Screening modalities and its effectiveness in ovarian carcinoma

1. SCREENING FOR OVARIAN CANCER

2. Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H, Sion Hospital
Joint Treasurer, FOGSI (2021-2024)
Vice President, MOGS (2021-2022)
Member Oncology Committee, SAFOG (2020-2021) (2021-2023)
Dean AGOG & Chief Content Director, HIGHGRAD & FEMAS Courses
Editor-in-Chief, FEMAS & JGOG Journal
50 publications in International and National Journals with 57 citations
National Coordinator, FOGSI Medical Disorders in Pregnancy Committee
(2019-2021)
Chair & Convener, FOGSI Cell Violence Against Doctors (2015-16)
Member, Oncology Committee AOFOG (2013-2015)
Coordinator of 11 batches of MUHS recognized Certificate Course of B.I.M.I.E at
L.T.M.G.H (2010-16)
Member, Managing Committee IAGE (2013-17), (2018-20)
Editorial Board, European Journal of Gynaec. Oncology (Italy)
Course Coordinator of 3 batches of Advanced Minimal Access Gynaec Surgery
(AMAS) at LTMGH (2018-19)
DR. NIRANJAN CHAVAN
MD, FCPS, DGO, MICOG, DICOG, FICOG, DFP
,
DIPLOMA IN ENDOSCOPY (USA)

3. I know my children will never have to say, ”Mom died of
ovarian cancer”
Angelina Jolie

4. INTRODUCTION
• Ovarian cancer is one of the most common gynecologic cancers that rank third
after cervical and uterine cancer.
• It also has the worst prognosis and the highest mortality rate.
• Although ovarian cancer has a lower prevalence in comparison with breast cancer,
it is three times more lethal, and it is predicted that, by the year 2040, the mortality
rate of this cancer will rise significantly.
Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world:
epidemiology and risk factors. Int J Womens Health. 2019;11:287-299. Published 2019 Apr 30.
doi:10.2147/IJWH.S197604

5. • The high mortality rate of ovarian cancer is
caused by asymptomatic and secret growth of
the tumor, delayed onset of symptoms, and lack
of proper screening that result in its diagnosis in
the advanced stages.
• Thus, silent killer is a name that has been given
to this cancer.
Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology
and risk factors. Int J Womens Health. 2019;11:287-299. Published 2019 Apr 30.
doi:10.2147/IJWH.S197604

7. BGCS GUIDELINES(2019) RECOMMENDATION
• CA125 and pelvic ultrasound scan (+/- TVS as
indicated) should be considered the initial
investigations for post-menopausal women
presenting with signs or symptoms of ovarian cancer.
• Women with an RMI of ≥250 should have further
investigations and be referred to the specialist
gynaecological centre MDT.

8. • There is currently no role for organized screening programmes in women
considered at low risk of development of ovarian cancer .
• The role of ovarian cancer screening in women at high risk of ovarian cancer has yet
to be established.
• Risk-reducing salpingo-oophorectomy (RRSO) prevents development of epithelial
ovarian cancer and reduces mortality in women at high risk for epithelial ovarian
cancer.

9. NICE GUIDELINES(2011) RECOMMENDATION
• 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.

10. • 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.

11. • 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.

12. • 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.

13. SCREENING METHODS
• 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,
• (or the combination of both)
• Liquid Biopsy using patient’s Blood/Plasma

14. 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.

15. EVIDENCE FAVORING 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.

19. METHODOLOGY
• Study published in LANCET 2021, conducted in 13 centers in National Health
Service trusts in England, Wales, and Northern Ireland.
• 3 types of screening were done:
• MMS – Annual Multimodal Screening: CA 125 with Transvaginal Ultrasound
• USS – Annual Transvaginal Screening
• No screening group.

