Ovarian CancerChallenges for Primary Care

Madhavi Venigalla, MDMedical Oncology/Hematology

Lakeland Regional Cancer Center

OBJECTIVES

Discuss screening/early detection practices Describe presenting symptoms Review current recommendations

Ovarian Cancer

Incidence: 1 in 55 womenACS statistics for 2012:22,280 new cases (stable since 1992)15,500 deathsWorldwide: Most common cancer in womenRates highest in developed countries

SymptomsNonspecificPersistent

SymptomsBloatingPelvic or abdominal painDifficulty eating or feeling full quicklyUrgency or urinary frequencyMost common is abdominal enlargement

SymptomsOther symptoms commonly reported

FatigueIndigestionBack painPain with intercourseConstipationMenstrual irregularities

Risk FactorsGenetic predisposition

Family history is strongest riskBreast-ovarian cancer syndromeLynch II syndrome

Cancer of colon, breast, endometrium and HNPCC

Risk Factor (cont’d)Breast-ovarian syndrome

Germline mutation in one of the breast cancer susceptibility genes BRCA or BRCA2

Prevalence General population is 1 in 300 Ashkenazi Jewish is 2 in 100

Risk Factors (cont’d)Age

Annual incidence in women age 50-75 is 50 per 100,000, twice the rate in younger women

Risk Factors (cont’d)Decrease risk:

PregnancyOCPBreast feedingTubal ligationHysterectomy

Increase risk:InfertilityEndometriosisPeri or post

menopausal history of medications

Oral contraceptive UseDuration of use Relative Risk Never 13-6 months .67-11 months .71-4 years .65-9 years .4>9 years .2 N England J Med 316:650 1987

Screening TestsThere is no standardized test to detect

ovarian cancer at an early stageCA-125: most widely used screening method

Specificity is limited False elevations in: endometriosis, fibroids,

cirrhosis w/- ascites, PID, cancers of breast, lung, pancreas, pleural or peritoneal fluid due to any cancer

Clinical TrialsLarge studies in Sweden:

Low positive predictive value of 3%Experts feel a screening protocol should have a

PPV of at least 10% (no more than 9 healthy women with false positive screening would undergo unnecessary procedures for each case of ovarian cancer detected)

Clinical Trials (cont’d)PLCO trial

78,237 healthy women between 55 & 74Annual CA 125 and transvaginal ultrasound4 year follow up: PPV of 2.6%

UK Collaborative Trial of Ovarian Cancer ScreeningPurpose

Evaluate a screening strategy using a risk of ovarian cancer algorithm on the basis of age, CA 125 profile and transvaginal ultrasound

Method (control and screening group)• Primary screening w/CA 125 – if abnormal• Secondary screening w/CA 125 & TVUS

UK Trial (cont’d)• Results:

6532 women were screened and assigned risk levels 1228 intermediate risk had repeat CA 125 and 53

were classified as elevated risk 16 women had surgery

11-benign pathology 1 recurrent breast cancer in ovaries 1 borderline and 3 with invasive epithelial ovarian

cancer Specificity and PPV for primary invasive epithelial

ovarian cancer were 99.8% and 19% respectively JCO Vol 23(31) Nov 1 2005

Novel Tumor MarkerHE4

Human epididymis protein 4Only approved for monitoring women with

ovarian cancer for diagnosing recurrence or progression

Pelvic UltrasonographyObserver dependentUKC TOCS:

48,230 womenPPV was 5.3%

Multimodal Screening

CA 125 and ultrasoundPLCO Usual Care13 year follow-upNo difference in stage of ovarian cancer or

mortality

Synthesis of EvidenceWomen at average risk

Screening is not recommendedWomen at increased risk

Counseling, genetic testingWomen w/high risk family history

NCCN recommends Q6 month CA 125 and TVUS starting @age 30 or 5-10 yrs earlier than earliest age of 1st diagnosis of ovarian cancer

Ovarian Cancer Follow upMonitor CA-125Physical Exam

Including pelvic examCT scan/PET scan as clinically indicatedConsider family history evaluation if not done

previously

Key Points for the NPIdentify at-risk

patientsEducate Intervene earlyProvide evidence

based care