Download OVARIAN CANCER

Practice Easily missed?
Ovarian cancer
BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b4650 (Published 18 November 2009)
Cite this as: BMJ 2009;339:b4650
1. William Hamilton, consultant senior lecturer1,
2. Usha Menon, professor and consultant gynaecologist2
1. 1Academic Unit of Primary Health Care, Department of Community Based Medicine,
University of Bristol, Bristol BS6 2AA
2. 2Academic Gynaecological Oncology, UCL EGA Institute for Women’s Health, Maple
House, London W1T 7DN
1. Correspondence to: U Menon [email protected]
Ovarian cancer is the leading cause of death from gynaecological cancer in the United
Kingdom. Around 4400 deaths occur each year, and UK mortality figures are worse than
comparable European ones.1
Case scenario
Susan was 52 when she first noticed symptoms of urinary urgency, then abdominal swelling
and intermittent abdominal pain. Because at the time she was tearful and tired as a result of
work difficulties, and urinalysis was normal, her general practitioner thought that she was
depressed. After several more attendances, however, her abdomen was examined, and a mass
was felt on vaginal examination. Rapid investigation, including transvaginal ultrasound and
serum CA125, led to surgery and a diagnosis of stage III ovarian cancer.
How common is it?



Just under 7000 new diagnoses are made each year in the United Kingdom
This equates to about one new diagnosis for each full time general practitioner every
five years
About 85% of new cases are diagnosed in women over 50 years
Why is it missed?
The vagueness and non-specific nature of the symptoms, lack of serious pain or physical
disability, and lack of awareness cause women to dismiss the symptoms as being related to
normal body changes, such as the menopause, or to stress.2 The initial symptoms are often
suggestive of benign gastrointestinal or urinary conditions, which are also much more
common than ovarian cancer. The predominance of gastrointestinal symptoms means that
women are often misdiagnosed as having irritable bowel syndrome or gastritis.3 In women
over 50, the new onset of irritable bowel syndrome-like symptoms should raise the possibility
of serious disease, including ovarian cancer.
Even if cancer is considered, colorectal cancer is more common, and patients are often sent
on the wrong investigative pathway. Current UK referral guidelines recommend urgent
investigation only in the presence of abnormal vaginal bleeding or a palpable pelvic mass.4
Both are uncommon early features. Screening is not available—it is still being evaluated in
large randomised controlled trials.
Why does this matter?
Ovarian cancer is staged by the International Federation of Obstetrics and Gynaecology
(FIGO) system. Most women present with advanced stage disease (FIGO III and IV), which
is associated with a five year survival of 25-30% compared with 80-90% in those diagnosed
in early stages (FIGO I or II). The median time to diagnosis is reported as less than three
months in 55% of women, but it was more than six months in 26% and more than a year in
11%.3 Women who ignored their symptoms or presented with gastrointestinal symptoms
were significantly more likely to be diagnosed with advanced disease.3 5
How is it diagnosed?
Clinical diagnosis
Because the incidence of ovarian cancer is relatively low, positive predictive values for most
symptoms are low (table⇓).6 7 Abdominal distension is usually persistent and progressive,
unlike bloating, which most clinicians use to mean intermittent distension. However, women
have their own interpretation of these terms, so it is important to clarify what is meant.8
Main symptoms of ovarian cancer
Symptom
Frequency reported to Positive predictive
GP before diagnosis
value in primary care
Abdominal pain
53%
0.3%
Fatigue
39%
Unknown, but will be
small
Abdominal
distension
36%
2.5%
Diarrhoea
27%
Unknown, but will be
small
Bloating
17%
0.3%
Pelvic pain
16%
Unknown
Increased
urinary
frequency
14%
0.2%
Abnormal vaginal 13%
bleeding
0.5%
Weight loss
Unknown
10%
Main symptoms of ovarian cancer
A symptom index of pelvic or abdominal pain, increased abdominal size or bloating, and
difficulty eating or feeling full, when present for more than a year and occurring on more
than 12 days a month, had a sensitivity of 56.7% for early stage disease and 79.5% for
advanced stage disease. Specificity was 90% for women age over 50 in a US primary care
setting and 86.7% for women under 50 years.9
In the UK, recent guidance urges doctors to look for ovarian cancer in patients with the above
symptoms, especially if they are of recent onset and persistent.10 A similar awareness
campaign is under way in the United States. Abdominal and pelvic examinations are
important—almost half of women may have a palpable mass at diagnosis. If the examination
is negative, women should be encouraged to return if symptoms become more frequent or
pronounced.
Investigations
Serum CA125 and transvaginal ultrasound had a specificity of 95% and 92%, respectively, in
a pilot study of symptomatic women over 45 years in primary care.11 Their sensitivity in
symptomatic women in primary care is unknown, so a negative test cannot completely rule
out cancer. The preferred investigation is a combination of CA125 and pelvic (ideally
transvaginal) ultrasound, which is more sensitive and more specific than either alone in
distinguishing benign from malignant adnexal masses.12 A “risk of malignancy index”—
which combines CA125, menopausal status, and transvaginal ultrasound findings—is often
used to differentiate malignant ovarian masses from benign ones.13
How is it managed?
Surgery is the primary intervention in suspected ovarian cancer, both to obtain histological
confirmation and stage as well as first line treatment. In women who have completed their
families, this usually means laparotomy with removal of the uterus, fallopian tubes, ovaries,
part of the omentum, and any relevant biopsies. If disease is advanced, “debulking” surgery is
performed with the aim of leaving behind as little tumour as possible. Increasing evidence
points to minimal residual disease being associated with better prognosis. Immediately after
surgery, many women are given adjuvant chemotherapy, normally a platinum compound with
paclitaxel added on an individual basis.
Key points




