CANCER OF THE OVARY. .pptx

Talks about the epidemiology, risk factors and etiopathogenesis of ovarian cancer, manifestation and clinical management.

1. CANCER OVARY I. BWAGA KIU

2. Introduction Introduction and Epidemiology Pathogenesis Prevention Pathological classification Diagnosis Surgical staging Treatment Survival

3. Ovarian Cancer: Burden of suffering 4 th leading cause of cancer death in women in the U.S. (after lung, breast and colon) Overall 5-year survival rate is 35% The “silent killer”: asymptomatic in early stages 75% diagnosed with advanced stage disease; 5-year survival only 10-28% Woman’s lifetime risk of dying from ovarian cancer is 1.1%

4. Cancer Incidence and Deaths in U.S.Women in 2000 Adapted from Paley,P, Screening for the major malignancies affecting women: Current guidelines. Am J Obstet Gynecol 2001;184: Cancer type # new cases # of deaths Lung 74,600 67,600 Breast 182,800 40,800 Colon 50,400 24,600 Ovarian 23,100 14,000 Endometrial 36,100 6,500 Cervical 12,800 4,600

5. Cancer incidence among women in Uganda

6. Early Detection and Mortality No direct evidence that women with early stage cancer found on screening have lower mortality than women with more advanced disease Indirect evidence supports benefits of early detection: Most important prognostic factor in patients with advanced ovarian cancer is tumor burden after initial debulking Surgical debulking and chemo more effective when cancer detected early

7. The challenge Natural history of ovarian cancer not well understood No well-defined precursor lesion Length of time from localized tumor to dissemination is unknown Multiple efforts underway to develop effective screening method for early detection

8. Theories for development of ovarian cancer Genetic theory accounts for 10% of cases Incessant ovulation theory (Fathalla, 1971); repeated ovulation--- repeated ovarian surface trauma & repair promote carcinogenesis GnRH theory via repeated ovulation Pelvic contamination theory with talc, asbestos, ascending infections (?viral)

9. Proposed Pathogenesis of Ovarian Cancers

10. Risk factors The majority of women with ovarian cancer have no known risk factors Most significant risk factor is genetic predisposition

11. Risk factors: Heredity

12. Additional Risk Factors Age Women over age 50 account for ~80% of all cases (ave. age at dx is 61) Reproductive history early menarche, nulliparity or age >30 at first child-bearing, and late menopause Fertility drugs prolonged use of Clomid, especially without achieving pregnancy Personal history of breast cancer Hormone replacement therapy > 10 years May be associated with 30% increased risk Talcum powder Some studies have shown slightly increased risk in women who use talc powder on genital area American Cancer Society, 2001

13. Protective factors Multiparity: First pregnancy before age 30 Oral contraceptives: 5 years of use cuts risk by nearly half Tubal ligation Hysterectomy Lactation Bilateral oopherectomy

14. PATHOLOGY Primary type 80% Epithelial 80-90% Cystic or solid Non-epithelial Germ cell 10-20% Sex cord stromal 3-5% Unclassified Tumours of unspecialized tissues of the ovary Secondary 20%

15. CELL lines Surface epithelium – specialized mesothelial cells, line cortical inclusions Stromal- spindle cells, give rise to numerous phenotypically diverse cells, hormonally active & produce androstenedione, testosterone & DHEA Germ cells- small, hyperchromatic nuclei & support growing follicle

16. Epithelial tumors

17. GERM CELL TUMOURS (GCT) 2 nd commonest ovarian tomours approx 10-20% Classification Dysgerminoma (Primitive germ cell) Embryonal Ca (tumours of totipotent cells) Tomours of extra embryonic cells Endodermal sinus tomours Choriocarcinoma Tumours of embryonic cells– Teratomas Mature Immature

18. Sex cord stromal tumours (SCST) Granulosa cell tumors Thecomas Fibromas Sertoli-leydig cell tumors Gynandroblastoma (mixed) SCST form abt 5% of ovarian tumours esp after 50 yrs 15-30% produce hormones _ functional

