Uterine Sarcoma

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Uterine Sarcoma

• Hesham Al-Inany, MD
• Cairo University

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Challenging

• Rare ? Limited data
• Rapidly growing (doubling time is 4 weeks)
• tend to be increasing

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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)

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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)

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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.

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Histologic Classification
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GOG , 1993

• Mixed mullerian sarcomas - 50
• Leiomyosarcoma (30).
• Endometrial stromal sarcoma (15)
• Adenosarcoma (5)

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Leiomyosarcoma

• Arise from smooth muscles of the uterus usually
  de novo
• appear grossly as a large (gt10 cm) yellow or tan
  solitary mass with soft, fleshy cut surfaces
  exhibiting hemorrhage and necrosis Viereck et
  al, 2002.

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Leiomyosarcoma
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Leiomyosarcoma Low or high grade

• Frequent mitotic figures
• significant nuclear atypia,
• presence of coagulative necrosis of tumor cells.
  Bell et al, 1994

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Zaloudek Norris classification
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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.

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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

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• Mixed müllerian homologous sarcomas
  (carcinosarcoma) contain only tissue elements
  that are indigenous to the uterus.
• In contrast, if exogenous tissue not normally
  found in the uterus is present (eg, bone,
  cartilage), the tumor should be classified as a
  mixed heterologous müllerian sarcoma (mixed
  mesodermal sarcoma).

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MMT
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Adenosarcoma

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

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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.

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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.

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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

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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

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Staging surgical
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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

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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.

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Treatment

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

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Surgery

• is the only curative therapy for uterine sarcomas
  Morice et al, 2003

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Modalities

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

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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

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The five year survivals

• Surgery alone (46 )
• Surgery and radiotherapy (62 )
• Surgery and chemotherapy (43 )
• Radiation alone (8 )
• Weitmann et al, 2001

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three-year local recurrence rates

•  No adjuvant treatment 62
•  Whole pelvis external beam radiation therapy 31
  
• Chemotherapy alone 71 percent
• Livi et al, 2003

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Massachusetts General Hospital

• 1990-1999
• Adjuvant therapy after optimal cytoreduction does
  not decrease the rate of recurrence Dinh et al,
  February, 2004

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  Adjuvant radiation therapy

• The value of pelvic radiation is not established
• 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

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Complications of Radiation Tx

• Acute
• Perforation
• Fever
• Diarrhea
• Bladder spasm

• Chronic
• Proctitis
• Cystitis (a/w UTI)
• Fistula
• Enteritis

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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

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However

• 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

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  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.

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  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

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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.

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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

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Recurrent Disease

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

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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

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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

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leiomyosarcoma

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

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Conclusion

• Aggressive surgical cytoreduction at the time of
  initial diagnosis offers the best survival

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Thank You