Protocol Endometrial Cancer

Protocol Endometrial Cancer
1. General
2. Screening
3. Diagnosis
4. Surgical treatment
5. Adjuvant treatment
6. Follow up
7. Recurrences
8. Metastases

1. General
Endometrial cancer is the most common gynecologic malignancy in the Western world. In the USA there were in 2003 40 100 new cases. Factors influencing its prominence are the declining incidence of cervical cancer, prolonged life expectancy, earlier diagnosis and the increasing incidence of obesity. Currently endometrial cancer is the fourth most common tumor in women, ranking behind breast, bowel and lung cancers, and the seventh cause of death from malignancy in women. Endometrial cancer is a tumor of women in the postmenopause, although still 4% of the patients are younger than 40 years of age.

In 75% of all cases, the tumor is confined to the uterine corpus at the time of diagnosis.
Uncorrected 5-years survival rates of 75% can be expected.

Most cases of endometrial carcinoma are sporadic. Some cases have a hereditary basis: HNPCC families.

Environmental factors seem to be important. The increasing incidence of endometrial cancer has been attributed to an aging population and to dietary and hormonal factors. Obesity, unopposed estrogen and Tamoxifen for more than one year have been identified as risk factors. This is also the case for hormonal disturbances associated with diabetes mellitus, polycystic ovarian syndrome, and estrogen producing tumors.

Parity and oral contraceptives protect against endometrial cancer.
2. Screening:
There is no effective screening strategy.

3. Diagnosis
Anamnesis:
- Abnormal vaginal blood loss
- Fluor
- Micturation/defaecation
- Pain, weight loss, general health

Family:
Ask for colon, rectal, endometrial carcinoma’s and the age of onset. Also ask for other malignancies.
Physical examination:
- Weight, length, general condition
- Heart, lungs, abdomen
- Pelvic examination
- Lymph nodes inguinal, supraclavicular

Laboratory:
- Pap smear
- Routine preoperative blood chemistry and morphology

Immaging:
- X-thorax
- Transvaginal ultrasound
- CT scan/MRI: only on indication (suspicious for extrauterine disease)
- Cystoscopy and rectoscopy: in cases with voiding and/or defaecation problems.

Pathology:

Histology is needed for the diagnosis endometrial cancer. A tissue sample from the uterine cavity for diagnosis can be obtained in the outpatient office with an endometrium sample system (Pipelle, Vabra, Probette, Milex). This sampling can be done without anaesthesia after the vaginal ultrasound and/or the saline infusion ultrasound. An alternative approach is a hysteroscopy with biopsies of the endometrium under direct vision. In both instances sampling od tissue from the endocervical canal must be performed to rule out macroscopic endocervical involvement. However, the sensitivity of this procedure is low.

If these techniques are not available, a fractionated curettage can be performed.
The report of the pathologist has to include:

- Histologic cell type
- Grade

Advise: Every patient with unfavourable prognostic factors (high risk) or stage II or more needs to be discussed with a gynecologic oncologist and preferrsbly refered to a gynecologic oncology center hospital.

4. Surgical treatment
Clinical stage I:

Total abdominal hysterectomy with bilateral salpingo-oophorectomy.
- Median laparotomy
- Peritoneal washing: aspirate fluid or wash with 20-50 cc saline, aspirate and add 2 drips of heparine to the fluid to prevent clotting.
- Clamps on the tubal corners to prevent tumor spill during uterine manipulation.
- Inspection and palpation of uterus, adnexa, all serosal surfaces, lymph nodes in pelvis and para-aortic.
- Biopsie all suspected areas.
- TAH – BSO.
- Pelvic and lower periaortic lymphadenectomy in high risk patients: lymph nodes have to be removed from the external iliac and lower common iliac area, the obturator fossa, the para-aortic area and pre-caval area between bifurcation and inferior mesenteric artery.

Clinical stage IIa: macroscopic involvement of the cervical canal.
- Radical hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy.
- Lower periaortic lymphadenectomy in case of suspicious nodes.

Clinical stage III:
- Laparotomy and resection of tumor if possible.
- If not: radiotherapy and resection in case the tumor becomes respectable.

Clinical stage IV:
Individualization of treatment based on extension of disease.
After primary treatment and the result of pathological examination, the surgical stage can be determined.

5. Adjuvant treatment
Adjuvant treatment in surgical stage I:
External radiation is directed towards the operation field, parametria, top of vagina, regional lymph nodes.
Based on the PORTEC I study there are 3 risk factors in stage I disease:

- Age =>60 years
- Grade III
- Myometrium invasion > ½ of the myometrium

When 2 of these 3 factors are positive adjuvant radiotherapy is indicated.

Based on the PORTEC-2 study radiotherapy in stage 1-2a will be vaginal brachytherapy. External beam radiation will be given to the high risk group.

In cases where a lymphadenectomy has been performed and where the pathology of the nodes is negative for tumor, adjuvant brachytherapy on the top of the vagina has to be given.

Surgical stage II:
Stage IIA after TAH-BSO with occult tumor growth into the cervix: idem stage 1.
Stage IIA after radical hysterectomy and BSO: only radiotherapy if tumor growth into parametrium, tumor in cutting margins, tumor positive lymph nodes. If the vaginal margin is not free of tumor or tumor free margin < 5 mm: vaginal brachytherapy.

Surgical stage III and IV:
External radiotherapy and vaginal brachytherapy. Extended field irradiation in cases of para-aortic lymph node metastases.

Chemotherapy:
Still experimental. Cisplatin, Paclitaxel with or without Doxyrubicin are frequently tested and seem to be promising.

6. Follow-up:

First year: every 3 months
Second year: every 4 months
Third-fifth year: every 6 months
After 5 years: every year up to 10 years.

Most recurrences occur within 3 years.

Follow-up includes:
- Carefull medical history
- Pelvic examination: visual inspection of the top of the vagina and pelvic palpation.

Routine cytology of the top of the vagina is not necessary and does not contribute to the diagnosis of a recurrence.

7. Recurrences
Recurrences can be local: in the top of the vagina, or regional in the pelvis, or combined.
Vaginal discharge or blood loss after intercourse is often the first symptom of a vaginal recurrence.

In case of a recurrence the following protocol is indicated:

- General examination
- Pelvic examination
- CT scan thorax and abdomen
- Haematology, blood chemistry, CA 125
- Cystoscopy, rectoscopy, bone scan on indication

Treatment local recurrence:
Non radiated area:

Local radiotherapy. 80% complete remission.

Local recurrence > 2 cm: surgical excision before radiotherapy
Radiated area: exenteration in oncology clinic by gynecologic oncologist. Only indicated if distant metastases are ruled out.

Treatment regional recurrence: radiotherapy, eventually combined with surgery, individualization of treatment.
In patients with well differentiated tumors hormonal therapy with high dose progesterone can be indicated, especially if surgery and radiotherapy are not possible.

Distant metastases:
Mostly located in:
- Supraclavicular lymph nodes
- Lung
- Abdomen
- Liver
- Bone

Always try to get cytological (FNA) or histological confirmation.
Treatment: first choice is radiotherapy. If this is no option: individualize.

Referensi
Dutch School - Gynaecologic Oncology & Pelvic Surgery