Gynecologic Cancer: Uterine, Vulvar , and Ovarian

1. Gynecologic Cancer:Uterine, Vulvar, and Ovarian Christopher R. Graber, MD Salina Women’s Clinic 08 March 2011

2. Overview • Endometrial (Uterine) Cancer • Vulvar Cancer • Ovarian Cancer • Typical Presentation and Differential • Risk Factors • Different Types and Staging • Screening • Treatment

3. Endometrial (Uterine) Cancer • A 58 yo obese woman presents with postmenopausal bleeding • 10 years without menses, now has had 4 months with “irregular periods.” No cramping. • A 47 yo long-distance runner presents with heavier menses x 1y • Typical menses: 3-5d, min flow. Now: 5-7d, heavy. • 2.6% of US women, 0.5% lifetime mortality • Typical: 50-65yo; 5% younger than 40

4. Differential - Endometrial Cancer • Perimenopause • Uterine fibroids • Adenomyosis • Uterine or cervical polyp • Postmenopausal endometrial atrophy • Endometrial hyperplasia • Simple and complex • With and without atypia

5. Endometrial CA risk factors • Increased risk • Unopposed estrogen • Menopause >52yo • Obesity (3x<50, 10x>50) • Nulliparity • DM • PCOS • Decreased risk • Ovulation • Progestin therapy • OCPs • Menopause <49yo • Normal weight • Nulliparity

6. Uterine CA – Types • Endometrioid adenocarcinoma • Clear cell carcinoma • Papillary serous carcinoma • Secretory carcinoma • Mucinous carcinoma • Squamous carcinoma

7. Uterine CA – Staging (surgical) • IA – confined, < ½ myometrial invasion • IB – confined, > ½ myometrial invasion • II – cervical stromal invasion • IIIA – invasion of serosa or adnexa • IIIB – vaginal or parametrial involvement • IIIC 1&2 – positive lymph nodes • IVA – invasion of bladder or bowel • IVB – distant metastases

8. Uterine CA – Screening • Always have a high index of suspicion • EMB for any woman >35yo with suspected anovulatory bleeding • EMB for any other woman with long(er) history of anovulatory bleeding and other risk factors • Consider D&C if not able to obtain EMB

9. Uterine CA -- Screening • If postmenopausal and EMB shows atrophy • Consider sono – endometrial stripe that measures less than or equal to 4mm is reassuring • Chances of CA if EMB shows • Simple hyperplasia 1% • Complex hyperplasia 5% • Simple with atypia 10% • Complex with atypia 25%

10. Uterine CA – Treatment • Treatment for CA is surgery • Hysterectomy plus staging procedure • By Gyn Oncology • Hysterectomy alone often done if • Grade I or II • No evidence of spread • Type other than clear cell or papillary serous • Consider progestin therapy for hyperplasia

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12. Overview • Endometrial (Uterine) Cancer • Vulvar Cancer • Ovarian Cancer • Typical Presentation and Differential • Risk Factors • Different Types and Staging • Screening • Treatment

13. Vulvar CA • A 63yo woman with daily itching and occasional bleeding “down there” • Duration: several years • A 45yo woman with history of lichen sclerosus reports she has a sore that won’t heal • 10y history of LS, usually well controlled • 4% of cancer in genital tract • Common age 60-79yo; 15% under 40

14. Vulvar CA – Differential • Hypertrophic vulvar dystrophy • Lichen sclerosus • Benign skin lesions: mole, wart, freckle • Trauma • STI – HSV, syphilis, chancroid • Hidradenitis suppurativa

15. Vulvar CA – Risk Factors • HPV • Vulvar dystrophy • Lichen sclerosus – lifetime risk 3-5% • Cervical or vaginal CA

16. Vulvar CA – Types • Squamous cell carcinoma (90%) • Melanoma • Bartholin’s gland • Basal cell carcinoma • Metastatic

17. Vulvar CA – Staging (surgical) • IA – confined to vulva, ≤ 2cm, ≤1mm invasion • IB – same as IA but >1mm invasion • II – confined to vulva, > 2cm • III – adjacent spread to lower urethra, vagina, anus, and/or unilateral lymph nodes (regional) • IVA – invasion of upper urethra, bladder/rectal mucosa, pelvic bone and/or bilateral LN • IVB – distant metastases including pelvic LN

18. Vulvar CA – Screening • Always have a high index of suspicion • Biopsy any suspicious lesion • Close follow-up for lichen sclerosus • Q 3-6 months • Keyes punch biopsy

19. Vulvar CA – Treatment • Surgical removal • Wide local excision (IA) • Hemivulvectomy • Radical vulvectomy with bilateral inguinal –femoral node dissection

