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Rapid response to:

Practice Guidelines

Recognition and initial management of ovarian cancer: summary of NICE guidance

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2073 (Published 21 April 2011) Cite this as: BMJ 2011;342:d2073

Rapid Response:

"Risk Approach" followed by Combination of three modalities (viz. bimanual pelvic examination + ultrasonography + CA-125) of screening would be useful for detection of ovarian cancer

Ovarian cancer the silent killer and the key is early detection. Four
major modes of Ca Ovary screening- screening of risk factors, ultrasound,
CA-125, vaginal/ pelvic examination, are discussed with pros and cons with
practical applicability.

Ovarian cancer is fifth most common cause of cancer deaths worldwide.
In India 5-7 cases per 1, 00,000 women per year are reported that means
25-30 thousand new patients every year. Seeing the 13 billion population
of India, 20% of that are adult women makes it 26 million due for
screening (1). With this enormous burden one must start with screening
with at-risk approach viz those who have following risk factors: age
above 50 years, family history of ovarian, breast and colon cancer,
nulliparity, early menarche and late menopause. Using Fertility drugs,
etc..

Screening the general population is currently neither cost-effective
nor practical. The pelvic examination does not add additional cost for
women who are already undergoing regular gynecologic evaluation and is
reliable when done by an experienced examiner, but it lacks adequate
sensitivity and specificity as a screening test. 1010 postmenopausal women
were recruited for an ovarian cancer screening programme incorporating
serum CA-125 measurement and vaginal examination as initial tests and real
-time ultrasonography as a secondary procedure in selected cases. The
normal range for serum CA-125 in postmenopausal women was established. The
specificity for ovarian cancer of serum CA-125 measurement and vaginal
examination were 97*0% and 97*3%, respectively. The combinations of serum
CA-125 measurement with ultrasound and vaginal examination with ultrasound
achieved specificities of 99*8% and 99*0%, respectively. 100% specificity
was achieved by serum CA-125 measurement with vaginal examination and by
the combination of all three tests. The findings indicate that no
individual screening test has acceptable specificity for ovarian cancer in
postmenopausal women. However, the combination of CA-125 measurement with
ultrasound did achieve acceptable specificity and offers the most hope of
a specific and sensitive method for early detection2.

CA-125: CA 125 is widely distributed on the surface of both healthy
and malignant cells of mesothelial origin, including pleural, pericardial,
peritoneal and endometrial cells, as well as in normal genital tract and
amniotic membrane. Interestingly the molecule is not present on the
surface of normal ovarian cells, but is present in 80% of malignant
ovarian tissue of non mucinous origin (3).

The radioimmunoassay for CA 125, a tumor-specific antigen, is
elevated in 80% of ovarian carcinomas, but only in 50% of women with
cancer limited to the ovary (stage1a & 1b). It may also be elevated in
women with benign ovarian disease and in otherwise healthy women, which
limits its specificity. Osteosarcoma, Adenocarcinoma breast, colon,
uterus, pancreas, lung, vagina, fallopian tube, Meig's syndrome, as well
as benign conditions like acute peritonitis, pelvic inflammatory disease,
pancreatitis, digestive tract, endometriosis, liver disease, heart
failure, normal menstruation and pregnancy etc are some conditions with
elevated Ca-125 (4).

.

Sending all the postmenopausal women for CA-125 and ultrasonogpahy
may not be cost effective measure in resource poor or primary care setups
(5).

Malkasion et al studied 59 patients with histologically proven benign
ovarian cysts. Out of these patients 17 had elevated concentrations of CA
125 (12 > 35 units/ml, 4 > 65 units/ml and 1 > 2000 units/ml). In
another study by Dixia using 153 patients with benign pelvic masses, 10
patients had CA 125 concentrations >188 units/ml and one patient had a
value of more that 400 units/ml. Nolen et al screened 65 biomarkers in
patients with adnexal masses and more than half of the biomarkers differed
significantly between benign and malignant masses (6&7). Ca-125 may be
useful as prognostic marker(8).

Ultrasonography: is more sensitive than pelvic examination in
detecting ovarian abnormalities but lacks specificity in distinguishing
benign from malignant ovarian lesions. Combined with serum CA 125 levels,
ultrasonography may provide an effective screening tool, although cost-
effectiveness has not been demonstrated.

Review of literature from 1990 to 2006 which included 143 studies
showed that Ultrasound findings were similar to CT and MRI in
differentiation of benign from malignant ovarian masses (9).

