June 1, 2016◆Volume 93, Number 11www.aafp.org/afpAmerican Family Physician 937Ovarian cancer is the most lethal gynecologic cancer. Less than one-half of patients survive for more than five years after diagnosis. Ovarian cancer affects women of all ages but is most commonly diagnosed after menopause. More than 75% of affected women are diagnosed at an advanced stage because early-stage disease is usually asymptomatic and symptoms of late-stage disease are nonspecific. The strongest risk factors are advancing age and family history of ovarian and breast cancer.

1. WHAT IS THE EVIDENCE IN FAVOUR OR
AGAINST OVARIAN CANCER SCREENING?

2. DR. NIRANJAN CHAVAN
MD, FCPS, DGO, MICOG, DICOG, FICOG, DFP,
DIPLOMA IN ENDOSCOPY (USA)
Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H, Sion Hospital
Joint Treasurer Elect, FOGSI (2021-2024)
Member Oncology Committee, SAFOG (2020 onwards)
National Co-Ordinator, FOGSI Medical Disorders in Pregnancy Committee (2019-2021)
Vice President MOGS (2020-2021)
Scientific Secretary, AFG (2020-2021)
Chair & Convener, FOGSI Cell Violence Against Doctors (2015-16)
Dean & Chief Content Director, HIGHGRAD E3 Courses
Chairperson, FOGSI Oncology and TT Committee (2012-2014)
Course Co-Ordinator of 11 batches of MUHS recognized Certificate Course of B.I.M.I.E at L.T.M.G.H
(2010-16)
Member, Oncology Committee AOFOG (2013-2015)
Member, Managing Committee IAGE (2013-17), (2018-20)
Editorial Board, European Journal of Gynaec. Oncology (Italy)
Course Co-Ordinator of 3 batches of Advanced Minimal Access Gynaec Surgery (AMAS) at LTMGH
(2018-19)

3. INTRODUCTION
• Malignant epithelial ovarian tumors account for 90% of all malignancies of the
ovary and are the fourth most common cause of tumor-related death in women.
• The overall lifetime risk of developing ovarian cancer for women in the US is 1.4%
to 1.8%.
• This risk varies from 0.6% for women with no family history, at least three term
pregnancies, and four or more years of oral contraceptive use, to 3.4% for
nulliparous women with no oral contraceptive use.
• For women with a family history, the lifetime risk for ovarian cancer is estimated at
9.4%.

4. NICE GUIDELINES RECOMMEND
• To investigate if a woman (especially if 50 or over) reports having any of the
following symptoms on a persistent or frequent basis – particularly more than 12
times per month: –
1. Persistent abdominal distension.
2. Feeling full (early satiety) and/or loss of appetite.
3. Pelvic or abdominal pain.
4. Increased urinary urgency and/or frequency.

5. • Carry out appropriate tests for ovarian cancer in any woman of 50 or over who
has experienced symptoms within the last 12 months that suggest irritable bowel
syndrome (IBS), because IBS rarely presents for the first time in women of this age.
• Measure Serum CA125 in primary care in women with symptoms that suggest
ovarian cancer. If serum CA125 is 35 IU/ml or greater, ultrasound scan of the
abdomen and pelvis to be done. Any woman with normal serum CA125 (less than
35 IU/ml), or CA125 ≥ 35 IU/ml but a normal ultrasound to be assessed carefully
for other clinical causes of symptoms.

6. EVIDENCE FAVORING SCREENING
• Ovarian cancer screening recommended for women over age of 50.
• Those willing to pursue further work up and investigation if screening is positive.
• Estimated to have a 7 – 9 year benefit from screening.
• Patients with BRCA 1 or BRCA 2 mutations.
• Those with strong family history of ovarian cancers.
• Ovarian cancer screening is not recommended for women with no risk factors.

8. • Studies support the efficacy of risk‐reducing bilateral salpingo‐oophorectomy in
significantly reducing the risk of gynaecological and breast cancer in women who
carry BRCA1 or BRCA2 mutations.
• Women undergoing risk‐reduction bilateral salpingo‐oophorectomy should be
counselled about the effects of early menopause and the available management
options including hormone replacement therapy.

9. • For women with increase risk, after evaluating risks and benefits, ovarian cancer
screening with CA-125 and/or transvaginal ultrasonography can be done.
• In women at inherited risk, usually with mutations in ovarian cancer susceptibility
genes, should receive screening by a combination of transvaginal ultrasonography
and CA-125.
• For patients with mutations in BRCA1 or the mismatch repair genes, MLH1, MSH2,
and MSH6, screening should begin around 30-35 years of age.

10. EVIDENCE AGAINST SCREENING
• Screening is applied in a healthy population to detect those individuals without
symptoms, whereby particular criteria need to be considered such as tumor
prevalence, positive and negative predictive value, safety of respective therapeutic
consequences, and impact on morbidity and mortality.
• Early detection aims at reducing the rate of patients diagnosed in an advanced
stage, focusing on detecting symptomatic patients as early as possible.

12. Regarding screening and early detection, ovarian cancer poses particular
challenges. To date, no screening test has been proven capable of leading to a
mortality benefit.

13. • Tests that have been evaluated for Screening for ovarian cancer short reviewing are
transvaginal ultrasound (TVU), measurement of serum CA-125, a tumor-associated
antigen also known as MUC 16, and the combination of both.
• CA-125 is elevated in over 80% of women with advanced stage but in only up to
50% of women with early stage and its specificity is limited.

14. • Currently, “liquid biopsies” are a hot topic in cancer research. Circulating tumor
cells, cell-free (cf ) desoxyribonucleic acid (DNA), cf micro ribonucleic acid
(microRNAs), or exosomes shed into the blood stream can be seen as surrogate for
the tumor itself and are thus referred to as liquid biopsies.
• Liquid biopsies are derived from serum, plasma, or other body fluids and may
provide noninvasive biomarkers.
• Their potential to improve early diagnosis is theoretically present but transition to
clinic still far.

15. TAKE-HOME MESSAGES
• Currently, no evidence supports benefits of screening for ovarian cancer in the
general population.
• Multimodal methods with serial measurements of CA-125 seem to outperform
single threshold measurements of CA-125 or transvaginal ultrasound alone.
• There are several limitations that still need to be overcome before implementing
liquid biopsies into clinical decision making.