Uterine Sarcoma

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of uterine sarcomas.

Uterine Sarcoma

General Information

Note: Separate PDQ summaries on Endometrial Cancer Treatment, Screening for Endometrial Cancer, Prevention of Endometrial Cancer, and Adult Soft Tissue Sarcoma are also available.

Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2% to 5% of all uterine malignancies.¹ These tumors arise primarily from two distinct tissues: 1) leiomyosarcoma from myometrial muscle and 2) mesodermal (mullerian) and stromal sarcomas from endometrial epithelium. The only documented etiologic factor in 10% to 25% of these malignancies is prior pelvic radiation therapy, often administered for benign uterine bleeding 5 to 25 years earlier.

The prognosis for patients with uterine sarcoma is primarily dependent on the extent of disease at the time of diagnosis.² For carcinosarcomas (mixed mesodermal tumors), isthmic or cervical location, lymphatic vascular space invasion, serous and clear cell histology, and grade 2 or 3 carcinoma are all significant predictors of metastatic disease at initial surgery.² These factors, along with adnexal spread, lymph node metastases, tumor size, peritoneal cytologic findings, and depth of myometrial invasion correlate with progression-free interval.² The presence or absence of stromal heterologous elements, the types of such elements, the grade of the stromal components, and the mitotic activity of the stromal components bear no relationship to the presence or absence of metastases at surgical exploration. However, in one study, women with a well-differentiated sarcomatous component or carcinosarcoma had significantly longer progression-free intervals than those with moderate- to poorly differentiated sarcomas for both 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 leiomyosarcomas, some consider tumor size to be the most important prognostic factor; patients with tumors greater than 5.0 centimeters in maximum diameter have a poor prognosis.³ However, in a Gynecologic Oncology Group study, the mitotic index was the only factor significantly related to progression-free interval.² Leiomyosarcomas matched for other known prognostic factors may be more aggressive than their carcinosarcoma counterparts.⁴ The 5-year survival for patients with stage I disease 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 advanced disease. Adjuvant chemotherapy following complete resection (stage I and II) has not been established to be effective in a randomized trial.⁵ Yet, other nonrandomized trials have reported improved survival following adjuvant chemotherapy with or without radiation therapy.^6,7,8,

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.

² 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.

³ 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.

⁴ 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.

⁵ 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.

⁶ 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.

⁷ 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.

⁸ 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.

Cellular Classification

The most common histologic types of uterine sarcomas are:
• Carcinosarcoma (mixed mesodermal sarcomas [50%]).
• Leiomyosarcoma (30%).
• Endometrial stromal sarcoma (15%).

The new uterine neoplasm classification of the International Society of Gynecologic Pathologists uses the term carcinosarcoma 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,

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.

Stage Information

The FIGO staging for carcinoma of the corpus uteri has been applied to uterine sarcoma.^1,

Stage I

Stage I sarcoma is confined to the corpus uteri. This stage accounts for 50% of all presentations.

• Stage IA: tumor limited to endometrium.
• Stage IB: invasion to less than 50% of the myometrium.
• Stage IC: invasion to more than 50% of the myometrium.

Stage II

Stage II uterine sarcoma means the cancer has involved the corpus and the cervix but has not extended outside the uterus.

• Stage IIA: endocervical glandular involvement only.
• Stage IIB: cervical stromal invasion.

Stage III

Stage III uterine sarcoma means extension outside of the uterus but confined to the true pelvis.

• Stage IIIA: tumor invades serosa and/or adnexae and/or positive peritoneal cytology.
• Stage IIIB: metastases to pelvic and/or para-aortic lymph nodes.

Stage IV

Stage IV uterine sarcoma means involvement of the bladder or bowel mucosa or metastasis to distant sites.

• Stage IVA: tumor invasion of bladder and/or bowel mucosa.
• Stage IVB: distant metastases, including intra-abdominal and/or inguinal lymph nodes.

¹ Shepherd JH: Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol 96 (8): 889-92, 1989.

Treatment Option Overview

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 are 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 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,

The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.

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.

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.

Stage I Uterine Sarcoma

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.^1,

In a nonrandomized Gynecologic Oncology Group study in patients with stage I and II carcinosarcoma, those who had pelvic radiation therapy had a significant reduction of recurrences within the radiation treatment field but no alteration in survival.² 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.³ One nonrandomized study appears to show benefit for adjuvant therapy with cisplatin and doxorubicin.^4,

¹ Pecorelli SL, European Organization for Research and Treatment of Cancer: Phase III Randomized Study of Adjuvant Pelvic Radiotherapy Versus Observation Alone in Patients With Completely Resected, Stage I or II, High-Grade Uterine Sarcoma, EORTC-55874, Clinical trial, Closed.

² 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.

³ Larson B, Silfverswärd C, Nilsson B, et al.: Mixed müllerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases. Radiother Oncol 17 (2): 123-32, 1990.

⁴ 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.

