcoma is an extremely rare form of cancer, estimated to occur in 6 out of every 1,000,000 women in the United States each year. The average age at diagnosis is 51. Uterine leiomyosarcomas account for 1-2 percent of all malignant tumors of the uterus.

Symptoms of uterine leiomyosarcoma may vary from case to case depending upon the exact location, size, and progression of the tumor. Many women will not have any apparent symptoms (asymptomatic). The most common symptom is abnormal bleeding from the vagina and the uterus. Postmenopausal bleeding is an important factor that may indicate a uterine leiomyosarcoma.

Additional symptoms may occur including pressure or pain affecting the pelvis or stomach, abnormal vaginal discharge, and a change in bladder or bowel habits. General symptoms often associated with cancer include fatigue, fever, weight loss, and a general feeling of ill health (malaise).

Uterine leiomyosarcomas are malignant and may spread (metastasize) locally and to other areas of the body, especially the lungs and liver often causing life-threatening complications. Leiomyosarcomas recur in more than half of the cases sometimes within eight to 16 months of the initial diagnosis and treatment.

(Information from the National Organization of Rare Disorders/Diseases)

Illustration showing the fallopian tubes, body of uterus, vagina and cervix

illustration showing the female reproductive organs including location of endometrium, myometrium, serosa, fallopian tubes, ovaries, cervix and vagina
 
Uterine LMS Treatment  –  from the American Cancer Society

Leiomyosarcoma and undifferentiated sarcoma

Stages I and II

Most women have surgery to remove the uterus (hysterectomy), as well as the fallopian tubes and ovaries (bilateral salpingo-oophorectomy). Pelvic and para-aortic lymph node dissection or laparoscopic lymph node sampling may be done if swollen nodes are seen on imaging tests. During surgery, organs near the uterus and the thin membrane that lines the pelvic and abdominal cavities (called the peritoneum) are closely checked to see if the cancer has spread beyond the uterus.
Very rarely, young women with low-grade leiomyosarcomas (LMS) that have not spread beyond the uterus may be able to have just the tumor removed, leaving the uterus, fallopian tubes, and ovaries in place. This is not standard treatment, little is known about long-term outcomes, and it’s not often offered. Still, it may be a choice for some women who want to be able to have children after cancer treatment. This option has risks, so women thinking about this surgery need to talk about the pros and cons with their treatment team before making a decision. It may also be possible to leave a young woman’s ovaries in place (but remove the uterus and fallopian tubes), since it isn’t clear that this will lead to worse outcomes. Again, this is not a standard treatment, and you should discuss the risks and benefits with your doctor. In either case, close follow-up is important, and more surgery may be needed if the cancer comes back.
 
Women with stage I cancers may not need more treatment and are watched closely after surgery. In other cases, treatment with radiation, with or without chemo, may be needed after surgery if there’s a high chance of the cancer coming back in the pelvis. This is called adjuvant treatment. The goal of surgery is to take out all of the cancer, but the surgeon can only remove what can be seen. Tiny clumps of cancer cells that are too small to be seen can be left behind. Treatments given after surgery are meant to kill those cancer cells so that they don’t get the chance to grow into larger tumors. For LMS of the uterus, adjuvant radiation may lower the chance of the cancer growing back in the pelvis (called local recurrence), but it doesn’t seem to help women live longer.
 
Since the cancer can still come back in the lungs or other distant organs, some experts recommend giving chemo after surgery (adjuvant chemotherapy) for stage II cancers. Chemo is sometimes recommended for stage I LMS as well, but it’s less clear that it’s really helpful. So far, results from studies of adjuvant chemo have been promising in early stage LMS, but long-term follow-up is still needed to see if this treatment really helps women live longer. Studies of adjuvant therapy are in progress.

Stage III

Surgery is done to remove all of the cancer. This includes removing the uterus (a hysterectomy), removing both fallopian tubes and ovaries (bilateral salpingo-oophorectomy), and lymph node dissection or sampling. If the tumor has spread to the vagina, part (or even all) of the vagina will need to be removed as well.
After surgery, treatment with radiation (with or without chemo) may be offered to lower the chance that the cancer will come back.
 
Women who are too sick (from other medical problems) to have surgery may be treated with radiation and/or chemo.

Stage IV

This is divided into stage IVA and stage IVb.
Stage IVA cancers have spread to nearby organs and tissues, such as the bladder or rectum, and maybe to nearby lymph nodes. These cancers might be able to be completely removed with surgery, and this is usually done if possible. If the cancer cannot be removed completely, radiation may be given, either alone or with chemo.
Stage IVB cancers have spread outside the pelvis, most often to the lungs, liver, or bone. There’s no standard treatment for these cancers. Chemo may be able to shrink the tumors for a time, but is not thought to be able to cure the cancer. Radiation therapy, given along with chemo, may also be an option.
 
These cancers might also be treated with targeted therapy when other treatments don’t work. They’re often given along with chemo.