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21. To be continued…

22. Overview • Endometrial (Uterine) Cancer • Vulvar Cancer • Ovarian Cancer • Typical Presentation and Differential • Risk Factors • Different Types and Staging • Screening • Treatment • BRCA overview

23. Ovarian Cancer • 58 yo female complains of abdominal pain for several months; has not seen a doctor for several years • Moderate nausea, weight loss • 18 yo female complains of subacute abdominal pain and urinary frequency; pelvic mass felt on exam • Sono shows 9cm solid and cystic adnexal mass • 5th most common cancer in women in US • Highest fatality-to-case ratio of all GYN CA

24. Ovarian CA – Differential Anything that causes… • Bloating • Pelvic or abdominal pain • Back/leg pain • Diarrhea, gas, nausea, constipation, indigestion • Difficulty eating or feeling full quickly • Pain during sex • Abnormal vaginal bleeding • Trouble breathing

25. Ovarian CA – Risk Factors Increased risk Protective • Age • Infertility • Endometriosis • Nulliparity • Genetics • BRCA, HNPCC • Early menarche/late menopause • ?Milk consumption • ?Vitamin D deficiency • Combined OCPs • 10y  60% reduction • Tubal ligation • Multiparity • Young pregnancy, <25yo

26. Ovarian CA – Types • Epithelial • Serous • Mucinous • Endometrioid • Clear cell • Brenner • Undifferentiated • Germ cell • Dysgerminoma • Yolk sac tumor • Teratoma • Mature and immature • Sex cord-stromal • Granulosa cell • Thecoma/Fibroma • Sertoli-Leydig • Metatstatic

27. Ovarian CA – Staging • Stage I –limited to ovaries • IA – one ovary, confined IB – both ovaries, confined • IC – IA or IB, not confined • Stage II – pelvic extension • IIA – uterus and/or tubes IIB – other pelvic tissues • IIC – IIA or IIB, not confined • Stage III – peritoneal involvement • IIIA – microscopic IIIB – macroscopic, <2cm • IIIC – macroscopic >2cm, positive lymph nodes • Stage IV – distant mets including liver parenchma

28. Ovarian CA – Screening • Routine screening is not recommended • No trial has shown improved M/M with screening • Annual exam • Pelvic ultrasound • CA-125 • Other tumor markers • LDH, AFP, hCG, Estradiol, Testosterone, Alk Phos

29. Ovarian CA – Treatment • Surgery • Removal of affected ovary(s) • Staging procedure: free fluid or washings, peritoneal biopsies, pap smear of diaphragm, infracolic omentectomy, retroperitoneal and paraaortic lymph nodes • Typically also uterus and cervix, overall debulking • Chemotherapy and/or radiation • Paclitaxel, cisplatin, carboplatin • Exceptions: young patient, germ cell tumor, confined to 1 ovary

30. BRCA Overview • BRCA is responsible for approx. 10% of ovarian cancer and 3-5% of breast cancer cases • Tumor suppressor genes that help repair DNA • Defective allele inherited, second copy becomes damaged • “two-hit hypothesis” • BRCA1 on chromosome 17, 1,200 different mutations • BRCA2 on chromosome 13, 1,300 different mutations • Incidence: 1 in 300 to 1 in 800 (1 in 40 Ashkenazi Jews)

31. BRCA Overview • BRCA1 – risk of ovarian cancer is 39-46% • BRCA 2 – risk of ovarian cancer is 12-20% • Baseline risk 1.5% • BRCA1&2 – risk of breast cancer is 65-74% • Baseline risk 12.5% (1 in 8) • Consider referral to a Genetic Counselor

32. BRCA – Who to Test

33. BRCA + – For Ovary • Consider ovarian cancer screening at age 30-35 • Transvaginal sono and CA-125 • Consider prophylacitc bilateral salpingo-oophorectomy at age 40 or after childbearing is done • Reduces ovarian cancer risk by 85-90% • Reduces breast cancer risk by 40-70% if premenopausal • Better results for BRCA2 +

34. BRCA + – For Breast • Consider annual mammo and breast MRI at age 25 • For BRCA 2 – consider tamoxifen • Reduces breast cancer risk by 60% • Consider prohylacitc bilateral mastectomy • Reduces breast cancer risk by 90-95%

35. Breast CA sugery • 1800’s

36. Points to Remember • You won’t find it if you don’t look for it • Postmenopausal bleeding is cancer until proven otherwise • If you’re not sure what it is, biopsy it • Ask about family history of breast/ovarian cancer • No screening for uterine CA • Annual exams are screening for vulvar CA • Always look, at least briefly, before a speculum exam • No screening for ovarian CA • I don’t care what popular magazines say … No, I won’t order a CA-125 just because you want me to.