Uterine Sarcomas | Chris O'Brien Lifehouse

Uterine sarcomas are uncommon tumours, comprising about 5% of all malignant uterine tumours and less than 1% of all female cancers. There are a number of classification systems, but in essence the most common varieties are the mixed Mullerian tumour (MMT), comprising approximately 50% of all uterine sarcomas, leiomyosarcoma (LMS) comprising 40% of sarcomas and endometrial stromal sarcoma (ESS) comprising approximately 8% of uterine sarcomas.

Abnormal vaginal bleeding (menorrhagia or postmenopausal bleeding) is the most common symptom. Endometrial biopsy will be diagnostic in 76% of MMT. The preoperative diagnosis of LMS is however unreliable.

Uterine sarcomas are staged according to the FIGO system for uterine carcinomas. Patients thought to have early stage disease on clinical grounds will be found to have extrauterine spread i.e. be up-staged in up to 50% cases if surgically staged.

Leiomyosarcomas

Stage I Tumour limited to uterus
IA < 5cm
IB > 5cm
Stage II Tumour extends to the pelvis
IIA Adnexal involvement
IIB Tumour extends to extrauterine pelvic tissue
Stage III Tumour invades abdominal tissues (not just protruding into the abdomen)
IIIA One site
IIIB > One site
IIIC Metastasis to pelvic and/or para-aortic lymph nodes
Stage IV Tumour invades bladder and/or bowel mucosa, and/or distant metastases
IVA Tumour invades bladder and/or rectum
IVB Distant metastasis

Endometrial Stromal Sarcoma

Stage I Tumour limited to uterus
IA Tumour limited to endometrium/endocervix with no myometrial invasion
IB Less than or equal to half myometrial invasion
IC More than half myometrial invasion
Stage II Tumour extends to the pelvis
IIA Adnexal involvement
Stage III Tumour invades abdominal tissues (not just protruding into the abdomen)
IIIA One site
IIIB > One site
IIIC Metastasis to pelvic and/or para-aortic lymph nodes
Stage IV Tumour invades bladder and/or bowel mucosa, and/or distant metastases
IVA Tumour invades bladder and/or rectum
IVB Distant metastasis
Carcinosarcomas should be staged as carcinoma of endometrium
Simultaneous tumours of the uterine corpus and ovary/pelvis in association with ovarian/pelvic endometriosis should be classified as independent primary tumours

Spread patterns are local, haematogenous and lymphatic. MMT’s are more likely to spread via lymphatics (17%) than LMS (4%). At relapse LMS more likely to have distant component than MMT. LMS have a poorer prognosis than MMT.

Tend to occur in older woman. There appears no predisposing factors other than prior pelvic irradiation therapy and perhaps prolonged Tamoxifen use. Extrauterine spread at diagnosis is usually confined to pelvis involving the adnexa (23%), vagina (4%), parametria (13%), other pelvic structures (43%) and nodes (13%). Prognostic factors for MMT include: stage, myoinvasion, grade, LVSI, positive washings and serous and clear cell carcinomatous component. Features of the stromal component of the tumour including grade, mitotic index and presence and type soft heterologous elements are not related to risk or presence of metastases. They behave like poorly differentiated endometrial carcinomas. Locoregional recurrence alone occurs in 40% with median time to recurrence of 8 months and median survival after recurrence of 13 months.

Tend to occur in younger women with a median age 50. In apparent early stage disease, the ovaries are infrequent sites of metastases (3.5%). Prognostic factors for LMS are mitotic index, age and stage. The prognosis may be slightly better for those sarcomas arising within a fibroid. Median time to recurrence is 2 years. Up to 85% at relapse have a component of distant failure. Removal of retained ovaries has not been shown to affect survival.

Are very uncommon and initially comprised 3 distinct variants based on morphologic features, mitotic count and biologic behavior: (i) stromal nodule (ii) low grade endometrial stromal sarcoma (ESS) and (iii) high grade endometrial stromal sarcoma. Current classification is (i) endometrial stromal sarcoma and (ii) undifferentiated sarcoma. Apart from the stromal nodule, they are aggressive tumours and present with abnormal vaginal bleeding. Most involve the endometrium and are diagnosed by curettage. Low grade sarcomas tend to occur in premenopausal women and tend to be localized to the uterus at presentation. Nodal involvement is uncommon. While the overall recurrence rate of stage I patients is 50%, recurrence is more likely with tumors greater than 5cm that have venous invasion or parametrial extension, thus postoperative therapy warranted in these patients. Oophorectomy has been shown to reduce local recurrence.

Ideally surgery for MMT and ESS should comprise a THBSO to remove the primary tumour. Peritoneal washings, pelvic lymph node assessment and omental biopsy will help define the true extent of disease and provide valuable prognostic information. Such information may also be valuable in the decision making process for the need for further therapy. Surgical staging has been found to be a prognostic indicator for survival in MMT. Radical hysterectomy has not been found to improve survival.

For patients with LMS, the diagnosis is not often suspected preoperatively and most will have undergone a simple or type I hysterectomy without surgical staging. Lymph node spread for LMS is less common than for MMT (4% vs. 17%) and the decision to undertake surgical staging if the diagnosis is suspected preoperatively should be directed by the surgical oncologist. Removal of retained ovaries has not been shown to improve survival in LMS.

While not affecting long term survival, pelvic irradiation therapy has been shown to reduce the pelvic recurrence rate in MMT and ESS. We thus advocated pelvic irradiation therapy in most cases of MMT and ESS. LMS have been found to be relatively radioresistant. The affect of adjuvant pelvic irradiation in apparent early LMS is marginal, as most recurrences have a component of distant spread. Only 6% of early LMS will have pure pelvic failure. We do not advocate adjuvant pelvic irradiation for apparent early LMS.

In patients with advanced age and poor performance status a clinical decision not to offer adjuvant radiation therapy may be appropriate.

While no prospective randomised data exists showing a survival benefit for adjuvant chemotherapy, a GOG study of patients with apparent early staged uterine sarcoma’s randomised post hysterectomy to no further therapy or 6 cycles of adriamycin demonstrated decreased distant metastases, less recurrences and improved survival in the adriamycin treated patients. Due to poor patient accrual, the power of this study was unable however to demonstrate a statistical difference between both groups. All other series are small and retrospective, suffering from the usual biases. There is however retrospective/anecdotal evidence of a potential role for chemotherapy in leiomyosarcoma in reducing the distant failure rate.

Two randomized studies of adjuvant chemotherapy of adult soft tissue sarcomas of different sites reveal that single agent doxorubicin significantly improves survival. Other studies show no such benefit.

There is no evidence to demonstrate the superiority of combination chemotherapy over single agent chemotherapy for advanced and recurrent disease. Active agents include cisplatin, adriamycin, ifosfamide and Taxol . Taxol does not appear to have sufficient activity to warrant its use in uterine leiomyosarcoma.

In patients with advanced age and poor performance status a clinical decision not to offer adjuvant chemotherapy may be appropriate.

Due to the high distant failure rate we advocate adjuvant chemotherapy in all cases of MMT, LMS, and most high grade ESS.

Both MMT and LMS demonstrate oestrogen and progestogen receptors, but neither receptor status nor the use of hormonal agents (Provera or Tamoxifen) affect survival. Hormonal therapy is not recommended in their initial management.

In ESS, progestogen or tamoxifen therapy can be utilized. Knowledge of receptor status in this situation may be of benefit. For receptor negative patients, thought to be at high risk of distant relapse, Adriamycin or cisplatin chemotherapy may be employed.

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