Philippe Van Trappen, MD PhD Gynaecologie/Oncologie

1. Gynaecologische Tumoren:Internationale richtlijnen en Nieuwe perspectieven indiagnostiek en behandeling • Philippe Van Trappen, MD PhD • Gynaecologie/Oncologie SYMPOSIUM ONCOLOGIE – 7 JUNI 2008

2. Venous Spread This pathway might account for the occasional appearance of a low vaginal metastasis; but venous spread is not a common feature of uterine cancer.

3. Lymphatic Spread The incidence of this (it is much debated) seems to be somewhere between 10 and 30%. All pelvic nodes, including the internal iliacs, the parametrium, the ovaries, and the vagina may be involved, probably with equal frequency. Lymphatic spread is more likely to occur when the tumour is anaplastic and the uterine wall is deeply invaded.

4. Tubal Spread Malignant cells can pass along the tube in the same way that peritoneal spill may occur during menstruation. This may account for isolated ovarian metastases.

5. Carcinoma of the Endometrium

6. Carcinoma of the Endometrium

7. Cancers of the Uterine Corpus:Histologic Types • Carcinoma (94%) • Endometrioid (87%) • Adenosquamous (4%) • Papillary Serous* (3%) • Clear Cell* (2%) • Mucinous (1%) • Other (3%) • Sarcoma (6%) • Carcinosarcoma* (60%) • Leiomyosarcoma* (30%) • Endometrial Stromal Sarcoma (10%) • Adenosarcoma (<1%) *poor prognosis histology

8. Endometrial Cancer:Type I/II Concept • Type I • Estrogen Related • Younger and heavier patients • Low grade • Background of Hyperplasia • Perimenopausal • Exogenous estrogen • Type II (~10% of total cases) • Aggressive • High grade • Unfavorable Histology • Unrelated to estrogen stimulation • Occurs in older & thinner women • Familial/genetic (~15% of total cases) • Lynch II syndrome/HNPCC • Familial trend

9. Endometrial Cancer –diagnosis & assessment • Endometrial biopsy • – outpatient sampling (pipelle aspirate) • – hysteroscopy and curettage • Ultrasound: thickened endometrium/abnormal areas within cavity • or wall of womb • Doppler demonstration of abnormal endometrial vascularity • MRI: • imaging of pelvic/paraaortic lymph nodes and myometrial • invasion • PET-CT • (high sensitivity in detecting distant metastases; • high NPV in predicting LN metastases) • Park et al, 2008, Gynecol Oncol

10. IA: Tumor limited to endometrium • IB: Invasion to no more than half the myometrial thickness. • IC: Invasion to more than half the myometrial thickness • IIA: Invasion to the mucosa of the cervix. • IIB: Invasion to cervical stroma.

11. IIIA: Tumor invades serosa and/or adnexa,and/or positive peritoneal • cytology • IIIB: Vaginal metastases • IIIC: Metastases to pelvic and/or para-aortic lymph nodes. • IVA Tumor invasion of bladder and/or bowel mucosa. • IVB: Distant metastases including intra-abdominal metastases • and/or inguinal lymph nodes.

12. Endometrial Cancer: Intra-operative Surgical Principals • Availability of frozen section to determine the extent of staging procedure. • Capability of complete surgical staging • Capability of tumor reduction if indicated

13. Endometrial Cancer: Nodal Involvement

14. Endometrial Cancer -1.treatment • Usually surgical • Simple hysterectomy • (Laparoscopic) • and removal of tubes/ovaries only for • well differentiated stage Ia ~ 70% • Stage Ib/Ic, mod/poorly differentiated and poor prognostic types also require • pelvic/paraaortic lymph node sampling • (FIGO, ACOG) • Uterine Serous Papillary Carcinoma (USPC): • staging like ovarian cancer • Stage II • - radical hysterectomy or simple hysterectomy + RT • Stage III/IV • - cytoreductive surgery (>palliative for bleeding, bladder and • bowel involvement) • Primary radiotherapy is rarely used Carcinoma of the Endometrium

15. Uterine Cancer: Pre-op Evaluation • Transvaginal U/S? • CT Scan? • MRI?

16. Endometrial Cancer: Surgical Approach • TAH-BSO/washings only • Endometrioid* • Grades 1 and < 50% myometrial invasion* • or Grade 2 and no or minimal invasion and < 2 cm tumor diameter* *Verified via frozen section

17. Endometrial Cancer: Surgical Approach • Complete Surgical Staging* • All Grade 3 • Any > 50% myometrial invasion • Any >2 cm tumor diameter • All Serous/clear cell subtype** • Pre operative assessment of advanced disease (gross cervical or vaginal dz, etc) *TAH-BSO, washings, lymphadenectomy **omental/peritoneal biopsy

18. Laparoscopic Staging: Magrina JF, Weaver AL. Laparoscopic treatment of endometrial cancer: five-year recurrence and survival rates. Eur J Gynaecol Oncol. 2004;25(4):439-41. Holub Z, Jabor A, Bartos P, Eim J, Urbanek S, Pivovarnikova R. Laparoscopic surgery for endometrial cancer: long-term results of a multicentric study. Eur J Gynaecol Oncol. 2002;23(4):305-10. GOG LAP2 Protocol: Randomized study of Total Hysterectomy, BSO and Staging via Laparotomy vs. Laparoscopy- study still open • Previous studies show: • Similar blood loss • Same incidence of complications • Low incidence of conversion of laparoscopy to laparotomy • Longer operative times for laparoscopy (160 min vs. 115min) • Shorter hospital stay (4 vs 7 days) for laparoscopy • No difference in recurrence risk.

19. PROGNOSIS OF ENDOMETRIAL CARCINOMA With the exception of stage 1 tumors of histological grades I and II, the prognosis is less favourable than many gyaecologists believe，with an overall 5 year survival of 70％ approximately．Fortunately over 80％of cases are dagnosed at stage 1．

20. Stage 5 year survival I 85% II 68% III 42% IV 22%