1. Prof Greta Dreyer University of Pretoria
Uterine Sarcoma
Prof Greta Dreyer
University of Pretoria

2. Challenging Rare → Limited data
Rapidly growing (doubling time is 4 weeks)
Incidence appears to be increasing

3. Epidemiology Rare 2% to 5% of all uterine malignancies
17 per million women annually [Platz, & Benda, 1995]

4. Risk Factors 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)

5. 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].

6. Histologic Classification
Heterologous
Homologous
Type
Rhabdomyosarcoma
Leimyosarcoma
Pure
Chondrosarcoma
Stromal sarcoma
Osteosarcoma
(i) endolymphatic stromal sarcoma
Liposarcoma
(ii) Endometrial stromal sarcoma
Mixed mesodermal sarcoma
Carcinosarcoma
Mixed

7. GOG , 1993 Mixed mullerian sarcomas - 50% Leiomyosarcoma (30%).
Endometrial stromal sarcoma (15%)
Adenosarcoma (5%)

8. Leiomyosarcoma (30%)
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].

9. Leiomyosarcoma

10. Leiomyosarcoma: Low or high grade
Frequent mitotic figures
significant nuclear atypia,
presence of coagulative necrosis of tumor cells. [Bell et al, 1994 ]

11. Zaloudek & Norris classification

12. Endometrial stromal tumors :
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.

13. Mixed malignant 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

14. Mixed malignant mullerian sarcomas
Mixed müllerian homologous sarcomas (carcinosarcoma) contain only tissue elements that are endogenous to the uterus.
In contrast, if exogenous tissue is present (eg, bone, cartilage, fat), the tumor should be classified as a mixed heterologous müllerian sarcoma (mixed mesodermal sarcoma).

15. Carcinosarcoma or MMMT

16. Adenosarcoma both malignant stromal and benign epithelial components
a significantly increased occurrence of this tumor (Seidman et al, 1999)
present as polypoid masses

17. Clinical Diagnosis
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.

18. Rapidly growing
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].

19. 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]

20. Evaluation
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

21. Staging: Description Stage I II III IV
based on FIGO staging for endometrial cancer
Description
Stage
Sarcoma is confined to the corpus I
Sarcoma is confined to the corpus and cervix II
Sarcoma has spread outside the uterus but is confined to the true pelvis
III
Sarcoma has spread outside the true pelvis IV

22. Lymph node dissection
patients with uterine sarcoma grossly confined to the uterus/cervix showed lymph node metastases in 5 of 101 patients
should be done in all women who can tolerate the procedure?? / with clinically suspicious nodes?? [Leitao et al, 2003 ]

23. Further support
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].

24. Screening
because of their rarity, uterine sarcomas are not suitable for screening. (Levenback, 1996)

25. Surgery
is the only curative therapy for uterine sarcomas [Morice et al, 2003]

26. Modalities
Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy).
Surgery plus adjuvant chemotherapy.
Surgery plus adjuvant irradiation

27. 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

28. The five year survivals
Surgery alone (46 %)
Surgery and radiotherapy (62 %)
Surgery and chemotherapy (43 %)
Radiation alone (8 %)
Weitmann et al, 2001

29. The three-year local recurrence rates
 No adjuvant treatment 62 %
 Whole pelvis external beam radiation therapy 31 %
Chemotherapy alone 71 percent
[Livi et al, 2003]

30. Adjuvant radiation therapy
The value of pelvic radiation is not established
Some studies of postoperative radiation suggest a survival benefit [Moskovic et al, 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]

31. Complications of Radiation Tx:
Acute:
Fever
Perforation
Diarrhea
Bladder spasm
Chronic:
Fistula
Enteritis
Cystitis (a/w UTI)
Proctitis

32. Adjuvant chemotherapy
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

33. Adjuvant therapy
Adjuvant chemotherapy following complete resection (stage I and II) has not been established to be effective in a randomized trial
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

34.   Leiomyosarcoma
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].

35.   Carcinosarcoma
Women with carcinosarcoma may 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]

36. 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].

37. Hormone therapy
Estrogen, progesterone, and other hormone 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

38. Recurrent Disease
Most relapses occur in the pelvis, followed by lung and abdomen
currently no standard therapy for patients with recurrent disease

39. 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]

40. Prognosis poor prognosis 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]

41. leiomyosarcoma
age over 50 years was a poor prognostic factor, as was size greater than 5 cm [Giuntoli et al, 2003].

42. Conclusion
Aggressive surgical cytoreduction at the time of initial diagnosis offers the best survival

43. Thank You