Ovarian Cancer Screening

Dr Stuart Salfinger Gynaecologic Oncologist WA Gynaecologic Cancer Service KEMH & SJOG Hospitals

NO

DON’T DO IT!

NBOCC, RANZCOG, ASGO Statement Population screening and early detection of

ovarian cancer in asymptomatic women

There is currently no evidence that any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including

transvaginal ultrasound), or combination of tests, results in reduced mortality from ovarian cancer.

There is no evidence to support the use of any test, including pelvic examination, CA125, or other biomarkers, ultrasound

(including transvaginal ultrasound), or combination of tests, for routine population based screening for ovarian cancer.

Further validation in large clinical trials is required before current or new biomarkers could be recommended for routine use in a

population screening setting.

Ovarian Carcinoma

High Mortality Leading cause of death from gynaecologic malignancy Relatively uncommon (incidence 10/100,000) 2009 - 1300 diagnosed, 800 died Usually advanced disease Stage 3 – 5yr survival 30%

Screening Principles

Requires strong evidence base Benefit > harm Disease criteria important problem latent or early asymptomatic Test criteria sensitivity, specificity validation safety high PPV NPV

Limitations - Ovarian cancer and screening

No premalignant or precursor lesion Current screening tests can not detect ovarian carcinoma early enough to alter the natural history of disease Low prevalence affects sensitivity and specificity Example 100,000 tested, prevalence 0.05% Even with sensitivity 99.9% Specificity 97.5% Results in 50 True positives and 2500 False positives (PPV 1.96%) Because of the high mortality need high sens. and spec. to intervene

Current Tests

Ca 125 HMW Glycoprotein Poor Sensitivity and specificity in early disease 50% stage 1 elevated levels 90% stage 3 elevated levels Specificity limited as elevated in many benign conditions

Current Tests

TV USS Morphology and volume to detect changes Vascularity, Doppler Specificity low High FP rate – unnecessary surgery Weighted morphology scoring systems No consensus yet

Current Tests

Combined TV USS and Ca 125 Reduces false positives Repeat Ca 125 over time even better ROC algorithm UK Collaborative Trial Ovarian Cancer Screening

Current Tests Biomarkers

Improved Spec. and Sens. Gene microarray profiling Proteomic technology “Panels” of biomarkers Spec 99% and Sens 91% (early stage) No prospective trials in healthy asymptomatic populations No evidence for survival advantage using these markers in screening context

Current Tests Ovplex Commercially available test Ca125 & 4 other biomarkers Unpublished data – Sens 94% Spec 91% All stages, phase 2 study, 150 cancers, 212 controls

Current Tests

HE-4 Biomarker Combined with ca125 – Improved sensitivity and specificity compared with ca125 alone Promising triage tool for women with masses No data to support use as screening tool

Trials

PLCO (Prostate, Lung, Colorectal, Ovarian) Prospective RCT 70,000 women, Ca125 & USS PPV combined 23.5% Finished after 2010 UKCTOCS (UK Collaborative Trial Ovarian Cancer Screening) Prospective RCT 200,000 women, 3 arms, control, TVUSS, Ca1256 and USS in algorithm Screening till 2011, results 2014

Risk Factors

RR Lifetime Genetic Predisposition Familial Cancer Syndrome ? 30-50% 2-3 relatives ovarian carcinoma 4.6 5.5% (15) 1 relative ovarian carcinoma 3.1 3.7% (5) Nil 1.0 1.8% OCP Use 0.65 0.8% Pregnancy 0.5 0.6% Infertility 2.8 Nulliparity 1.6 Breast feeding 0.81 Tubal Ligation 0.59

Cost Effectiveness

Estimates range 100,000 – 250,000 (USD) per life year saved Generally screening must be <150,000 Need to consider the cost of interventions unnecessary surgery complications of surgery Await long term data from large RCT’s

High Risk Women 1261 Women FHx, 6082 screens (Karlan et al, Am J O&G, 1999) 3 early stage cancers detected 7 cases advanced disease missed 383 Women HBOC gene (Meeuwissen et al, Gyn Onc, 2005) 20 exploratory surgeries (abnormal screen) 1 malignancy found – (metastatic breast!) 2 interval cancers missed despite screening 312 BRCA Women (Olivier et al, Gyn Onc, 2006) Sens 40%, Spec 99% 4 early stage cancers (3 at prophylactic surgery with normal screen) 888 BRCA women (Hermsen et al, Br J Cancer, 2007) 10 incident cancers, 5 had normal screen, 80% stage 3 28460 Women high risk history PLCO (Lacey et al, Obst Gyn, 2006) PPV 2.8% in highest risk group

HBOC Syndrome Women ACOG recommend PERIODIC(?) screening with CA 125 and TVUS beginning between the ages of 30 and 35 years NCCN recommend six monthly screening with CA 125 and TVUS beginning between the ages of 30 and 35 years National Cancer Institute- there is not sufficient evidence to support screening for ovarian cancer in any population, including women at increased risk.

HBOC Syndrome Women

The evidence indicates limited effectiveness of screening in this population, and clinicians and patients should not be falsely reassured by negative screening test results. Consideration of OCP use The ONLY proven intervention to decrease the risk of ovarian carcinoma in this population is prophylactic surgery

Asymptomatic women

THERE IS NO ROLE FOR SCREENING US Preventive Services Task Force National Comprehensive Cancer Network American College of Obstetricians and Gynecologists Canadian Task Force on the Periodic Health Examination The National Cancer Institute Royal Australian New Zealand College Obstetrics & Gynaecology National Breast and Ovarian Cancer Centre Australian Society Gynaecologic Oncologists