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Uterine sarcoma


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
Stage I
Stage II
Stage III
Stage IV
TREATMENT OPTION OVERVIEW
STAGE I UTERINE SARCOMA
STAGE II UTERINE SARCOMA
STAGE III UTERINE SARCOMA
STAGE IV UTERINE SARCOMA
RECURRENT UTERINE SARCOMA

GENERAL INFORMATION

Uterine sarcomas comprise less than 1% of gynecologic malignancies and 2%-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%-25% of these malignancies is prior pelvic radiation, often administered for benign uterine bleeding 5 to 25 years earlier.

The prognosis for uterine sarcoma is primarily dependent on the extent of disease at the time of diagnosis.[2] For carcinosarcomas (malignant 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; 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 mixed mesodermal counterparts.[4] The five-year survival for patients with stage I disease confined to the corpus is approximately 50% versus 0%-20% for the remaining stages.

Surgery alone can be curative if the malignancy is contained within the uterus. The value of pelvic radiation 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.[6-8]

References:

  1. Forney JP, Buschbaum HJ: Classifying, staging, and treating uterine sarcomas. Contemporary 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): 1702-1709, 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): 2239-2247, 1988.

  4. Olah 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. British Journal of Obstetrics and Gynaecology 99(7): 590-594, 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. Journal of Clinical Oncology 3(9): 1240-1245, 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. Journal of Surgical Oncology 38(4): 233-239, 1988.

  7. Van Nagell JR, Hanson MB, Donaldson ES, et al.: Adjuvant vincristine, dactinomycin, and cyclophosphamide therapy in stage I uterine sarcomas. A pilot study. Cancer 57(8): 1451-1454, 1986.

  8. Peters WA, Rivkin SE, Smith MR, et al.: Cisplatin and Adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecologic Oncology 34(3): 323-327, 1989.


CELLULAR CLASSIFICATION

The most common histologic types of uterine sarcomas are carcinosarcoma (mixed mesodermal sarcomas - 50%), leiomyosarcoma (30%), and 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 or not 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. International Journal of Gynecological Pathology 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 half of the myometrium
stage IC: invasion to greater than half 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

References:

  1. Shepherd JH: Revised FIGO staging for gynaecological cancer. British Journal of Obstetrics and Gynaecology 96(8): 889-892, 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.

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. Journal of Clinical Oncology 3(9): 1240-1245, 1985.

  2. Kohorn EI, Schwartz PE, Chambers JT, et al.: Adjuvant therapy in mixed mullerian tumors of the uterus. Gynecologic Oncology 23(2): 212-221, 1986.


STAGE I UTERINE SARCOMA

Treatment options:

1. Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy).

2. Surgery plus pelvic irradiation.

3. Surgery plus adjuvant chemotherapy.

4. Surgery plus adjuvant irradiation.[1]

In a nonrandomized Gynecologic Oncology Group study in stage I and II mixed mesodermal sarcoma patients, those who had pelvic radiation 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]

References:

  1. Pecorelli SL, EORTC Gynecological Cancer Cooperative Group: Phase III Comparison of Adjuvant Radiotherapy vs Observation Only in Patients with Totally Resected Stage I/II High-Grade Uterine Sarcoma (Summary Last Modified 12/1995), EORTC-55874, clinical trial, active, 04/01/1988.

  2. Hornback NB, Omura G, Major FJ.: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. International Journal of Radiation Oncology, Biology, Physics 12(12): 2127-2130, 1986.

  3. Larson B, Silfversward C, Nilsson B, et al.: Mixed Mullerian tumours of the uterus - prognostic factors: a clinical and histopathologic study of 147 cases. Radiotherapy and Oncology 17(2): 123-132, 1990.

  4. Peters WA, Rivkin SE, Smith MR, et al.: Cisplatin and Adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecologic Oncology 34(3): 323-327, 1989.


STAGE II UTERINE SARCOMA

Treatment options:

1. Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and periaortic selective lymphadenectomy).

2. Surgery plus pelvic irradiation.

3. Surgery plus adjuvant chemotherapy.

4. Surgery plus adjuvant irradiation.[1]

In a nonrandomized Gynecologic Oncology Group study in stage I and II mixed mesodermal sarcoma patients, those who had pelvic radiation 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]

References:

  1. Pecorelli SL, EORTC Gynecological Cancer Cooperative Group: Phase III Comparison of Adjuvant Radiotherapy vs Observation Only in Patients with Totally Resected Stage I/II High-Grade Uterine Sarcoma (Summary Last Modified 12/1995), EORTC-55874, clinical trial, active, 04/01/1988.

