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NCI/PDQ^® Health professionals: Uterine Sarcoma Treatment (PDQ®)

National Cancer Institute
Ultima Vez Modificado: 18 de octubre del 2012

TABLE OF CONTENTS

• General Information About Uterine Sarcoma
  • Risk Factors
  • Prognosis
  • Related Summaries

• Cellular Classification of Uterine Sarcoma

• Stage Information for Uterine Sarcoma
  • Definitions: FIGO

• Treatment Option Overview

• Stage I Uterine Sarcoma
  • Current Clinical Trials

• Stage II Uterine Sarcoma
  • Current Clinical Trials

• Stage III Uterine Sarcoma
  • Current Clinical Trials

• Stage IV Uterine Sarcoma
  • Current Clinical Trials

• Recurrent Uterine Sarcoma
  • Current Clinical Trials

• Changes to This Summary (10/18/2012)

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
  • Disclaimer
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General Information About Uterine Sarcoma

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Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2% to 5% of all uterine malignancies. 1 The following tumors arise primarily from three distinct tissues:

1. Carcinosarcomas arising in the endometrium, in other organs of mullerian origin, and accounting for 40% to 50% of all uterine sarcomas.
2. Leiomyosarcomas arising from myometrial muscle, with a peak incidence occurring at age 50, and accounting for 30% of all uterine sarcomas.
3. Sarcomas arising in the endometrial stroma, with a peak incidence occurring before menopause for the low-grade tumors and after menopause for the high-grade tumors, and accounting for 15% of all uterine sarcomas.

The three distinct entities are often grouped under uterine sarcomas; however, each type of tumor is currently being studied in separate clinical trials.

Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal sarcomas or mullerian tumors. Controversy exists about the following issues:

• Whether they are true sarcomas.
• Whether the sarcomatous elements are actually derived from a common epithelial-cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.

The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements, such as malignant mesenchymal tissue considered possibly native to the uterus, or heterologous elements, such as striated muscle, cartilage, or bone, which are foreign to the uterus. Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.

Other rare forms of uterine sarcomas also fall under the WHO classification of mesenchymal and mixed tumors of the uterus. These include: 2 3

• Mixed endometrial stromal and smooth muscle tumors.
• Adenosarcomas, in which the epithelial elements appear benign within a malignant mesenchymal background.
• Embryonal botryoides or rhabdomyosarcomas, which are found almost exclusively in infants.
• PEComaa perivascular epithelial-cell tumor that may behave in a malignant fashion, which is the latest to be added.

(Refer to the PDQ® summary on Childhood Rhabdomyosarcoma for more information.)

Risk Factors

The only documented etiologic factor in 10% to 25% of these malignancies is prior pelvic radiation therapy, which is often administered for benign uterine bleeding that began 5 to 25 years earlier. An increased incidence of uterine sarcoma has been associated with tamoxifen in the treatment of breast cancer. Subsequently, increases have also been noted when tamoxifen was given to prevent breast cancer in women at increased riska possible result of the estrogenic effect of tamoxifen on the uterus. Because of this increase, patients on tamoxifen should have follow-up pelvic examinations and should undergo endometrial biopsy if there is any abnormal uterine bleeding. 4 5 6

Prognosis

The prognosis for women with uterine sarcoma is primarily dependent on the extent of disease at the time of diagnosis. 7 For women with carcinosarcomas, significant predictors of metastatic disease at initial surgery include: 7

• Isthmic or cervical location.
• Lymphatic vascular space invasion.
• Serous and clear cell histology.
• Grade 2 or 3 carcinoma.

The above factors in addition to the following ones correlate with a progression-free interval: 7

• Adnexal spread.
• Lymph node metastases.
• Tumor size.
• Peritoneal cytologic findings.
• Depth of myometrial invasion.

Factors that bear no relationship to the presence or absence of metastases at surgical exploration are:

• The presence or absence of stromal heterologous elements.
• The types of such elements.
• The grade of the stromal components.
• The mitotic activity of the stromal components.

In one study, women with a well-differentiated sarcomatous component or carcinosarcomas had significantly longer progression-free intervals than those with moderately to poorly differentiated sarcomas for the homologous and heterologous types. The recurrence rate was 44% for homologous tumors and 63% for heterologous tumors. The type of heterologous sarcoma had no effect on the progression-free interval.

