17 per million women annually [Platz, & Benda, 1995]
Between 1989-1999, 2677 women were diagnosed with uterine sarcoma (Brooks et al, April, 2004)
prior pelvic radiation (10%-25% of cases)
3X increase in risk among black women (Brooks et al, April, 2004)
Data regarding parity and time of menarche and menopause as risk factors are inconclusive (Sherman & Devesa ,2003)
long-term adjuvant tamoxifen
An increase in the risk of uterine sarcomas appears to accompany the use of long-term adjuvant tamoxifen in women with breast cancer [Wickerham et al, 2002, Wysowski et al, 2002].
Since 1978, when tamoxifen was first marketed in the United States, 159 cases of uterine sarcoma worldwide have been reported
Histologic Classification Mixed mesodermal sarcoma Carcinosarcoma Mixed Liposarcoma (ii) Endometrial stromal sarcoma Osteosarcoma (i) endolymphatic stromal sarcoma Chondrosarcoma Stromal sarcoma Rhabdomyosarcoma Leimyosarcoma Pure Heterologous Homologous Type
GOG , 1993
Mixed mullerian sarcomas - 50%
Endometrial stromal sarcoma (15%)
Others (Adenosarcoma 5%)
Arise from smooth muscles of the uterus usually de novo
appear grossly as a large (>10 cm) yellow or tan solitary mass with soft, fleshy cut surfaces exhibiting hemorrhage and necrosis [Viereck et al, 2002].
Leiomyosarcoma: Low or high grade
Frequent mitotic figures
significant nuclear atypia,
presence of coagulative necrosis of tumor cells. [ Bell et al, 1994 ]
Endometrial stromal Sarcoma :
A pure homologous neoplasm
Subtypes: low and high grade
Low grade : slow growing tumors with infrequent metastasis or recurrence after therapy. [Oliva, et al, 2000].
high grade : enlarge and metastasize quickly and are often fatal.
Mixed mullerian sarcomas
Both carcinomatous and sarcomatous elements must be present in this type of sarcoma.
metastasize early in the course of the disease via hematogenous and lymphatic pathways
grows as a polypoidal mass with a broad base
homologous ( carcinosarcoma ) contain only tissue elements that are native to the uterus.
heterologous ( mixed mesodermal sarcoma ) contain tissue element that is foreign to the uterus.
both malignant stromal and benign epithelial components
a significantly increased occurrence of this tumor (Seidman et al, 1999)
present as polypoid masses
Vaginal bleeding is the most common presenting symptom of a uterine sarcoma.
On pelvic examination, the uterus is enlarged and, in some patients, part of the tumor may protrude from the uterine cavity through the cervical os.
Among 341 women with a rapidly growing uterus by clinical or ultrasound examination, only one (0.27 percent) had a uterine sarcoma . [Parker et al, 1994].
Should be considered in
postmenopausal women with a pelvic mass, abnormal bleeding, and pelvic pain, where the incidence of sarcoma is 1 to 2 percent [Leibsohn et al, 1990]
Ultrasound examination, MRI, or CT scan cannot reliably distinguish between a sarcoma, leiomyoma or endometrial cancer [Rha et al, 2003].
The diagnosis of uterine sarcomas is made from histologic examination of the entire uterus
Staging: surgical Sarcoma has spread outside the true pelvis IV Sarcoma has spread outside the uterus but is confined to the true pelvis III Sarcoma is confined to the corpus and cervix II Sarcoma is confined to the corpus I Description Stage based on FIGO staging for endometrial cancer
Lymph node Biopsy
patients with uterine sarcoma grossly confined to the uterus/cervix showed lymph node metastases in 5 of 101 patients
should be reserved for women with clinically suspicious nodes [Leitao et al, 2003 ]
In one series of 208 women with uterine leiomyosarcoma, only four of 36 who underwent lymph node sampling had positive nodes [Giuntoli et al, 2003].
because of their rarity, uterine sarcomas are not suitable for screening. (Levenback, 1996)
is the only curative therapy for uterine sarcomas [Morice et al, 2003]
Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy).
Surgery plus adjuvant chemotherapy.
Surgery plus adjuvant irradiation
Is it beneficial !!
Interpretation of the possible benefit of different modalities is hampered by the difficulty in comparing outcomes from series in which patients of varying stages and histologies were reported
The five year survivals
Surgery alone (46 %)
Surgery and radiotherapy (62 %)
Surgery and chemotherapy (43 %)
Radiation alone (8 %)
Weitmann et al, 2001
three-year local recurrence rates
No adjuvant treatment 62 %
Whole pelvis external beam radiation therapy 31 %
Chemotherapy alone 71 percent
[Livi et al, 2003]
Massachusetts General Hospital
Adjuvant therapy after optimal cytoreduction does not decrease the rate of recurrence [Dinh et al, 2004]
Adjuvant radiation therapy
Some studies of postoperative radiation suggest a survival benefit [Moskovic et al, 1993 Knocke et al, 1998, Weitmann et al, 2001].
Other studies showed cure rate was similar for those treated with surgery alone or followed by radiation, regardless of the stage of disease [Giuntoli et al, 2003]
Complications of Radiation Tx:
Cystitis (a/w UTI)
Current studies consist primarily of Phase II chemotherapy trials for advanced disease
The role of chemotherapy in the treatment of uterine sarcomas has been limited
This is because
Adjuvant chemotherapy following complete resection (stage I and II) has not been established to be effective in RCT
But some nonrandomized trials have reported improved survival following adjuvant chemotherapy with or without radiation therapy Piver et al, 1988 ,van Nagell , et al, 1986, Peters et al, 1989
doxorubicin is an effective drug for advanced leiomyosarcoma
combinations with doxorubicin increase the objective response rate but add substantial toxicity
A very recent small trial showed promising results with gemcitabine plus docetaxel [Hensley et al, 2002].
benefit from cisplatin-based chemotherapy particularly combinations of cisplatin with doxorubicin and ifosfamide, or single agent paclitaxel [ Gallup et al, 2003 , van Rijswijk et al, 2003, Harris et al, 2003]
Mixed mesodermal tumors
Cisplatin and ifosfamide appear to have greater activity than does doxorubicin alone [Ramondetta et al, 2003].
In a very small uncontrolled trial : cisplatin, doxorubicin, and dacarbazine give three year survivals of 51 % [Baker et al, 1991].
Estrogen and/or progesterone receptors are present in leiomyosarcomas and endometrial stromal sarcomas but do not predict hormone responsiveness.
In fact, only one of 28 patients with residual or recurrent disease following surgery had an objective response to hormone therapy (Wade 1994)
Most relapses occur in the pelvis, followed by lung and abdomen
currently no standard therapy for patients with recurrent disease
Doxorubcin in leiomyosarcoma ?
Cisplatin in carcinosarcoma ?
In a recent RCT 2000
ifosfamide with or without cisplatin for recurrent sarcoma
demonstrated a higher response rate on the combination arm
However,use of the combination was not justified because of increased toxic effects [Sutton et al, 2000]
the 5-year survival : stage I less than 50%
remaining stages : 0% to 20%.
strongest predictor of survival was menopausal status at time of diagnosis
[Major et al, 1993]
age over 50 years was a poor prognostic factor, as was size greater than 5 cm [Giuntoli et al, 2003].
Aggressive surgical cytoreduction at the time of initial diagnosis offers the best survival
More RCTs are needed to determine the value and regime of adjuvant therapy