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

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
Carcinoma of the Endometrium

6. Carcinoma of the Endometrium
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%)
-The vast majority of uterine cancers are carcinomas with most of those being endometrioid or adenosquamous histology
-These histologies carry a relatively good prognosis.
-about 5% of the carcinomas will be poor prognosis histologies like UPSC or clear cell carcinomas which spread in a more aggressively
-The sarcomas also tend to carry a poor prognosis, an they comprise about 6% of uterine corpus CA in the US, but are about 2X as common in black women as compared to whites. As a result the prevalence ratio in at Downstate is roughly 85/15 carcinoma to sarcoma.
*poor prognosis histology

8. Endometrial Cancer: Type I/II Concept
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
Among the endometrial carcinomas, it has become more common to distinguish between the type I vs type II tumors.
-The majority will fall into Type I- the classic Estrogen related cancer. E, younger, low grade, endometroid
-Type II refers to those tumors which appear unrelated to estrogen- generally the high grade tumors and poor prognosis histologies in women without classic risk factors.
-A third category of tumors are being recognized the genetic/familial cases like HNPCC (a defect in MSH mismatch repair genes) 40X risk of EM ca (5X Ov) pts as young as 16y/o

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
Other surgical principles are as follows:
If we are not certain preoperatively about the need for lymph node sampling we want to be sure to have frozen section available and a pathologist who can accurately evaluate the tumor for grade and depth of invasion as well to rule out as cervical involvement
If extrauterine disease is present we should be prepared to resect it

13. Endometrial Cancer: Nodal Involvement
Situation
% Positive Nodes
G1, inner 1/3 myometrial invasion, no extrauterine disease.
<1%
G2 or G3, inner 1/3 invasion, no extrauterine disease
5-9% Pelvic
4% Aortic
G3 with outer 1/3 invasion, and/or extrauterine disease
20-60% Pelvic
10-30% Aortic
-While the grade of the tumor may be known in advance of surgery, the depth of invasion cannot be accurately known until the uterus is removed.
-Because of the very low rate of lymph node metastases in patients with G1 tumors who have no or superficial myometrial invasion, LNS is not necessary and the risk from the procedure may outweigh the benefits
-LNS is currently advocated by most oncologists in all other circumstances although some controversy exists with respect to small non invasive or minimally invasive G2 tumors

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?
Most oncologists advocate some imaging test to estimate the depth of invasion and to look for the presence or absence of extrauterine disease prior to surgery
-The value of this preoperative information isn't totally clear
-It may be useful in deciding on an approach- abdominal vs. vaginal approach, and possibly in deciding simple vs. radical hysterectomy
-May be useful for the general gynecologist in deciding whether to refer to a gyn oncologist or just have someone on standby incase LN sampling is necessary

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*
As I alluded to, there is some controversy over Grade 2 tumors and whether they always need LNS.
Some oncologist have proposed that if the tumor is small (<2cm) & minimally invasive, then grade 2 tumors also can also avoid LNS
*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)
There is no contoversy that all Grade 3 regardless of depth of invasion
and all deeply invasive tumors regardless of grade, require complete surgical staging
*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):
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):
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.
A number of studies have looked at the feasibility of performing surgical treatment and staging via laparoscopy instead of via laparotomy.
These studies have typically shown:
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.
The GOG is currently undertaking a large multicenter prospective randomized trial to address these issues more rigorously. When completed the GOG trial will have recruited more than 2,500 patients and issues related to selection bias will have been reduced by the randomization process.

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 year survival
I %
II %
III %
IV %