For women with leiomyosarcomas, some investigators consider tumor size to be the most important prognostic factor; women with tumors greater than 5.0 cm in maximum diameter have a poor prognosis. 8 However, in a Gynecologic Oncology Group study, the mitotic index was the only factor significantly related to progression-free interval. 7 Leiomyosarcomas matched for other known prognostic factors may be more aggressive than their carcinosarcoma counterparts. 9 The 5-year survival rate for women with stage I disease, which is confined to the corpus, is approximately 50% versus 0% to 20% for the remaining stages.

Surgery alone can be curative if the malignancy is contained within the uterus. The value of pelvic radiation therapy is not established. Current studies consist primarily of phase II chemotherapy trials for patients with advanced disease. Adjuvant chemotherapy following complete resection for patients with stage I or II disease was not established to be effective in a randomized trial. 10 Yet, other nonrandomized trials have reported improved survival following adjuvant chemotherapy with or without radiation therapy. 11 12 13

Related Summaries

Other PDQ® summaries containing information related to uterine sarcoma include the following:

• Adult Soft Tissue Sarcoma Treatment
• Childhood Soft Tissue Sarcoma Treatment
• Endometrial Cancer Prevention
• Endometrial Cancer Screening
• Endometrial Cancer Treatment

References:

1. Forney JP, Buschbaum HJ: Classifying, staging, and treating uterine sarcomas. Contemp Ob Gyn 18(3):47, 50, 55-56, 61-62, 64, 69, 1981. [PUBMED Abstract]
2. Gershenson D, McGuire W, Gore Martin, et al.: Gynecologic Cancer: Controversies in Management. 3rd ed. New York, NY: Churchill Livingstone, 2004. [PUBMED Abstract]
3. Tavassoéli F, Devilee P, et al.: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: International Agency for Research on Cancer, 2004. [PUBMED Abstract]
4. Bergman L, Beelen ML, Gallee MP, et al.: Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet 356 (9233): 881-7, 2000. [PUBMED Abstract]
5. Cohen I: Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 94 (2): 256-66, 2004. [PUBMED Abstract]
6. Wickerham DL, Fisher B, Wolmark N, et al.: Association of tamoxifen and uterine sarcoma. J Clin Oncol 20 (11): 2758-60, 2002. [PUBMED Abstract]
7. Major FJ, Blessing JA, Silverberg SG, et al.: Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 71 (4 Suppl): 1702-9, 1993. [PUBMED Abstract]
8. Evans HL, Chawla SP, Simpson C, et al.: Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer 62 (10): 2239-47, 1988. [PUBMED Abstract]
9. Oláh KS, Dunn JA, Gee H: Leiomyosarcomas have a poorer prognosis than mixed mesodermal tumours when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynaecol 99 (7): 590-4, 1992. [PUBMED Abstract]
10. Omura GA, Blessing JA, Major F, et al.: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 3 (9): 1240-5, 1985. [PUBMED Abstract]
11. Piver MS, Lele SB, Marchetti DL, et al.: Effect of adjuvant chemotherapy on time to recurrence and survival of stage I uterine sarcomas. J Surg Oncol 38 (4): 233-9, 1988. [PUBMED Abstract]
12. van Nagell JR Jr, Hanson MB, Donaldson ES, et al.: Adjuvant vincristine, dactinomycin, and cyclophosphamide therapy in stage I uterine sarcomas. A pilot study. Cancer 57 (8): 1451-4, 1986. [PUBMED Abstract]
13. Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989. [PUBMED Abstract]

Cellular Classification of Uterine Sarcoma

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The most common histologic types of uterine sarcomas include:
• Carcinosarcomas (mixed mesodermal sarcomas [40%50%]).
• Leiomyosarcomas (30%).
• Endometrial stromal sarcomas (15%).

The uterine neoplasm classification of the International Society of Gynecologic Pathologists and the World Health Organization uses the term carcinosarcomas for all primary uterine neoplasms containing malignant elements of both epithelial and stromal light microscopic appearances, regardless of whether malignant heterologous elements are present. 1

References:

1. Silverberg SG, Major FJ, Blessing JA, et al.: Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 9 (1): 1-19, 1990. [PUBMED Abstract]

Stage Information for Uterine Sarcoma

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Definitions: FIGO

The Féderation Internationale de Gynécologie et d'Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define carcinoma of the corpus uteri, which applies to uterine sarcoma; the FIGO system is most commonly used. 1 2

Uterine sarcomas include leiomyosarcomas, endometrial stromal sarcomas, and adenosarcomas.