  2. Hornback NB, Omura G, Major FJ.: Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. International Journal of Radiation Oncology, Biology, Physics 12(12): 2127-2130, 1986.

  3. Peters WA, Rivkin SE, Smith MR, et al.: Cisplatin and Adriamycin combination chemotherapy for uterine stromal sarcomas and mixed mesodermal tumors. Gynecologic Oncology 34(3): 323-327, 1989.


STAGE III UTERINE SARCOMA

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 irradiation.

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).[1-3] In separate studies of patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in mixed mesodermal tumors[4] and a 17.2% partial response rate in leiomyosarcomas.[3] The GOG has activated a randomized comparison of ifosfamide with or without cisplatin for first-line therapy of mixed mesodermal patients with measurable advanced or recurrent disease.[5]

References:

  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, 12/28/1994.

  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 Gynecology Oncology Group Study. Journal of Clinical Oncology 9(11), 1962-1966, 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. American Journal of Obstetrics and Gynecology 166(2): 556-559, 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). American Journal of Obstetrics and Gynecology 161(2): 309-312, 1989.

  5. Sutton GP, Gynecologic Oncology Group: Phase III Study of IFF and the Uroprotector Mesna Administered Alone or with CDDP in Patients with Advanced or Recurrent Mixed Mesodermal Tumors of the Uterus (Summary Last Modified 08/95), GOG-108, clinical trial, closed, 07/29/1996.


STAGE IV UTERINE SARCOMA

There is currently no standard therapy for patients with stage IV disease. These patients should be entered into an ongoing clinical trial. 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 mixed mesodermal sarcomas, 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 activated a randomized comparison of ifosfamide with or without cisplatin for first-line therapy of mixed mesodermal patients with measurable advanced or recurrent disease.[9]

References:

  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): 626-632, 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): 1648-1653, 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 Gynecology Oncology Group Study. Journal of Clinical Oncology 9(11), 1962-1966, 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. American Journal of Clinical Oncology 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, 12/28/1994.

  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). American Journal of Obstetrics and Gynecology 161(2): 309-312, 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. Obstetrics and Gynecology 87(5, Pt 1): 747-750, 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. American Journal of Obstetrics and Gynecology 166(2): 556-559, 1992.

  9. Sutton GP, Gynecologic Oncology Group: Phase III Study of IFF and the Uroprotector Mesna Administered Alone or with CDDP in Patients with Advanced or Recurrent Mixed Mesodermal Tumors of the Uterus (Summary Last Modified 08/95), GOG-108, clinical trial, closed, 07/29/1996.


RECURRENT UTERINE SARCOMA

There is currently no standard therapy for patients with recurrent disease. These patients should be entered into an ongoing clinical trial. 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 mixed mesodermal sarcomas, 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).[5] 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 activated a randomized comparison of ifosfamide with or without cisplatin for first-line therapy of mixed mesodermal patients with measurable advanced or recurrent disease.[9]

For patients with mixed mesodermal sarcoma who have localized recurrence to the pelvis confirmed by computed tomographic scanning, radiation 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.[10]

References:

  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): 626-632, 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): 1648-1653, 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 Gynecology Oncology Group Study. Journal of Clinical Oncology 9(11), 1962-1966, 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. American Journal of Clinical Oncology 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, 12/28/1994.

  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). American Journal of Obstetrics and Gynecology 161(2): 309-312, 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. Obstetrics and Gynecology 87(5, Pt 1): 747-750, 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. American Journal of Obstetrics and Gynecology 166(2): 556-559, 1992.

  9. Sutton GP, Gynecologic Oncology Group: Phase III Study of IFF and the Uroprotector Mesna Administered Alone or with CDDP in Patients with Advanced or Recurrent Mixed Mesodermal Tumors of the Uterus (Summary Last Modified 08/95), GOG-108, clinical trial, closed, 07/29/1996.

  10. 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. Gynecologic Oncology 26(1): 87-97, 1987.

Date Last Modified: 03/1999



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