Uterine sarcoma


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Uterine sarcoma

  1. 1. Uterine Sarcoma
  2. 2. Challenging <ul><li>Rare -> Limited data </li></ul><ul><li>Rapidly growing (doubling time is 4 weeks) </li></ul><ul><li>tend to be increasing (Nordal & Thoresen 1997) </li></ul>
  3. 3. Epidemiology <ul><li>Rare </li></ul><ul><li>2% to 5% of all uterine malignancies </li></ul><ul><li>17 per million women annually [Platz, & Benda, 1995] </li></ul><ul><li>Between 1989-1999, 2677 women were diagnosed with uterine sarcoma (Brooks et al, April, 2004) </li></ul>
  4. 4. Risk Factors <ul><li>prior pelvic radiation (10%-25% of cases) </li></ul><ul><li>3X increase in risk among black women (Brooks et al, April, 2004) </li></ul><ul><li>Data regarding parity and time of menarche and menopause as risk factors are inconclusive (Sherman & Devesa ,2003) </li></ul>
  5. 5. long-term adjuvant tamoxifen <ul><li>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]. </li></ul><ul><li>Since 1978, when tamoxifen was first marketed in the United States, 159 cases of uterine sarcoma worldwide have been reported </li></ul>
  6. 6. 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
  7. 7. GOG , 1993 <ul><li>Mixed mullerian sarcomas - 50% </li></ul><ul><li>homologous heterologous </li></ul><ul><li>Leiomyosarcoma (30%). </li></ul><ul><li>Endometrial stromal sarcoma (15%) </li></ul><ul><li>Others (Adenosarcoma 5%) </li></ul>
  8. 8. Leiomyosarcoma <ul><li>Arise from smooth muscles of the uterus usually de novo </li></ul><ul><li>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]. </li></ul>
  9. 9. Leiomyosarcoma
  10. 10. Leiomyosarcoma: Low or high grade <ul><li>Frequent mitotic figures </li></ul><ul><li>significant nuclear atypia, </li></ul><ul><li>presence of coagulative necrosis of tumor cells. [ Bell et al, 1994 ] </li></ul>
  11. 11. Endometrial stromal Sarcoma : <ul><li>A pure homologous neoplasm </li></ul><ul><li>Subtypes: low and high grade </li></ul><ul><li>Low grade : slow growing tumors with infrequent metastasis or recurrence after therapy. [Oliva, et al, 2000]. </li></ul><ul><li>high grade : enlarge and metastasize quickly and are often fatal. </li></ul>
  12. 12. Mixed mullerian sarcomas <ul><li>Both carcinomatous and sarcomatous elements must be present in this type of sarcoma. </li></ul><ul><li>metastasize early in the course of the disease via hematogenous and lymphatic pathways </li></ul><ul><li>grows as a polypoidal mass with a broad base </li></ul>
  13. 13. Subdivided <ul><li>homologous ( carcinosarcoma ) contain only tissue elements that are native to the uterus. </li></ul><ul><li>heterologous ( mixed mesodermal sarcoma ) contain tissue element that is foreign to the uterus. </li></ul>
  14. 14. MMT
  15. 15. Adenosarcoma <ul><li>both malignant stromal and benign epithelial components </li></ul><ul><li>a significantly increased occurrence of this tumor (Seidman et al, 1999) </li></ul><ul><li>present as polypoid masses </li></ul>
  16. 16. Clinical Diagnosis <ul><li>Vaginal bleeding is the most common presenting symptom of a uterine sarcoma. </li></ul><ul><li>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. </li></ul>
  17. 17. Rapidly growing!! <ul><li>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]. </li></ul>
  18. 18. Should be considered in <ul><li>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] </li></ul>
  19. 19. Evaluation <ul><li>Ultrasound examination, MRI, or CT scan cannot reliably distinguish between a sarcoma, leiomyoma or endometrial cancer [Rha et al, 2003]. </li></ul><ul><li>The diagnosis of uterine sarcomas is made from histologic examination of the entire uterus </li></ul>
  20. 20. 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
  21. 21. Lymph node Biopsy <ul><li>patients with uterine sarcoma grossly confined to the uterus/cervix showed lymph node metastases in 5 of 101 patients </li></ul><ul><li>should be reserved for women with clinically suspicious nodes [Leitao et al, 2003 ] </li></ul>
  22. 22. Further support <ul><li>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]. </li></ul>
  23. 23. Treatment <ul><li>because of their rarity, uterine sarcomas are not suitable for screening. (Levenback, 1996) </li></ul>
  24. 24. Surgery <ul><li>is the only curative therapy for uterine sarcomas [Morice et al, 2003] </li></ul>