Table 1. Uterine Sarcoma^a

^aAdapted from FIGO Committee on Gynecologic Oncology.^bEither G1, G2, or G3 (G = grade).^cEndocervical glandular involvement only should be considered as stage I and no longer as stage II.^dPositive cytology has to be reported separately without changing the stage.

Stage
Ib	Tumor confined to the corpus uteri.
IAb	No or less than half myometrial invasion.
IBb	Invasion equal to or more than half of the myometrium.
IIb	Tumor invades cervical stroma but does not extend beyond the uterus.c
IIIb	Local and/or regional spread of the tumor.
IIIAb	Tumor invades the serosa of the corpus uteri and/or adnexae.d
IIIBb	Vaginal and/or parametrial involvement.d
IIICb	Metastases to pelvic and/or para-aortic lymph nodes.d
IIIC1b	Positive pelvic nodes.
IIIC2b	Positive para-aortic lymph nodes with or without positive pelvic lymph nodes.
IVb	Tumor invades bladder and/or bowel mucosa, and/or distant metastases.
IVAb	Tumor invasion of bladder and/or bowel mucosa.
IVBb	Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes.
1

References:

1. Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105 (2): 103-4, 2009. [PUBMED Abstract]
2. Corpus uteri. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 403-18. [PUBMED Abstract]

Treatment Option Overview

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Surgery is often the principal means of diagnosis and is the primary treatment for all patients with uterine sarcoma. If the diagnosis is known, the extent of surgery is planned according to the stage of the tumor. Hysterectomy is usually performed when a uterine malignancy is suspected, except for rare instances when preservation of the uterus in a young patient is deemed safe for the type of cancer (e.g., a totally confined low-grade leiomyosarcoma in a woman who desires to retain childbearing potential). Medically suitable patients with the preoperative diagnosis of uterine sarcoma are considered candidates for abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy. Cytologic washings are obtained from the pelvis and abdomen. Thorough examination of the diaphragm, omentum, and upper abdomen is performed.

There is no firm evidence from a prospective study that adjuvant chemotherapy or radiation therapy is of benefit for patients with uterine sarcoma. 1 In one Gynecologic Oncology Group (GOG) study, the use of adjuvant doxorubicin did not alter the survival rate of patients with resected stage I or stage II uterine sarcomas; however, interpretation of these results is difficult because this study included some patients who received radiation and three types of uterine sarcomas that have variable responses to doxorubicin. 1[Level of evidence: 1iiA] However, because the risk of disease recurrence is high even with localized presentations, many physicians have considered the use of adjuvant chemotherapy or radiation therapy. 2 A report of a study (GOG-0150 [NCT00002546]) that addressed radiation therapy versus adjuvant chemotherapy is awaited. 3

References:

1. Omura GA, Blessing JA, Major F, et al.: A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 3 (9): 1240-5, 1985. [PUBMED Abstract]
2. Kohorn EI, Schwartz PE, Chambers JT, et al.: Adjuvant therapy in mixed mullerian tumors of the uterus. Gynecol Oncol 23 (2): 212-21, 1986. [PUBMED Abstract]
3. Wolfson AH, Brady MF, Mannel RS, et al.: A Gynecologic Oncology Group randomized trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide+mesna (CIM) in optimally debulked stage I-IV carcinosarcoma (CS) of the uterus. [Abstract] J Clin Oncol 24 (Suppl 18): A-5001, 256s, 2006. [PUBMED Abstract]

Stage I Uterine Sarcoma

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Standard treatment options:

1. Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy).
2. Surgery plus pelvic radiation therapy.
3. Surgery plus adjuvant chemotherapy.
4. Surgery plus adjuvant radiation therapy as seen in the EORTC-55874 trial, for example.

In a nonrandomized, Gynecologic Oncology Group study in patients with stage I and II carcinosarcomas, those who had pelvic radiation therapy had a significant reduction of recurrences within the radiation treatment field but no alteration in survival. 1 A large nonrandomized study demonstrated improved survival and a lower local failure rate in patients with mixed mullerian tumors following postoperative external and intracavitary radiation therapy. 2 One nonrandomized study that predominantly included patients with carcinosarcomas appeared to show benefit for adjuvant therapy with cisplatin and doxorubicin. 3

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Hornback NB, Omura G, Major FJ: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int J Radiat Oncol Biol Phys 12 (12): 2127-30, 1986. [PUBMED Abstract]
2. Larson B, Silfverswírd C, Nilsson B, et al.: Mixed mí¼llerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases. Radiother Oncol 17 (2): 123-32, 1990. [PUBMED Abstract]
3. Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989. [PUBMED Abstract]

Stage II Uterine Sarcoma

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Standard treatment options:

1. Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy).
2. Surgery plus pelvic radiation therapy.
3. Surgery plus adjuvant chemotherapy.
4. Surgery plus adjuvant radiation therapy (EORTC-55874).