Clinical Pelvic Examination: Bimanual examination involves insertion
of one or two examiner fingers into the vaginal vault with simultaneous
palpation of the lower abdomen to characterize the size and shape of the
uterus and adnexa; a recto-vaginal examination may also be included.
Following a single elevated CA 125 measurement with abdominal ultrasound
yielded a sensitivity of 58%-79%. Even a test with 99% specificity and
100% sensitivity would yield only 1 in 21 women with a positive screen
actually having the disease (10 &11).

Emphasis is therefore on using powerful tool of clinical pelvic
examination (CPE), which is comparable in detecting ovarian mass early.
Among the abnormal adnexal mass of 19 women with recurrent borderline
tumor, one patient had diagnosis due to persistent free fluid. Gynecologic
examination was suspicious (palpable mass) in 7 cases and obviously
abnormal (large mass or nodules) in another 7. CA 125 serum levels were
elevated in 8 cases (7).

Limitations of the pelvic examination for evaluation of the female
pelvis: Review of the literature indicates that the use of routine pelvic
examination as screening for ovarian malignancy (with or without serum CA-
125 and ultrasound) cannot be justified due to the low prevalence of the
disease. However whenever physician medical and paramedical workers get
chance or in high risk women, can explore pelvis by manual examination and
would prove most economical and effective measure for early detection of
Ca Ovary (12).

Further research is needed by calculating the combined sensitivity
and specificity by putting the above modalities applying tests in series
and parallel: starting from risk approach, bimanual pelvic examination, CA
-125 and ultrasound. This will help to prepare the guidelines for
screening in countries like India where number matters.

Reference:
1.. Madhutandra Sarkar, Hiralal Konar and D. K. Raut. Knowledge and Health
Care-Seeking Behavior in Relation to Gynecological Malignancies in India:
A Study of the Patients with Gynecological Malignancies in a Tertiary Care
Hospital of Kolkata. Obstet Gynecol. 1991 May;77(5):787-92.

2. Ian Jacobs, Jane Bridges, Colin Reynolds. Multimodal Approach To
Screening For Ovarian Cancer. The Lancet, Volume 331, Issue 8580, Pages
268 - 271, 6 February 1988

3. Gerardo Zanetta, Sonia Rota, Andrea Lissoni. Ultrasound, Physical
Examination, and CA 125 Measurement for the Detection of Recurrence after
Conservative Surgery for Early Borderline Ovarian TumorsGynecologic
Oncology. Volume 81, Issue 1, April 2001, Pages 63-66

4. S. Grover, M.A. Quinn, P. Weideman, H. Koh. et al. Screening for
ovarian cancer using serum CA125 and vaginal examination: report on 2550
females. International Journal of Gynecological Cancer. Volume 5, Issue 4,
pages 291-295, July/August 1995

5. Sparks JM, Varner RE. Ovarian cancer screening. Obstet Gynecol.
1991 May;77(5):787-92

6. Danijela Jelovac, MD1; Deborah K. Armstrong Recent Progress in the
Diagnosis and Treatment of Ovarian Cancer CA CANCER J CLIN 2011;61:183-
203

7. Asher V, Hammond R, Duncan TJ. Pelvic mass associated with raised
CA 125 for benign condition: a case report. World J Surg Oncol. 2010 Apr
16;8:28.

8. Ian Jacobs and Robert C. Bast Jr The CA 125 tumour-associated
antigen: a review of the literature Human Reproduction,Volume4, Issue1.Pp.
1-12.

9. Liu J, Xu Y, Wang J. Ultrasonography, computed tomography and
magnetic resonance imaging for diagnosis of ovarian carcinoma. Eur J
Radiol. 2007;62(3):328-34

10. Jacobs IJ, Skates S, Davies AP, Woolas RP, Jeyerajah A, Weidemann
P, Sibley K, Oram DH. Risk of diagnosis of ovarian cancer after raised
serum CA 125 concentration: a prospective cohort study. BMJ.
1996;313(7069):1355-8

11. Guilherme H.C Cantuaria, Roberto Angioli, Leslie Frost.
Comparison of Bimanual Examination With Ultrasound Examination Before
Hysterectomy for Uterine Leiomyoma. Obstetrics & Gynecology
Volume 92, Issue 1, July 1998, Pages 109-112

12. L.A. Padilla, D.M. Radosevich, M.P. Milad et al. Screening
asymptomatic women for ovarian cancer: American College of Preventive
Medicine, Practice Policy Statement. International Journal of Gynecology
& Obstetrics
Volume 88, Issue 1 , Pages 84-88, January 2005

Competing interests: No competing interests

15 May 2011
Neeta Kumar
Scientist C
Neeru Gupta, Pratik Kumar, Kishan k Jani, Jugal Kishore
Indian Council of Medical Research