Options and Follow-up Care for Women with Uterine Sarcomas

An ESUN Article

Suzie Siegel

Editor's Note: Suzie Siegel has leiomyosarcoma, a rare cancer of the smooth muscle. She spent more than eighteen years as a reporter and editor at the Arkansas Democrat in Little Rock, the New Orleans Times-Picayune and the Tampa Tribune before being diagnosed with cancer.

The National Comprehensive Cancer Network has updated its guidelines to recommend more options and follow-up care for women with uterine sarcomas.

The National Comprehensive Cancer Network (NCCN) is an alliance of twenty cancer centers that work together to, among other things, develop treatment guidelines for most cancers. NCCN is also dedicated to research that improves the quality, effectiveness, and efficiency of cancer care. The NCCN Clinical Practice Guidelines in Oncology™ are viewed by many as the standard for clinical policy. 

Joan McClure, senior vice president of clinical information and publications, summarized the changes during a telephone interview from the nonprofit NCCN headquarters in Jenkintown, Penn.

On its Web pages for uterine and other soft-tissue sarcomas, the National Cancer Institute (NCI) doesn’t recognize gemcitabine and docetaxel as effective. I discussed this with Dr. Edward Trimble, head of NCI’s Gynecologic Cancer Therapeutics & Quality of Cancer Care Therapeutics, at the annual meeting of the Society of Gynecologic Oncologists (SGO) in March 2006 in Palm Springs, Calif.

Trimble said he would look into the work of Dr. Martee Hensley, a medical oncologist from Memorial Sloan-Kettering Cancer Center in New York. Hensley was one of three doctors who presented papers on the efficacy of gemcitabine plus docetaxel at the annual conference of the Connective Tissue Oncology Society (CTOS) in November 2005 in Boca Raton, Fla.

On its Web site, the NCI notes that "uterine sarcomas comprise less than 1 percent of gynecologic malignancies."  For Hensley, however, "about one-third of my clinical practice is women with uterine sarcomas; and uterine sarcoma research comprises nearly all of my research efforts. In response to a clear clinical need for further treatment options for women with advanced leiomyosarcoma, I wrote and conducted the first clinical trial of fixed-dose-rate gemcitabine plus docetaxel. This was a phase II study. We had clear objective responses in about half of patients. This level of efficacy was seen even among patients who had previously been treated with doxorubicin-based therapy." 

"The results of this trial were published in the Journal of Clinical Oncology in 2002. It is gratifying to see this treatment regimen grow in its use. I serve as the principal investigator for two Gynecologic Oncology Group studies of gemcitabine plus docetaxel for uterine leiomyosarcoma."

Using chemotherapy as adjuvant treatment – for example, after a tumor has been removed – remains controversial, however.

"Thus far, there are no randomized, controlled trials that show that adjuvant chemotherapy for stage I or II, completely resected, uterine sarcomas leads to longer survival," Hensley said. "However, given the rarity of the disease, there are few data available. We are currently conducting a trial of adjuvant chemotherapy for women with stage I or II high-grade uterine leiomyosarcoma. This is a multi-center trial conducted through SARC." SARC stands for the "Sarcoma Alliance through Research and Collaboration."  

She addressed other changes in the NCCN guidelines. "Like [other] soft-tissue sarcoma, uterine sarcomas can metastasize to the lungs," Hensley said. "Imaging the chest is a very reasonable step."

Although the NCCN guidelines don’t call for imaging of the abdomen and pelvis, she noted that "clinical trials for uterine sarcomas frequently require periodic imaging of the chest, abdomen, and pelvis to help us determine response to treatment and/or whether there is evidence of recurrence." 

In regard to hormone therapy, she said, "low-grade endometrial stromal sarcomas may respond to hormonal manipulation, and this is a very reasonable strategy for low-grade ESS. Data are lacking regarding the efficacy of hormonal treatments for high-grade undifferentiated sarcomas and high-grade leiomyosarcoma. Clinical trials addressing this question are needed." 

One hormone treatment, the drug Tamoxifen, has been linked to uterine cancer. PDRhealth is one of many Web sites that have reported this; see. e.g., Uterine sarcomas in breast cancer patients treated with tamoxifen, by M. Arenas et al. Int J Gynecol Cancer, 2006 Mar-Apr;16(2):861-5.

Gynecologic oncologists serve on a panel that writes the NCCN guidelines for uterine cancer, including uterine sarcoma, while a panel of sarcoma doctors writes guidelines for other soft-tissue sarcomas. McClure said all guidelines receive a multidisciplinary review. The two sets of guidelines are:

Guidelines are updated at least once a year. Members of the public are not told what is said in panel discussions, McClure said. Thus, she said, she cannot reveal who pushed for changes or why they were made.

At last year’s CTOS conference, Dr. Robert Benjamin, director of the Sarcoma Center at the M.D. Anderson Cancer Center in Houston, promised that sarcoma doctors would write the NCCN guidelines for uterine sarcomas in the future. The NCCN has not announced that.

The uterine sarcoma guidelines use International Federation of Gynecologic and Obstetric (FIGO) staging while the soft-tissue guidelines rely on American Joint Committee on Cancer (AJCC) staging. That would mean leiomyosarcoma that starts in the uterus would be staged differently from retroperitoneal leiomyosarcoma, for example.