In a nonrandomized, Gynecologic Oncology Group study in patients with stage I and II carcinosarcomas, those who had pelvic radiation therapy had a significant reduction of recurrences within the radiation treatment field but no alteration in survival. 1 One nonrandomized study that predominantly included patients with carcinosarcomas appeared to show benefit for adjuvant therapy with cisplatin and doxorubicin. 2

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Hornback NB, Omura G, Major FJ: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int J Radiat Oncol Biol Phys 12 (12): 2127-30, 1986. [PUBMED Abstract]
2. Peters WA 3rd, Rivkin SE, Smith MR, et al.: Cisplatin and adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecol Oncol 34 (3): 323-7, 1989. [PUBMED Abstract]

Stage III Uterine Sarcoma

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Standard treatment options:

• Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and periaortic selective lymphadenectomy, and resection of all gross tumor).

Treatment options under clinical evaluation:

1. Surgery plus pelvic radiation therapy.
2. Surgery plus adjuvant chemotherapy.

Carcinosarcomas (the preferred designation by the World Health Organization) are also referred to as mixed mesodermal or mullerian tumors. Controversy exists about the following issues:

• Whether they are true sarcomas.
• Whether the sarcomatous elements are actually derived from a common epithelial cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.

The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements (such as malignant mesenchymal tissue considered possibly native to the uterus) or heterologous elements (such as striated muscle, cartilage, or bone, which are foreign to the uterus). Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.

Patients who present with uterine sarcoma have been treated on a series of phase II studies by the Gynecologic Oncology Group, including the GOG-87B trial, for example. 1 2 These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in patients with carcinosarcomas 3 and a 17.2% partial response rate in patients with leiomyosarcomas. 2

A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months). 4[Level of evidence: 1iiA] The follow-up GOG-0161 [NCT00003128] study utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4). 5 The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.490.97). 5[Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.

A role for chemotherapy as adjuvant to surgery has not yet been established.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991. [PUBMED Abstract]
2. Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992. [PUBMED Abstract]
3. Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989. [PUBMED Abstract]
4. Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000. [PUBMED Abstract]
5. Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007. [PUBMED Abstract]

Stage IV Uterine Sarcoma

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There is currently no standard therapy for patients with stage IV disease. These patients should be entered into an ongoing clinical trial.

Carcinosarcomas (the preferred designation by the World Health Organization) are also referred to as mixed mesodermal or mullerian tumors. Controversy exists about the following issues:

• Whether they are true sarcomas.
• Whether the sarcomatous elements are actually derived from a common epithelial cell precursor that also gives rise to the usually more abundant adenocarcinomatous elements.

The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements, such as malignant mesenchymal tissue considered possibly native to the uterus, or heterologous elements, such as striated muscle, cartilage, or bone, which is foreign to the uterus. Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.

Patients who present with uterine sarcoma have been treated on a series of phase II studies by the Gynecologic Oncology Group, including the GOG-87B trial, for example. 1 These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in patients with carcinosarcomas, 2 a 33% response rate in patients with endometrial stromal cell sarcomas, 3, and a 17.2% partial response rate in patients with leiomyosarcomas. 4 Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for advanced disease. 5 6 Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas, but cisplatin is inactive as first- or second-line therapy for patients with leiomyosarcomas. 1 7

A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months). 8[Level of evidence: 1iiA] The follow-up GOG-0161 [NCT00003128] study utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4). 9 The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.490.97). 9[Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991. [PUBMED Abstract]
2. Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989. [PUBMED Abstract]
3. Sutton G, Blessing JA, Park R, et al.: Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: a study of the Gynecologic Oncology Group. Obstet Gynecol 87 (5 Pt 1): 747-50, 1996. [PUBMED Abstract]
4. Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992. [PUBMED Abstract]
5. Omura GA, Major FJ, Blessing JA, et al.: A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52 (4): 626-32, 1983. [PUBMED Abstract]
6. Muss HB, Bundy B, DiSaia PJ, et al.: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 55 (8): 1648-53, 1985. [PUBMED Abstract]
7. Thigpen JT, Blessing JA, Wilbanks GD: Cisplatin as second-line chemotherapy in the treatment of advanced or recurrent leiomyosarcoma of the uterus. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol 9 (1): 18-20, 1986. [PUBMED Abstract]
8. Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000. [PUBMED Abstract]
9. Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007. [PUBMED Abstract]

Recurrent Uterine Sarcoma

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There is currently no standard therapy for patients with recurrent disease. These patients should be entered into an ongoing clinical trial.