Any of the following three symptoms should raise the possibility of ovarian cancer
especially if they occur on most days, are persistent, or worsening—persistent pelvic
or abdominal pain (or both); increased abdominal size or persistent bloating; and
difficulty eating and feeling full quickly. Other symptoms such as urinary symptoms,
change in bowel habit, extreme fatigue, or back pain may also occur, with or without
those listed above
In women over 50 years, onset of irritable bowel syndrome-like symptoms should
raise the possibility of serious disease, including ovarian cancer
Perform an abdominal and pelvic examination and request serum CA125 and pelvic
ultrasonography if ovarian cancer is suspected, especially in women over 50
When findings are negative, women should be encouraged to return if symptoms
become more frequent or more pronounced
Notes
Cite this as: BMJ 2009;339:b4650
Footnotes





This is a series of occasional articles highlighting conditions that may be commoner
than many doctors realise or may be missed at first presentation. The series advisers
are Anthony Harnden, university lecturer in general practice, Department of Primary
Health Care, University of Oxford, and Richard Lehman, general practitioner,
Banbury. If you would like to suggest a topic for this series please email us
([email protected])
Contributors: WH wrote the first draft, with revision by UM. Both authors are
guarantors.
Competing interests: None declared.
Patient consent not required (patient anonymised, dead, or hypothetical).
Provenance and peer review: Commissioned; externally peer reviewed.
References
1. Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, et al. Recent cancer
survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet
Oncol2007;8:784-96.
2. Fitch M, Deane K, Howell D, Gray R. Women’s experiences with ovarian cancer: reflections
on being diagnosed. Can Oncol Nurs J2002;12:152-68.
3. Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian carcinoma diagnosis.
Cancer2000;89:2068-75.
4. National Institute for Health and Clinical Excellence. Referral guidelines for suspected cancer.
London: NICE, 2005.
5. Ryerson AB, Eheman C, Burton J, McCall N, Blackman D, Subramanian S, et al. Symptoms,
diagnoses, and time to key diagnostic procedures among older US women with ovarian cancer.
Obstet Gynecol2007;109:1053-61.
6. Friedman GD, Skilling JS, Udaltsova NV, Smith LH. Early symptoms of ovarian cancer: a
case-control study without recall bias. Fam Pract2005;22:548-53.
7. Hamilton W, Peters TJ, Bankhead C, Sharp D. Risk of ovarian cancer in women with
symptoms in primary care: population based case-control study. BMJ2009;339:b2998.
8. Bankhead C, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, et al. Identifying
symptoms of ovarian cancer: a qualitative and quantitative study. BJOG2008;115:1008-14.
9. Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of
an ovarian cancer symptom index: possibilities for earlier detection. Cancer2007;109:221-7.
10. Department of Health. Ovarian cancer: key messages for health professionals, 2009.
11. Rufford BD, Jacobs IJ, Menon U. Feasibility of screening for ovarian cancer using symptoms
as selection criteria. BJOG2007;114:59-64.
12. Myers ER, Bastian LA, Havrilesky LJ, Kulasingam SL, Terplan MS, Cline KE, et al.
Management of adnexal mass. Evid Rep Technol Assess2006;130:1-145.
13. Jacobs IJ, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas J. A risk of malignancy index
incorporating CA 125, ultrasound and menopausal status for the accurate preoperative
diagnosis of ovarian cancer. BJOG1990;97:922-9.