Most NCCN panels prefer AJCC staging, McClure said. This system takes more factors into consideration. Under FIGO staging, for example, a tumor that has not spread out of the uterus is stage 1. Under the AJCC system, the same tumor would be classified as stage 2 if the cells were poorly differentiated, which means a higher grade and a more aggressive tumor.

The National Cancer Institute also uses FIGO staging for uterine sarcomas and AJCC staging for all other soft-tissue sarcomas. But the NCI explains different prognostic factors for different uterine sarcomas.

Although different staging systems may confuse patients, Trimble said different systems shouldn’t hamper research because FIGO staging can be translated into AJCC staging easily. He also said gynecologic oncologists are re-examining the FIGO system.  

"I am interested in which staging system best describes prognosis," Hensley said. "We are attempting to collect information on both staging systems for patients on our adjuvant studies so that we may be able to compare the systems." 

She and Dr. Igor Matushansky of Memorial Sloan-Kettering Cancer Center recently published a study saying, "The clinical implications of this discordance are obvious since it makes comparisons of clinical trials, and attempts at combining the results of multiple trials, difficult."

Why does the NCCN put uterine sarcoma under uterine cancer, instead of soft-tissue sarcoma? "I cannot speak for the NCCN, but in practice, most uterine sarcomas are likely diagnosed by gynecologists and gynecologic oncologists," Hensley said, "and perhaps the NCCN wants to make sure that their management guidelines are seen by the appropriate ‘audience’." On its Web site, the NCCN is described as "an alliance of twenty of the world's leading cancer centers."  These cancer centers often have both gynecologic and sarcoma programs. But many patients will be seen by someone outside of one of these large cancer centers.

Because sarcomas are rare, many doctors rely on the guidelines. As its Web site indicates: "The NCCN guidelines have become the most widely used in oncology practice." SARC will be working with the NCCN to translate the professional guidelines for bone and soft-tissue sarcomas into guidelines that can be read more easily by patients, McClure said. No announcement has been made on translating the guidelines for uterine sarcomas.

Like the NCCN, the National Cancer Institute has different Web pages for uterine sarcomas and adult soft-tissue sarcomas:

To explain why different doctors write these sections, Trimble said the doctors who care for patients often do the research. Orthopedic surgeons did the initial studies on extremity sarcomas, he said, while gynecologic oncologists looked at gynecologic sarcomas. Sarcoma programs have grown to include medical oncologists and other specialties. I asked him why the NCI’s section for adult soft-tissue sarcomas linked to childhood soft-tissue sarcomas, but not uterine sarcomas. The NCI’s treatment information for patients with uterine sarcomas didn’t mention that they were soft-tissue sarcomas, nor did it offer a link to the soft-tissue section. The NCI will consider changing its Web sites to add this information, Trimble said in March. In April, prominent changes were made to link these sections. For uterine sarcomas, the NCI says doctors may order a CA 125 blood test. That is generally used to detect ovarian carcinoma. Trimble, a gynecologic oncologist, pointed out that doctors often don’t know a patient has sarcoma before surgery, and thus, will perform various diagnostic tests, such as CA 125. He wouldn’t recommend the test as a follow-up for sarcoma patients, however. The NCI site clarifies this. The NCI also said lymph nodes are normally removed when a woman has uterine sarcoma. That has been changed. (On its soft-tissue pages, it notes that sarcoma is found in lymph nodes in less than 3 percent of patients.)

Most studies of gynecologic sarcomas are done through the Gynecologic Oncology Group, one of nine cooperatives sponsored by the NCI to do clinical trials, Trimble said. The studies are multidisciplinary, involving surgical, radiation and medical oncologists.

The Connective Tissue Oncology Society has been lobbying for a similar group for sarcomas, he said, but the NCI lacks the money to expand. On the Research on Cancers in Women page of NCI’s Office of Women’s Health, the topic of disease-specific research shows nothing on sarcomas. The program is small, Trimble explained, and lacks money to expand.

The NCI’s Report of the Gynecologic Cancers Progress Review Group in 2001 makes no mention of sarcomas in its 116 pages. That’s because the group had limited time, and the NCI asked it to focus on the major cancers, Trimble said. The NCI lists national organizations that help people with cancer. No sarcoma organizations are included, but Trimble said they can ask to be added.

I called and emailed the NCI's Cancer Information Service (CIS) and said I had vaginal leiomyosarcoma. I was directed to a link for patient information for vaginal cancer, which lists two types of carcinomas. The information for professionals does mention vaginal sarcoma, however. Because so many types of cancer exist, the CIS specialists can’t be familiar with all of them, Trimble said. Nor are they doctors. "Our CIS folks have the most experience with the more common cancers."

In December, the NCI Listens and Learns program sought comments on how to publicize the CIS. Almost half the comments came from sarcoma patients and advocates, saying they hesitated to recommend the CIS until it learned more about sarcomas. In its Executive Summary, the NCI notes the complaints, but had not issued a response by the time this article was written. 

V3N3 ESUN Copyright © 2006 Liddy Shriver Sarcoma Initiative.