Published 25 August 2009, doi:10.1136/bmj.b3233
Cite this as: BMJ 2009;339:b3233

Research

Commentary: Diagnosing ovarian cancer—more problems than answers

¹ Health Centre, Bicester OX26 6AT

The primary care based case-control study by Hamilton and colleagues (doi:10.1136/bmj.b2998) identified seven symptoms associated with ovarian cancer: abdominal distension, urinary frequency, abdominal pain, postmenopausal bleeding, loss of appetite, rectal bleeding, and abdominal bloating. The report of the first three of these symptoms at least six months before diagnosis was significantly associated with ovarian cancer. The positive predictive values were below 1%, except for abdominal distension, which had a positive predictive value of 2.5%. This study adds to the evidence base derived from primary care of red flag symptoms for several cancers.¹ This is important as most patients in the United Kingdom present initially to primary rather than secondary care.

These findings are broadly concordant with the recent UK consensus statement on ovarian cancer regarding symptoms that could indicate ovarian cancer.² This proposes that "increased abdominal size/persistent bloating—not bloating that comes and goes"—might indicate ovarian cancer. The study by Hamilton and colleagues, however, also found abdominal bloating to be independently associated with ovarian cancer, though with a positive predictive value of only 0.3%. The difficulty here, as acknowledged by Hamilton and colleagues, is to understand what is meant by "bloating" when it is recorded in the medical record. Is it referring to something that comes and goes (as commonly seen in irritable bowel syndrome) or persistent (increased abdominal girth/abdominal distension)? This is important as referral guidance from the Scottish Intercollegiate Guidelines Network (SIGN)³ and the National Institute for Health and Clinical Excellence (NICE)⁴ currently refer to abdominal bloating but not distension.

Medical records from primary care in the UK are a rich source of data that are used to populate databases—such as the THIN (the health improvement network) and GPRD (the general practice research database)—that have produced several valuable studies. To improve the quality of these data we need to standardise terminology and improve our Read coding in primary care. This has been one of the positive spin-offs of the UK quality and outcomes framework (QOF). This phenomenon was seen in the study of Hamilton and colleagues, whereby the "incidence" of ovarian cancer seemed to increase after the creation of a cancer register became a requirement for the framework.

There is now increasing evidence that ovarian cancer is not a "silent killer" but one that presents with vague symptoms² that have a low positive predictive value for cancer. When a woman presents with such ongoing symptoms and a careful history and abdominal and pelvic examination have not identified a cause, pelvic ultrasonography should be considered. This has a reasonably high sensitivity and specificity for identifying ovarian cancer.⁵ In its key messages for ovarian cancer for health professionals, the Department of Health proposes that women should be tested for CA125 as part of the initial diagnostic investigation,⁶ but this is not supported by current SIGN guidelines³ because of the test’s low sensitivity and specificity.^{5 7} CA125 concentrations have been used as part of the ongoing UK collaborative trial for ovarian cancer screening,⁸ but this involves serial measurements in women without symptoms. In primary care it might be more logical to measure CA125 concentrations in patients with abnormal results on pelvic ultrasonography, pending gynaecological referral.

Cite this as: BMJ 2009;339:b3233

---

Competing interests: None declared.

Provenance and peer review: Commissioned; not externally peer reviewed.

References

1. Jones R, Latinovic R, Charlton J, Gulliford MC. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using general practice research database. BMJ 2007;334:1040-4.[Abstract/Free Full Text]
2. Ovarian cancer UK consensus statement. Eve Appeal and Ovacome, 2008. www.eveappeal.org.uk/media/5381/ovarian%20cancer%20uk%20consensus%20statement.pdf
3. Scottish Intercollegiate Guidelines Network (SIGN). Epithelial ovarian cancer. Edinburgh: SIGN, 2003. (SIGN Publication No 75.) www.sign.ac.uk/guidelines/fulltext/75/section3.html#section312
4. NICE. Referral guidelines for suspected cancer. London: NICE, 2005. www.nice.org.uk/nicemedia/pdf/cg027niceguideline.pdf
5. Troiano RN, Quedens-Case C, Taylor KJ. Correlation of findings on transvaginal sonography with serum CA 125 levels. Am J Roentgenol 1997;168:1587-90.[Abstract/Free Full Text]
6. Department of Health. Ovarian cancer: key messages for health professionals. 2009. www.dh.gov.uk/en/Healthcare/Cancer/DH_095624
7. Moss EL, Hollingworth J, Reynolds TM. The role of CA125 in clinical practice. J Clin Pathol 2005;58:308-12.[Abstract/Free Full Text]
8. Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer and stage distribution of detected cancers: results of the prevalence screen of the UK collaborative trial of ovarian cancer screening (UKCTOCS). Lancet Oncol 2009;10:327-40.[CrossRef][Web of Science][Medline]

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Articles

Risk of ovarian cancer in women with symptoms in primary care: population based case-control study

William Hamilton, Tim J Peters, Clare Bankhead, and Deborah Sharp
BMJ 2009 339: b2998. [Abstract] [Full Text] [PDF]

Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database

Roger Jones, Radoslav Latinovic, Judith Charlton, and Martin C Gulliford
BMJ 2007 334: 1040. [Abstract] [Full Text] [PDF]

Rapid Responses:

Read all Rapid Responses

Atypical presentation of Ovarian cancer

Prakash V Belgaumkar
bmj.com, 28 Aug 2009 [Full text]

Appropritate direction of resources for diagnosis and treatment of ovarian cancer.

S. Michael Crawford
bmj.com, 11 Sep 2009 [Full text]

Online poll

Find out more here>> and here>>