1. Endometrial Cancer ASSOCIATE PROFESSOR Iolanda Blidaru MD, PhD

2. ACS Statistics, 1992 Incidence corpus32,000 ovary21,000 cervix13,500 other4500 Mortality440013,0005600 1000 1000

3. Epidemiology. Physiopathology. Two different pathogenetic types of endometrial cancer 1. Estrogen- dependent tumors u unopposed E exposure, u hyperplasia of the endometrium as initial step, u younger perimenopausal women, u better differentiated, u better prognosis. 2. Estrogen-independent tumors u no unopposed E exposure u no association with hyperplasia of the endometrium; arise on atrophic endometrium u Older, postmenopausal, thin women u less differentiated u poor prognosis.

4. Risk Factors u Age u Hyperestrogenism (ERT, COC, Tamoxifen) u Nulliparity / Infertility u Obesity, Hypothyroidism, Hypertension u Menstrual characteristics (nulliparity, early menarche, late menopause) u Diabetes u Atypical Hyperplasia u Others: smoking, dietary factors

5. Preinvasive Lesions = Endometrial Hyperplasia Endometrial Hyperplasia u Simple Hyperplasia u Complex Hyperplasia u Atypical Hyperplasia: simple / complex (dg. endometrial biopsy, D+C, total hysterectomy) u Treatment: progestins (MPA), hysterectomy, GnRH-a

6. Endometrial carcinoma Histopathology u Endometrioid Adenocarcinoma (80%): G1, G2, G3; ER, PR. u Papillary Serous Adenocarcinoma u Clear Cell Adenocarcinoma u Squamous Cell Carcinoma u Sarcomas ( malignant mixed Mullerian tumors, leiomyosarcoma, endometrial stromal sarcoma )

7. Clinical findings and diagnosis u uterine bleeding in postmenopausal patients (90%) u recurrent intermenstrual bleeding (over 40 years) u atrophic vaginitis u the uterus +/- enlarged, +/- fixed (parametrial, adnexial and/or intraperitoneal spread) u hematometria or pyometria

8. u Any genital bleeding occuring during postmenopause must be investigated to exclude endometrial carcinoma.

9. Investigations u Endometrial biopsy - the diagnostic method endometrial lavage, aspiration cytology, cytology from endocervix and posterior vaginal fornix, hysteroscopy u US, MRI ( uterine invasion, lymph node involvement ) u Estrogen and progesterone receptors u Chest X-ray, computed tomography of the abdomen, urography, u Routine blood counts, urinalysis, sigmoidoscopy, liver function tests, blood urea nitrogen, serum creatinine, glycemia

10. Differential diagnosis u leiomyoma, endometrial hyperplasia with DUB, cervical polyps u cervical, tubal, ovarian carcinoma u atrophic vaginitis u in the premenopausal patient - complications of early pregnancy

11. Staging: Surgical

12. Endometrial CA Staging STAGE I IaLimited to endometrium Ib<1/2 myometrial thickness Ic>1/2 myometrial thickness (Add tumor grade to each stage)

13. Endometrial CA Staging STAGE II IIaCervical glandular involvement IIbCervical stromal involvement (Add tumor grade to each stage)

14. Endometrial CA Staging STAGE III IIIaUterine serosa, positive washings, or adnexal involvement IIIbVaginal metastases IIIcPositive lymph nodes (Add tumor grade to each stage)

15. Endometrial CA Staging STAGE IV IVaBladder or bowel mucosa IVbDistant metastases (Add tumor grade to each stage)

16. Treatment of Endometrial Adenocarcinoma:  Surgery → staging in majority of patients Extrafascial total abdominal hysterectomy / Bilateral salpingo- oophorectomy, peritoneal washings, +/- LND (lymphadenectomy) u RT u Progestins u Chemotherapy

17. Radical Hysterectomy u Removes corpus, cervix, parametria, upper third of vagina u Uterine arteries divided at origin u Ureters dissected through tunnel u Uterosacral ligaments divided near rectum u Typically combined with LND u Oophorectomy mandated

18. Treatment of Endometrial Adenocarcinoma: u Surgery u Radiotherapy -Adjuvant RT for high-risk patients postoperatively -No adjuvant RT if Ia, G1-2 with favorable histology -The only treatment in patients with inoperable stage I and stage II disease u Progestins u Chemotherapy

19. Complications of Radiation Therapy Acute: u Perforation u Fever u Diarrhea u Bladder spasm u Chronic: u Proctitis u Cystitis, UTI u Fistula u Enteritis

20. High-Risk Patients u Deep myometrial invasion u Positive nodes u Grade 3 tumor u Clear cell, papillary serous, squamous or undifferentiated histologies u Positive peritoneal cytology u Other extra-uterine spread

21. Primary Treatment of Uterine Sarcoma u Surgical staging u Single-agent chemotherapy, depending on histology and stage (ADR = adriamycin for leiomyosarcoma, endometrial stromal sarcoma; IFX = ifosfamide for malignant mixed Mullerian tumors) u RT does not appear to alter survival