20. 2,02,562 women were included in the analysis:
• 50,625 (25·0%) in the MMS group
• 50,623 (25·0%) in the USS group
• 1,01,314 (50·0%) in the no screening group

21. • At a median follow-up of 16·3 years:
• 2055 women were diagnosed with tubal or ovarian
cancer:
• 522 (1·0%) of 50625 in the MMS group,
• 517 (1·0%) of 50623 in the USS group,
• 1016 (1·0%) of 101314 in the no screening group.
• Compared with no screening group, there was a
47.2% increase in detection of ovarian cancer in
stage I and 24·5% decrease in reaching of cancer to
stage IV disease in the MMS group.

22. RESULT
• The reduction in stage III or IV disease incidence
in the MMS group was not sufficient to translate
into lives saved, illustrating the importance of
specifying cancer mortality as the primary
outcome in screening trials.
• Given that screening did not significantly reduce
ovarian and tubal cancer deaths, general
population screening cannot be recommended.

23. CONCLUSION OF THE STUDY
• 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.

24. RECENT ADVANCES IN OVARIAN
CANCER SCREENING
• LIQUID BIOPSY
• MUC 16 gene

25. LIQUID BIOPSY
• Currently, “liquid biopsies” are a hot topic in
cancer research.
• Circulating tumor cells, cell-free (cf )
desoxyribonucleic acid (DNA), cf micro
ribonucleic acid (microRNAs), Exosomes shed
into the blood stream, can be seen as
surrogate for the tumor itself and are thus
referred to as liquid biopsies.

26. • 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 the
clinic is still far.

28. MUC 16 GENE
• CA125 is a multivalent molecule and
various proteolytic fragments of CA125
are detected in the commercially
available assays.
• More so, its levels might be increased in
other non-malignant conditions.
• We might be able to increase the
sensitivity and specificity of the CA125
assay by grouping and categorizing
patients based on which copy of MUC16
they carry to adjust the quantitative
measurement

29. MUC 16 GENE
• MUC16 is the gene that encodes the
peptide moiety of the CA125 molecule.
• MUC16 domains provide novel
opportunities to develop new assays
and refine current tools to improve the
sensitivity and specificity of CA125 for
population-based screening guidelines.

30. TAKE HOME MESSAGE
• 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.
• We need a screening strategy that can detect ovarian and tubal cancer in
asymptomatic women even earlier in its course and in a larger proportion of
women.

31. REFERENCES
• https://www.nice.org.uk/guidance/qs18/resources/ovarian-cancer-pdf-2098492029637
• https://www.bgcs.org.uk/wp-content/uploads/2019/05/BGCS-Guidelines-Ovarian-Guidelines-2019.pdf
• Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens
Health. 2019;11:287-299. Published 2019 Apr 30. doi:10.2147/IJWH.S197604
• Gohagan JK, Prorok PC, Hayes RB, Kramer BS; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Project Team. The
Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization, and
status. Control Clin Trials. 2000;21(6 Suppl):251S-272S. doi:10.1016/s0197-2456(00)00097-0
• Kobayashi H, Yamada Y, Sado T, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol
Cancer. 2008;18(3):414-420. doi:10.1111/j.1525-1438.2007.01035.x
• Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening
(UKCTOCS): a randomised controlled trial [published correction appears in Lancet. 2016 Mar 5;387(10022):944] [published correction
appears in Lancet. 2016 Mar 5;387(10022):944]. Lancet. 2016;387(10022):945-956. doi:10.1016/S0140-6736(15)01224-6
• McLemore MR, Aouizerat B. Introducing the MUC16 gene: implications for prevention and early detection in epithelial ovarian cancer.
Biol Res Nurs. 2005 Apr;6(4):262-7. doi: 10.1177/1099800404274445. PMID: 15788735.
• Asante DB, Calapre L, Ziman M, Meniawy TM, Gray ES. Liquid biopsy in ovarian cancer using circulating tumor DNA and cells:
Ready for prime time? Cancer Lett. 2020 Jan 1;468:59-71. doi: 10.1016/j.canlet.2019.10.014. Epub 2019 Oct 11. PMID: 31610267.

32. “I haven’t talked much about being a ovarian cancer survivor
because
I don’t really want to define myself that way“
Kathy Bates