19. Diagnostic tools History Pelvic Exam (including rectal) Transvaginal Ultrasound – detection of masses and mass characteristics Tumor markers – CA-125, LPA (plasma lysophosphatidic acid) CT – assess spread to LN, pelvic and abdominal structures MRI – best for distinguishing malignant from benign tumors

20. Clinically benign vs malignant disease Benign Malignant Unilateral Bilateral Mobile Fixed Feel- cystic Solid/variegated Surface- smooth Irregular Ascites- absent Present Growth- slow Rapid Patient’s age- younger Older Nodular lesion in POD- absent present

21. Diagnosis…investigations

22. DIAGNOSTIC CRITERIA OF OVARIAN TUMOUR ON U/S Benign Malignant Cystic areas with uniformly thin or thick multiple linear echoes Colour Doppler (TVS) evaluation of blood flow: regular vascular branching & flow Cystic areas with irregular heterogenous solid part in more than 50% of tumour volume Neovasculization, low resistance flow with pulsatility index <1.0

23. Diagnostic approach If premenopausal and asymptomatic, with unilateral, mobile, simple cystic mass <8-10cm and no family history, can observe for 4-6 weeks and then repeat TVUS and pelvic exam. If resolved, no further work-up necessary If larger or unchanged, or if character of mass has changed on TVUS, surgical evaluation required

24. Diagnostic Approach If postmenopausal and asymptomatic, with unilateral simple cyst <5cm AND normal CA-125, can follow closely with repeat TVUS All other postmenopausal women with ovarian mass require surgical evaluation

25. Surgical Evaluation Exploratory laparotomy has been the gold standard and includes: Peritoneal washings for cytology Evaluation of frozen section Complete staging procedure if borderline or malignant tumor on frozen section

26. Treatment Depends on staging, tumor type, age, desire for future fertility Can include surgery, chemotherapy and/or radiation therapy Clinical trials are ongoing

27. Surgical treatment Primary debulking and cytoreduction; may include: Bilateral salpingo-oopherectomy Hysterectomy Lymphadenectomy (para-aortic, inguinal) Omentectomy “brushing” of diaphragm, examination of liver

28. Chemotherapy and Radiation Usually 6 cycles of chemotherapy Cisplatin (or Carboplatin) plus Paclitaxel most commonly used combination therapy XRT

29. Screening Strategies Ultrasound (transvaginal vs transabdominal) Color-flow doppler CA-125 Other tumor markers

30. CA-125 Sustained elevation in 82% of women with advanced ovarian cancer, but fewer than 1% of healthy women Poor sensitivity (elevated in only 50% of women with Stage I disease) Poor specificity (elevated in many gynecologic and non-gynecologic malignancies as well as benign conditions)

31. CA-125 also elevated in Malignant conditions Cervical CA Fallopian tube CA Endometrial CA Pancreatic CA Colon CA Breast CA Lymphoma Mesothelioma Benign conditions Endometriosis/Menses Uterine fibroids PID Pregnancy Diverticulitis Pancreatitis Liver disease Renal failure Appendicitis

32. Current Screening Guidelines “Routine screening for ovarian cancer by ultrasound, the measurement of serum tumor markers, or pelvic examination is not recommended. There is insufficient evidence to recommend for or against the screening of asymptomatic women at increased risk of developing ovarian cancer.” U.S.Preventive Services Taskforce , Guidelines from Guide to Clinical Preventive Services, 2 nd edition, 1996

33. Screening Guidelines– cont’d NIH Consensus Conference (1994) women with presumed hereditary cancer syndrome should undergo annual pelvic exams, CA-125 measurements, and TVUS until childbearing is complete or at age 35, at which time prophylactic bilateral oopherectomy is recommended. ACP counsel high risk women about potential harms and benefits of screening

34. MANAGEMENT OF OVARIAN CANCER can we do better?