Uterine sarcoma

1. Uterine Sarcoma

2. Challenging
Rare → Limited data
Rapidly growing (doubling time is 4 weeks)
tend to be increasing (Nordal & Thoresen 1997)

3. Epidemiology
Rare
2% to 5% of all uterine malignancies
17 per million women annually [Platz, &
Benda, 1995]
Between 1989-1999, 2677 women were
diagnosed with uterine sarcoma (Brooks et al,
April, 2004)

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].
Since 1978, when tamoxifen was first
marketed in the United States, 159 cases of
uterine sarcoma worldwide have been
reported

6. Histologic Classification
Mixed mesodermal
sarcoma
CarcinosarcomaMixed
Liposarcoma(ii) Endometrial stromal sarcoma
Osteosarcoma(i) endolymphatic stromal sarcoma
ChondrosarcomaStromal sarcoma
RhabdomyosarcomaLeimyosarcomaPure
HeterologousHomologousType

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

8. Leiomyosarcoma
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. 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.

12. 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

13. Subdivided
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.

14. MMT

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

16. 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.

17. !!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].

18. 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]

19. 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

20. Staging: surgical
Sarcoma has spread outside the true pelvisIV
Sarcoma has spread outside the uterus but is confined to the
true pelvis
III
Sarcoma is confined to the corpus and cervixII
Sarcoma is confined to the corpusI
DescriptionStage
based on FIGO staging for endometrial cancer

21. 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 ]

22. 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].

23. Treatment
because of their rarity, uterine sarcomas are
not suitable for screening. (Levenback, 1996)

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

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

26. !! 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

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

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

29. Massachusetts General Hospital
1990-1999
Adjuvant therapy after optimal cytoreduction
does not decrease the rate of recurrence
[Dinh et al, 2004]

30. 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]

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

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. 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

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
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 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)

38. Recurrent Disease
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 ?

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
More RCTs are needed to determine the
value and regime of adjuvant therapy

43. Thank You