Gynaecology Dr. Rozhan Lecture 6 CARCINOMA OF THE ENDOMETRIUM One of the commonest gynecological cancers,especially in white Americans. It is a disease of postmenopausal women with a peak incidence in the 6 th & 7 th decade of life it occurs most often in postmenopausal women(up to 80%of cases)with less than 5% diagnosed under 40 years of age. Screening: There is no effective screening programme, but occasionally cervical smears contain endometrial cancer cells or double thickness endometrial ultrasonic thickness of 4mm or more indicates a need for endometrial sampling. Risk Factors of endometrial ca.: 1. The actual cause of this cancer is unknown (idiopathic). 2. Estrogen - Early menarche < 12 Y - Late menopause > 52 Y - given estrogen alone as postmenopausal hormone replacement therapy. 3. Estrogen secreting tumors of the ovary are associated with an increased incidence of endometrial carcinoma. 4. Nulliparity and PCO syndrome(with defective progesterone synthesis)carry an increased risk. 5. obese,diabetic and hypertensive women develop endometrial cancer. 6. High risk in women with breast, ovarian (endometrial type) & colorectal Ca. 7. Previous pelvic radiation therapy 8. Family Hx of endometrial Ca 9. The endometrial hyperplasia induced by Tamoxifen produces endometrial polyp suggested a four-fold increase in endometrial carcinoma. Risk factors for endometrial cancer: Obesity mpaired carbohydrate tolerance Nulliparity Late menopause Unopposed oestrogen therapy Functioning ovarian tumours Previous pelvic irradiation Family history of carcinoma of breast, ovaryor colon 1
Protection for endometrial CA. 1. Oral contraception,especially after long term use.reduces incidence of both endometrial and ovarian carcinomas). 2. Cigarette smoking has also been associated with the reduced risk of endometrial cancer. Symptomatology: The usual presenting symptom of endometrial carcinoma is : 1. postmenopausal bleeding which carries a 10% risk of associated malignancy in the absence of hormone replacement therapy. Curettage,or endometrial sampling is mandatory. 2. Postmenopausal discharge from pyometra carries a 50% risk of associated malignancy. 3. Pain may occur with pyometra or metastatic spread. Diagnosis 1. Hysteroscopy with endometrial curettage 2. endometrial sampling. 3. curettage alone, 4. outpatient endometrial sampling alone,are essential. Curettage is not infallible.on the other hand,if a Pipelle has been correctly introduced and the pathology is benign, or no tissue is obtained,it is most unlikely that malignancy exists. Hysteroscopy,cervical smear(>1%risk of concurrent cervical malignancy) vaginal or abdominal ultrasound for ovarian pathology are advised,when endometrial malignancy is found. For histological classification look at the ppt file. HISTOPATHOLOGY 1. Adenocarcinomas 60 70 %. 2. Adenosquamous Ca 10-20% 3. Papillary Serous Ca 10%. 4. Clear cell Ca 4%. 5. Mucinous Ca 9%. 6. Secretory Ca 1-2%. 7. Squamous cell Ca extremely rare 2
Spread: In general this cancer is slow to spread from the uterine cavity, probably because the endometrium lacks lymphatics. A chest X-ray helps detect lung metastases. Magnetic resonance imaging is preferable to ultrasound for detection of myometrial invasion and pelvic spread. 3
Local Spread: Local Spread Slow invasion of the myometrium is the commonest spread. spread may involve the vaginal vault. It may produce considerable uterine enlargement; 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. Lymphatic Spread: The incidence of this seems to be 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. 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. 4
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 diagnosed at stage. Prognostic factors: 1. Staging diagnosis, 2. extent of myometrial invasion. 3. histological grading(differentiation). are the most important prognostic factors apart from competence of treatment. Stage 5 year survival I 85% II 68% III 42% IV 22% TREATMENT OF ENDOMETRIAL CARCINOMA This is essentialy surgical,with postoperative radiotherapy added when : 1. unfavourable prognostic features are found at surgery, 2. Pre-operative clinical Staging is inaccurate. Progestogen therapy is probably only of value in recurrent disease. Women un fit for op.: Few women are unfit for surgery,and caesium insertion radioactive therapy may be employed for these, but radiation alone is less effective than combined surgical and radiation treatment. Stage I:(treatment) Stage II: Total abdominal hysterectomy and bilateral salpingo-oophorectomy without partial removal of vagina. Peritoneal saline washings are taken for cytology on opening the abdomen and the Abdominal contents carefully examined. Stage IIa carries a similar prognosis to Stage I and may be treated as stage I. Stage IIb,with clinical invasion of the cervix,has a poorer prognosis than Stage I and radical hysterectomy,pelvic lymphadenectomy and para-aortic lymph node sampling are indicated, with a combination of local and external radio therapy as an alternative treatment. 5
Stage III: Following the Staging laparotomy, radical hysterectomy,lymphadenectomy,para-aortic node sampling and removal of as much malignant tissue as possible,omentectorny is carried out. Stage III diseases limited to the pelvis may be treated by radiotherapy. Stage IV: Treatment of this Stage is designed to control tumour growth and alleviate symptoms. Surgery,radiation therapy,cytotoxic therapy and adjuvant progestogen therapy all have a place. Carcinoma of the endometrium compared with ca cervix: The overall results are better than for carcinoma of the cervix,not because it is less malignant tumour,but because treatment is usually given earlier. Post-menopausal bleeding is much more difficult to ignore than the irregular bleeding of the younger woman. RECURRENCE OF ENDOMETRIAL CARCINOMA The incidence of recurrence within 5years is in the region of 30%and is accepted along with the 5- year survival rate as a measure of the effectiveness of the various systems of treatment. The majority recurrences appear within 3 years of treatment. Early recurrence has a poor Prognosis. PROGESTOGENS : Many endometrial carcinomata are hormone dependent and progestogens have been used as part of a combined primary treatment, recurrent or metastatic growths. Between 15%and 50%of recurrences will respond.medroxyprogesterone acetate,400 mg to 600 mg daily Chemotherapy : Chemotherapy Cytotoxic chemotherapy has a limited place in advanced recurrence. Single agent therapy with adriamycin, cisplatinum,cyclophosphamide gives response rates between 20%and 40%. 6