Stage II Uterine Sarcoma

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.^1,

In a nonrandomized Gynecologic Oncology Group study in patients with stage I and II carcinosarcoma, those who had pelvic radiation therapy had a significant reduction of recurrences within the radiation treatment field but no alteration in survival.² One nonrandomized study appears to show benefit for adjuvant therapy with cisplatin and doxorubicin.^3,

¹ Pecorelli SL, European Organization for Research and Treatment of Cancer: Phase III Randomized Study of Adjuvant Pelvic Radiotherapy Versus Observation Alone in Patients With Completely Resected, Stage I or II, High-Grade Uterine Sarcoma, EORTC-55874, Clinical trial, Closed.

² 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.

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.

Stage III Uterine Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Standard treatment options:

1. Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and periaortic selective lymphadenectomy, and resection of all gross tumor).
2. Surgery plus pelvic radiation therapy.
3. Surgery plus adjuvant chemotherapy.

Patients who present with measurable disease have been treated on a series of Phase II studies by the Gynecologic Oncology Group (GOG).^1,2,3, In separate studies of patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in mixed mesodermal tumors⁴ and a 17.2% partial response rate in leiomyosarcomas.³ The GOG has also completed a randomized comparison of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcoma (mixed mesodermal sarcoma).⁵ The study demonstrated a higher response rate and longer progression-free survival on the combination arm. Survival, however, was not improved by the addition of cisplatin, and the authors concluded that use of the combination was not justified because of increased toxic effects.^5,[Level of evidence: 1iiA]

¹ Sutton GP, Gynecologic Oncology Group: Phase II Master Protocol Study of Chemotherapeutic Agents in the Treatment of Recurrent or Advanced Uterine Sarcomas --- IFF plus Mesna (Summary Last Modified 04/93), GOG-87B, Clinical trial, Completed.

² 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.

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.

⁴ 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.

⁵ 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.

Stage IV Uterine Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

There is currently no standard therapy for patients with stage IV disease. These patients should be entered into an ongoing clinical trial. Information about ongoing clinical trials is available at the NCI Web site.

Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for advanced disease.^1,2 Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas (mixed mesodermal tumors), but is inactive as first- or second-line therapy of leiomyosarcoma.^3,4 Patients who present with measurable disease have been treated on a series of Phase II studies by the Gynecologic Oncology Group (GOG).^3,5 In separate studies of patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in mixed mesodermal tumors ^6,, a 33% response rate in endometrial stromal cell sarcomas ^7,, and a 17.2% partial response rate in leiomyosarcomas.⁸ The GOG has also completed a randomized comparison of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcoma (mixed mesodermal tumor).⁹ The study demonstrated a higher response rate and longer progression-free survival on the combination arm. Survival, however, was not improved by the addition of cisplatin, and the authors concluded that use of the combination was not justified because of increased toxic effects.^9,[Level of evidence: 1iiA]

¹ 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.

² 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.

³ 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.

⁴ 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.

⁵ Sutton GP, Gynecologic Oncology Group: Phase II Master Protocol Study of Chemotherapeutic Agents in the Treatment of Recurrent or Advanced Uterine Sarcomas --- IFF plus Mesna (Summary Last Modified 04/93), GOG-87B, Clinical trial, Completed.

⁶ 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.

⁷ 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.

⁸ 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.

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.

Recurrent Uterine Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

There is currently no standard therapy for patients with recurrent disease. These patients should be entered into an ongoing clinical trial. Information about ongoing clinical trials is available at the NCI Web site.

Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for recurrent disease.^1,2 Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas (mixed mesodermal tumors), but is inactive as first- or second-line therapy of leiomyosarcoma.^3,4 A regimen of gemcitabine plus docetaxel had a 53% response rate in patients with unresectable leiomyosarcoma and is undergoing further study.⁵ Patients who present with measurable disease have been treated on a series of Phase II studies by the Gynecologic Oncology Group (GOG).⁶ Ifosfamide had a 32.2% response rate in carcinosarcomas ^7,, a 33% response rate in endometrial stromal cell sarcomas ^8,, and a 17.2% partial response rate in leiomyosarcomas.⁹ The GOG has also completed a randomized comparison of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas.¹⁰ The study demonstrated a higher response rate and longer progression-free survival on the combination arm. Survival, however, was not improved by the addition of cisplatin, and the authors concluded that use of the combination was not justified because of increased toxic effects.^10,[Level of evidence: 1iiA]

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,

¹ 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.

² 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.

³ 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.

⁴ 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.

⁵ 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.

⁶ Sutton GP, Gynecologic Oncology Group: Phase II Master Protocol Study of Chemotherapeutic Agents in the Treatment of Recurrent or Advanced Uterine Sarcomas --- IFF plus Mesna (Summary Last Modified 04/93), GOG-87B, Clinical trial, Completed.

⁷ 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.

⁸ 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.

⁹ 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.

¹⁰ 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.

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.

Changes to This Summary (07/13/2006)

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.

Recurrent Uterine Sarcoma

Added text about a regimen of gemcitabine plus docetaxel (cited Hensley et al. as reference 5).

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