Published 25 August 2009, doi:10.1136/bmj.b3286
Cite this as: BMJ 2009;339:b3286

Editorials

Diagnosis of ovarian cancer in primary care

Persistent abdominal distension carries the highest predictive value

Worldwide, more than 200 000 new cases of ovarian cancer occur each year, and these account for around 4% of all cancers diagnosed in women.¹ Overall the five year survival rate from ovarian cancer is poor at around 30-40%. For women diagnosed with early stage disease, the five year survival rate is over 70%, but only a fifth of cases are diagnosed early.² For women with late stage disease, the five year survival rate is around 15%. No effective screening test is available.

Earlier identification of symptoms could improve prognosis,^{3 4} and in the linked case control study (doi:10.1136/bmj.b2998), Hamilton and colleagues report the predictive value of symptoms in diagnosing ovarian cancer in primary care.⁵

The late stage of presentation has been blamed on the insidious nature of the disease, which has vague non-specific symptoms. Historically, ovarian cancer has been referred to as the "silent killer" because it was believed that no symptoms were evident in early disease. Deciding which patients to refer to a specialist is difficult for primary care doctors because the presenting symptoms of ovarian cancer are similar to those of abdominal disease and gastrointestinal disease. This, coupled with the fact that primary care doctors on average see only one case of ovarian cancer every five years, means that more than half of women with ovarian cancer are not referred directly to gynaecological cancer clinics, thus delaying diagnosis.⁶ One study found that only 24% of women diagnosed with ovarian cancer were referred urgently.⁷

Over the past decade, several studies have disproved the "silent disease" myth, and research has intensified into using symptoms as a diagnostic tool.⁸ Furthermore, these studies have shown that symptoms are present in more than 90% of woman with early stage disease, and that these symptoms may be present for up to 15 months before diagnosis (AWW Lim. Investigating the potential for expediting diagnosis of ovarian cancer via prompt symptom recognition and "targeted screening" [PhD thesis]. London: Queen Mary University, 2009). Women with ovarian cancer experience symptoms more frequently, severely, and persistently than women without the disease.^{3 6} These symptoms include persistent pelvic and abdominal pain, increased abdominal size or persistent abdominal distension (or both), and difficulty with eating or feeling full quickly.^{6 9} However, the methods used in most studies involve retrospective collection of data directly from women, a long duration between diagnosis and data collection, and the use of checklists. The data are therefore subject to recall, selection, and survivor bias.¹⁰

Although Hamilton and colleagues case-control study uses patients’ medical records and is therefore subject to recording bias, it is large enough to allow the calculation of positive predictive values (PPVs) in primary care for ovarian cancer for all important symptoms, individually and combined. All women aged 40 or more diagnosed with primary ovarian cancer during 2000-7 in 39 general practices in one area of England were included. The participant’s entire primary care record for one year before diagnosis was examined. The study is unique in that it calculated the risk of ovarian cancer across the range of key symptoms and was based in primary care where diagnostic delays are prevalent.

PPVs are measures of the likelihood of a woman with certain symptoms having ovarian cancer. Using multivariable analysis, seven symptoms were associated with ovarian cancer. These were abdominal distension (PPV 2.5%, 95% confidence interval 1.2% to 5.9%), postmenopausal bleeding (0.15%, 0.2% to 0.9%), loss of appetite (0.6%, 0.3% to 1.0%), increased urinary frequency (0.2%, 0.1% to 0.3%), abdominal pain (0.3%, 0.2% to 0.3%), rectal bleeding (0.2%, 0.1% to 0.4%), and abdominal bloating (0.3%, 0.2% to 0.6%). Around 85% of cases and 15% of controls had reported at least one of the seven symptoms to primary care before diagnosis. After excluding symptoms reported in the 180 days before diagnosis, abdominal distension, urinary frequency, and abdominal pain remained independently associated with a diagnosis of ovarian cancer.

Only persistent abdominal distension had a PPV over 1%. The low PPVs reflect the high frequency of abdominal symptoms in the population, together with the relatively low incidence of ovarian cancer. The finding of a PPV of 2.5% for persistent abdominal distension means that it carries the highest risk. It was reported by a third of women with ovarian cancer and, importantly, was equally as common in stages I and II cancer as in advanced disease.

The related term, "bloating," is used by women for both persistent and intermittent abdominal distension. Studies have found that bloating is associated with ovarian cancer, and that it was the most common symptom in women with early stage disease.¹¹ However, the studies did not distinguish between persistent abdominal distension and intermittent bloating. A subsequent study found that 38 of 44 women with ovarian cancer had persistent abdominal distension in contrast to bloating, which was present in only two of these women.⁵ Persistent abdominal distension is not included in the current UK guidance for urgent referral.¹² It is clearly a common and important symptom and warrants urgent referral.

The diagnosis of ovarian cancer will continue to be a challenge for primary care doctors. More research, particularly prospective studies, is needed to improve our knowledge of the predictive value of different symptoms in ovarian cancer. In this respect, the prospective validation of the Goff index,¹³ and a prospective study evaluating symptoms in apparently healthy women participating in the UK ovarian cancer screening trial, are eagerly awaited. What is important for both women and primary care doctors is that ovarian cancer can no longer be regarded as a silent killer.

Cite this as: BMJ 2009;339:b3286

¹ Cancer Research UK Primary Care Education Research Group, Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7DL

Research, doi:10.1136/bmj.b2998

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Competing interests: None declared.

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

References

1. Cancer Research UK. Cancerstats: ovarian cancer. 2004. http://publications.cancerresearchuk.org/epages/crukstore.sf/en_GB/?ViewAction=View&ObjectID=4690&Page=2.
2. Cancer Research UK. UK ovarian cancer statistics. 2009. http://info.cancerresearchuk.org/cancerstats/types/ovary/.
3. Department of Health. Ovarian cancer: key messages for health professionals. 2009. www.dh.gov.uk/en/Healthcare/Cancer/DH_095624.
4. Rufford BD, Jacobs IJ, Menon U. Feasibility of screening for ovarian cancer using symptoms as selection criteria. BJOG 2007;114:59-64.[CrossRef][Web of Science][Medline]
5. Hamilton W, Peters TJ, Bankhead C, Sharp D. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ 2009;339:b2998.[Abstract/Free Full Text]
6. Bankhead CR, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, et al. Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG 2008;115:1008-14.[CrossRef][Web of Science][Medline]
7. Allgar VL, Neal RD, Ali N, Leese B, Heywood P, Proctor G, et al. Urgent GP referrals for suspected lung, colorectal, prostate and ovarian cancer. Br J Gen Pract 2006;56:355-62.[Web of Science][Medline]
8. Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian carcinoma diagnosis: results of a national ovarian cancer survey. Cancer 2000;89:2068-75.[CrossRef][Web of Science][Medline]
9. Goff B, Mandel L, Melancon CH, Muntz HG. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 2004;291:2705-12.[Abstract/Free Full Text]
10. Bankhead C, Kehoe S, Austoker J. Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG 2005;112:857-65.[CrossRef][Web of Science][Medline]
11. Olson SH, Mignone L, Nakraseive C, Caputo TA, Barakat RR, Harlap S. Symptoms of ovarian cancer. Obstet Gynecol 2001;98:212-7.[CrossRef][Web of Science][Medline]
12. National Institute for Health and Clinical Excellence. Referral guidelines for suspected cancer. 2005. www.nice.org.uk/CG27.
13. Goff B, Mandel L, Drescher C, Urban N, Gough S, Schurman K, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer 2007;109:221-7.[CrossRef][Web of Science][Medline]

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