Tuesday, July 28, 2015

NCCN revises guidelines on uterine sarcoma

By Suzie Siegel

Guidelines on the treatment of uterine sarcoma have been “extensively revised” this year, according to the National Comprehensive Cancer Network® (NCCN®).

The nonprofit NCCN, an alliance of 26 leading cancer centers in the U.S., publishes separate guidelines for uterine cancers and soft-tissue sarcomas. Two separate panels of experts write them. In the past, some recommendations for uterine leiomyosarcoma (uLMS) differed from recommendations for LMS elsewhere in the body.

Dr. Suzanne George
In 2005, I urged sarcoma specialists to address this discrepancy. The next year, I wrote about the problem here and here. I stopped checking the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) until recently when I saw that Dr. Suzanne George, a renowned medical oncologist in sarcoma at Dana-Farber Cancer Institute in Boston, had been added to the uterine cancer panel in February 2013 as a liaison. I was thrilled, as were other LMS advocates.

“The NCCN Guidelines Panels for Soft Tissue Sarcoma and Cervical/Uterine Cancers have worked together since that time,” according to a statement from Drs. George, Wui-Jin Koh and Benjamin E. Greer. The latter two co-chair the NCCN Guidelines® panel for Cervical Cancer and Uterine Neoplasms. Dr. Koh is a radiation oncologist and Dr. Greer is a gynecologic oncologist, both at the Fred Hutchinson Cancer Research Center in Seattle.

“Uterine sarcomas are uncommon cancers, and women who are diagnosed with these tumors can be cared for by multiple disciplines, including gynecologic oncology, sarcoma-focused medical oncology, surgical oncology, radiation oncology and pathology,” Dr. George said in a separate statement. “It is our responsibility to work together across disciplines to help develop the best guidance possible for the care of women with uterine sarcomas.

"NCCN provides a unique opportunity to bring disciplines together to establish multidisciplinary clinical treatment guidelines with the aim to optimize patient care. It is an extension of the NCCN Mission to create the GYN/SARCOMA liaison position, which allows for collaboration between the Sarcoma panel and the Cervical/Uterine panel in the management of uterine sarcomas.”

The NCCN Guidelines for Uterine Neoplasms (v. 2.2015) primarily focus on the three most common forms of uterine sarcoma: uterine leiomyosarcoma (uLMS), which is the most common; low-grade endometrial stromal sarcoma (ESS); and high-grade undifferentiated endometrial sarcoma. This last category is treated similarly to uLMS. The Guidelines note that these categories are changing as we learn more. For example, some low-grade uLMS is being downgraded to tumors of unknown malignant potential, which are not considered cancers.

The NCCN Guidelines now separate three pathways toward diagnosis and treatment: total or supracervical hysterectomy; biopsy or myomectomy; and "any modality." The Guidelines state that sarcomas should be removed whole, not cut up (morcellated). However, some tumors fall apart on their own or become fragmented. According to the Guidelines, if a tumor was removed in pieces, doctors can consider a second surgery to remove any tumor fragments that may have been left behind.

Ovaries can be left in select patients with early-stage uLMS, but removing lymph nodes is controversial, the Guidelines say. Pelvic radiation remains controversial and isn't recommended routinely for stage I uLMS, the Guidelines say, adding that tumor-directed radiation therapy may be appropriate for people with higher-stage disease, depending on individual circumstances.

It's still not proven that chemo helps women with stage I uLMS if their tumor has been removed completely, but the Guidelines say some doctors may want to consider it because of the risk of relapse. More doctors will consider it for stages II and III. It is generally recommended for stage IV as well as for anyone with uLMS that wasn't completely removed in surgery.

If a uLMS patient is going to do chemo, the Guidelines recommend doctors try gemcitabine (Gemzar) + docetaxel (Taxotere) first. The Guidelines note a trend to use dacarbazine as a standard treatment for comparison in clinical trials, and say trabectedin (Yondelis) can be useful. However, according to the Guidelines, in the U.S. “trabectedin is currently not available outside of a clinical trial. Enrollment in clinical trials is strongly recommended."

For follow-up, the Guidelines propose a physical exam every 3 months for 2 years and then every 6-12 months. Also, doctors should consider CT imaging of the chest/abdomen/pelvis every 3-6 months for 2-3 years, with other imaging (MRI/PET) as clinically indicated. But they also caution: "Patients with bleeding (vaginal, bladder, or rectal), decreased appetite, weight loss, pain (in the pelvis, abdomen, hip, or back), cough, shortness of breath, and swelling (in the abdomen or legs) should seek prompt evaluation and not delay until the next scheduled appointment."

The Guidelines note that uLMS will return in 50 percent to 70 percent of patients. They urge doctors to educate patients on "symptoms of potential recurrence, lifestyle, obesity, exercise, and nutrition counseling" as well as "sexual health, vaginal dilator use, and vaginal lubricants/moisturizers." They recommend their Guidelines on Survivorship as well as the American Cancer Society's pages on survivorship as an additional resource.

People who are otherwise in good health are likely to get through surgery and other treatment more easily. But Drs. George, Koh and Greer clarified that: “There is no evidence that lifestyle choices impact risk of leiomyosarcoma.”

The Guidelines recommend hormone therapy for "ESS only," but add: "Aromatase inhibitors can be considered for ER/PR-expressing uLMS." They cite a study by Dr. George that says doctors are trying to determine whether suppressing estrogen helps patients with uLMS whose tumors express estrogen and/or progesterone receptors.

Observation without treatment is now an option for stage I ESS after surgery.

You can sign up for free to read this year’s NCCN Guidelines: http://www.nccn.org/professionals/default.aspx 

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms V.2.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed Feb. 2, 2015. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

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