  25. 25. Modalities <ul><li>Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy). </li></ul><ul><li>Surgery plus adjuvant chemotherapy. </li></ul><ul><li>Surgery plus adjuvant irradiation </li></ul>
  26. 26. Is it beneficial !! <ul><li>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 </li></ul>
  27. 27. The five year survivals <ul><li>Surgery alone (46 %) </li></ul><ul><li>Surgery and radiotherapy (62 %) </li></ul><ul><li>Surgery and chemotherapy (43 %) </li></ul><ul><li>Radiation alone (8 %) </li></ul><ul><li>Weitmann et al, 2001 </li></ul>
  28. 28. three-year local recurrence rates <ul><li>  No adjuvant treatment 62 % </li></ul><ul><li>  Whole pelvis external beam radiation therapy 31 % </li></ul><ul><li>Chemotherapy alone 71 percent </li></ul><ul><li>[Livi et al, 2003] </li></ul>
  29. 29. Massachusetts General Hospital <ul><li>1990-1999 </li></ul><ul><li>Adjuvant therapy after optimal cytoreduction does not decrease the rate of recurrence [Dinh et al, 2004] </li></ul>
  30. 30.    Adjuvant radiation therapy <ul><li>Some studies of postoperative radiation suggest a survival benefit [Moskovic et al, 1993 Knocke et al, 1998, Weitmann et al, 2001]. </li></ul><ul><li>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] </li></ul>
  31. 31. Complications of Radiation Tx: <ul><li>Acute: </li></ul><ul><li>Perforation </li></ul><ul><li>Fever </li></ul><ul><li>Diarrhea </li></ul><ul><li>Bladder spasm </li></ul><ul><li>Chronic: </li></ul><ul><li>Proctitis </li></ul><ul><li>Cystitis (a/w UTI) </li></ul><ul><li>Fistula </li></ul><ul><li>Enteritis </li></ul>
  32. 32. Adjuvant chemotherapy <ul><li>Current studies consist primarily of Phase II chemotherapy trials for advanced disease </li></ul><ul><li>The role of chemotherapy in the treatment of uterine sarcomas has been limited </li></ul>
  33. 33. This is because <ul><li>Adjuvant chemotherapy following complete resection (stage I and II) has not been established to be effective in RCT </li></ul><ul><li>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 </li></ul>
  34. 34.    Leiomyosarcoma <ul><li>doxorubicin is an effective drug for advanced leiomyosarcoma </li></ul><ul><li>combinations with doxorubicin increase the objective response rate but add substantial toxicity </li></ul><ul><li>A very recent small trial showed promising results with gemcitabine plus docetaxel [Hensley et al, 2002]. </li></ul>
  35. 35.    Carcinosarcoma <ul><li>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] </li></ul>
  36. 36. Mixed mesodermal tumors <ul><li>Cisplatin and ifosfamide appear to have greater activity than does doxorubicin alone [Ramondetta et al, 2003]. </li></ul><ul><li>In a very small uncontrolled trial : cisplatin, doxorubicin, and dacarbazine give three year survivals of 51 % [Baker et al, 1991]. </li></ul>
  37. 37. Hormone therapy <ul><li>Estrogen and/or progesterone receptors are present in leiomyosarcomas and endometrial stromal sarcomas but do not predict hormone responsiveness. </li></ul><ul><li>In fact, only one of 28 patients with residual or recurrent disease following surgery had an objective response to hormone therapy (Wade 1994) </li></ul>
  38. 38. Recurrent Disease <ul><li>Most relapses occur in the pelvis, followed by lung and abdomen </li></ul><ul><li>currently no standard therapy for patients with recurrent disease </li></ul><ul><li>Doxorubcin in leiomyosarcoma ? </li></ul><ul><li>Cisplatin in carcinosarcoma ? </li></ul>
  39. 39. In a recent RCT 2000 <ul><li>ifosfamide with or without cisplatin for recurrent sarcoma </li></ul><ul><li>demonstrated a higher response rate on the combination arm </li></ul><ul><li>However,use of the combination was not justified because of increased toxic effects [Sutton et al, 2000] </li></ul>
  40. 40. Prognosis <ul><li>poor prognosis </li></ul><ul><li>the 5-year survival : stage I less than 50% </li></ul><ul><li>remaining stages : 0% to 20%. </li></ul><ul><li>strongest predictor of survival was menopausal status at time of diagnosis </li></ul><ul><li>[Major et al, 1993] </li></ul>
  41. 41. leiomyosarcoma <ul><li>age over 50 years was a poor prognostic factor, as was size greater than 5 cm [Giuntoli et al, 2003]. </li></ul>
  42. 42. Conclusion <ul><li>Aggressive surgical cytoreduction at the time of initial diagnosis offers the best survival </li></ul><ul><li>More RCTs are needed to determine the value and regime of adjuvant therapy </li></ul>
  43. 43. Thank You