Patients who present with uterine sarcoma have been treated on a series of phase II studies by the Gynecologic Oncology Group, including the GOG-87B trial, for example. These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in patients with carcinosarcomas, 1 a 33% response rate in patients with endometrial stromal cell sarcomas, 2 and a 17.2% partial response rate in patients with leiomyosarcomas. 3 Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for recurrent disease. 4 5 Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas, but cisplatin is inactive as first- or second-line therapy for patients with leiomyosarcomas. 6 7 A regimen of gemcitabine plus docetaxel had a 53% response rate in patients with unresectable leiomyosarcomas and is undergoing further study. 8

A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months). 9[Level of evidence: 1iiA] The follow-up GOG-0161 [NCT00003128] study utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4). 10 The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.490.97). 10[Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.

For patients with carcinosarcomas who have localized recurrence to the pelvis confirmed by computed tomographic scanning, radiation therapy may be effective palliation. Phase I and II clinical trials are appropriate for patients who recur with distant metastasis and are unresponsive to first-line phase II trials. High-dose progesterone hormone therapy may be of some benefit to patients with low-grade stromal sarcoma. 11

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Sutton GP, Blessing JA, Rosenshein N, et al.: Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 161 (2): 309-12, 1989. [PUBMED Abstract]
2. Sutton G, Blessing JA, Park R, et al.: Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: a study of the Gynecologic Oncology Group. Obstet Gynecol 87 (5 Pt 1): 747-50, 1996. [PUBMED Abstract]
3. Sutton GP, Blessing JA, Barrett RJ, et al.: Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 166 (2): 556-9, 1992. [PUBMED Abstract]
4. Omura GA, Major FJ, Blessing JA, et al.: A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52 (4): 626-32, 1983. [PUBMED Abstract]
5. Muss HB, Bundy B, DiSaia PJ, et al.: Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 55 (8): 1648-53, 1985. [PUBMED Abstract]
6. Thigpen JT, Blessing JA, Beecham J, et al.: Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 9 (11): 1962-6, 1991. [PUBMED Abstract]
7. Thigpen JT, Blessing JA, Wilbanks GD: Cisplatin as second-line chemotherapy in the treatment of advanced or recurrent leiomyosarcoma of the uterus. A phase II trial of the Gynecologic Oncology Group. Am J Clin Oncol 9 (1): 18-20, 1986. [PUBMED Abstract]
8. Hensley ML, Maki R, Venkatraman E, et al.: Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 20 (12): 2824-31, 2002. [PUBMED Abstract]
9. Sutton G, Brunetto VL, Kilgore L, et al.: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 79 (2): 147-53, 2000. [PUBMED Abstract]
10. Homesley HD, Filiaci V, Markman M, et al.: Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 25 (5): 526-31, 2007. [PUBMED Abstract]
11. Katz L, Merino MJ, Sakamoto H, et al.: Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors. Gynecol Oncol 26 (1): 87-97, 1987. [PUBMED Abstract]

Changes to This Summary (10/18/2012)

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The PDQ® cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Stage Information for Uterine Sarcoma

Updated staging information for 2010 (cited Pecorelli and Edge et al. as references 1 and 2, respectively).

This summary is written and maintained by the PDQ® Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ® Editorial Boards in maintaining the PDQ® summaries can be found on the About This PDQ® Summary and PDQ® NCI's Comprehensive Cancer Database pages.

About This PDQ® Summary

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Purpose of This Summary

This PDQ® cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of uterine sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ® Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Uterine Sarcoma Treatment are:

• Leslie R. Boyd, MD (New York University Medical Center)
• Franco M. Muggia, MD (New York University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ® Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ® summary is:

National Cancer Institute: PDQ® Uterine Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified . Available at: http://cancer.gov/cancertopics/pdq/treatment/uterinesarcoma/HealthProfessional. Accessed .

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