Dr W Hamilton, Academic Unit of Primary Health Care, University of Bristol, 25–27 Belgrave Road, Bristol, BS8 2AA, UK. Email email@example.com
Please cite this paper as: Barrett J, Sharp D, Stapley S, Stabb C, Hamilton W. Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care. BJOG 2010;117:610–614.
Objective To identify the routes patients with ovarian cancer take between first symptom presentation and diagnosis.
Design Cohort study.
Setting The study took place in 39 general practices in Devon, UK.
Population All ovarian cancer patients identified in the practices, with a diagnosis between 2000 and 2007 inclusive.
Methods All patients had their cancer symptoms, referrals, and diagnoses identified and dated using their doctors’ records.
Main outcome measures Numbers of patients taking specific routes to diagnosis, together with the time taken to diagnosis.
Results Three main routes to diagnosis emerged. The first was the expected route of outpatient referral: 195 (92% of the total) had at least one of the seven ovarian cancer symptoms or an abdominal mass. A total of 123 (58%) were referred to a specialist, although only 65 (31%) were referred to a gynaecologist. Thirty-five (17%) were initially investigated within primary care by ultrasound scanning, and a further 35 (17%) were admitted as emergencies. The interval from first symptom to referral was similar across the different pathways, with a median (interquartile range) time between the first symptom presenting to primary care and first investigation or referral being 2.5 (0, 27.5) days. The median interval from first symptom reported in primary care to diagnosis was 74.5 (32, 159) days.
Conclusions Only a minority of ovarian cancer patients follow the expected route to diagnosis, of urgent referral to a gynaecologist. In most women, GPs rapidly identified the need to investigate. Avoidable delays generally occurred after the decision to investigate was made.
Around 6800 new ovarian cancers are diagnosed each year in the UK.1 The UK has one of the highest incidences in Europe, together with Nordic countries.2 Mortality is high, with an overall 5-year survival of approximately 35%.3 Survival is very dependent upon stage at diagnosis. In early cancers [International Federation of Obstetrics and Gynecology (FIGO) stage I or II] survival is 80–90%, compared with 25% in late cancers (FIGO III and IV).4 Currently only 30% of patients are diagnosed in the early stages.5 Survival is also worse in the UK, when compared with other European countries.6 Reasons for the UK’s relatively poor performance are being sought in a large international comparison, but almost certainly include delays in diagnosis.7 The countries with the worst ovarian cancer mortality include those with the strongest tradition of primary care, and it is possible that the ‘gatekeeping’ role of primary care (whereby access to specialist care is only available through a primary care referral) may contribute to diagnostic delays. Other reasons for diagnostic delays are possible, especially limited access to investigations.
No validated screening test is currently available, although trials of screening are ongoing.8,9 Thus, most cancers present initially to primary care, and the main prospect for earlier diagnosis is the improved identification of symptomatic cancer.10,11 Until recently, ovarian cancer was considered to have few symptoms. However, several recent studies have shown that symptoms are frequent, although they often go unrecognised by women and doctors, because of their non-specific nature.12–14 Abdominal pain, abdominal distension, pelvic pain, increased urinary frequency, constipation or diarrhoea, abnormal vaginal bleeding, weight loss, abdominal bloating and fatigue have all been reported.8,13,15 However, these symptoms are also common in non-malignant conditions; indeed, 95% of women attending primary care have a symptom potentially representing ovarian cancer.11
If ovarian cancer is suspected, two investigations are available in primary care: CA125 antigen and ultrasound scanning. CA125 levels were raised at diagnosis in all but 7.6% of women with FIGO III and IV cancers in a secondary care study.16 However, in asymptomatic women invited for screening, only 0.6–0.9% have a persistently raised CA125 level.9,17 The performance characteristics of CA125 in the symptomatic primary care population (as opposed to the asymptomatic screening population) has not been reported. There is concern about the number of false positives that could arise from the increased use of CA125, which may be raised in many conditions.18 Although abdominal ultrasound is widely available in primary care, transvaginal ultrasound (the preferred imaging modality) is not usually directly available to GPs. Thus, GPs refer patients suspected to have ovarian cancer to a gynaecologist. Current UK guidance for referral of suspected cancer recommends urgent investigation only for abnormal vaginal bleeding and palpable masses.19 The combination of a relatively rare cancer, which produces symptoms of a low predictive value, allied to patchy investigative services may well be contributing to diagnostic delays, which may in turn have worsened the prognosis. Ovarian cancer has recently been selected as one of the three cancers (together with colorectal and lung) for increased primary care access to investigations, with implementation planned to begin in 2011.
Much investment in cancer diagnostic services involved providing rapid investigation services within the ‘2-week clinics’. However, this assumes that patients are identified in primary care as being at risk and referred to such clinics. We sought to test this hypothesis by mapping out the pathways patients take from first symptom of ovarian cancer presenting in primary care to diagnosis.
This study was nested within a retrospective case-control study aimed at identifying and quantifying clinical features of ovarian cancer.13 All 212 primary ovarian cancer cases in women aged ≥40 years, diagnosed during 2000–2007 inclusive, living in Exeter, Mid-Devon or East-Devon, England, were identified from 39 participating general practices in these areas. Anonymised copies of the GP’s records, referral letters, specialist consultations and imaging results were taken. Seven symptoms were found to be independently associated with ovarian cancer in the year before diagnosis: abdominal distension, post-menopausal bleeding, loss of appetite, increased urinary frequency, abdominal pain, rectal bleeding, and abdominal bloating.
In this cohort study, the pathway from the first consultation in primary care with a feature of possible ovarian cancer to diagnosis was identified. The date of diagnosis was taken as the date that histological proof was obtained, or in the few that were diagnosed without histology, the date that a gynaecologist made the diagnosis. As the intervals between first symptom and diagnosis were not normally distributed, medians and interquartile ranges were used for analysis, with median tests for significance testing.
The 212 patients with ovarian cancer had a median age of 67 years (interquartile range 58.5–77.5). The several possible pathways towards diagnosis are shown in Figure 1.
Seventeen patients (8% of the total) had no features of ovarian cancer recorded in their notes in the year before diagnosis: 13 reported symptoms of their cancer to a non-gynaecological specialist, and were referred to a gynaecologist by that specialist; the remaining four (2%) presented acutely unwell to general practice without specific symptoms of ovarian cancer, and were admitted as an emergency, although ovarian cancer was not suspected. The remaining 195 (92% of the total) had at least one of the seven ovarian cancer symptoms described earlier or an abdominal mass. Of these, 123 (58%) were referred to a specialist, although only 65 (31%) were referred to a gynaecologist. Thirty-five (17%) women with a symptom of ovarian cancer were admitted to hospital acutely unwell without any prior referral for investigation. Thirty-five (17%) women had an ultrasound requested by their GP. The intervals between first symptom, first investigative action (either referral or request of an ultrasound) and diagnosis are shown in Table 1. The difference in intervals from first symptom to diagnosis (which we call the diagnostic interval from now on) across the three non-emergency categories—gynaecology, other specialities and ultrasound—was of borderline significance (P = 0.091, median test 2 df).
Table 1. Intervals between symptom presentation, referral and diagnosis for ovarian cancer patients presenting a symptom to primary care
Time in days between the two events (median, IQR)
First symptom presented in primary care to referral
Referral to diagnosis
Two women who had reported symptoms of their cancer to their GP had no investigative action initiated by the GP, with their cancer being discovered by secondary care. Their intervals from first symptom in primary care to diagnosis were 167 and 327 days.
Gynaecology (n = 65)
0 (0, 22)
50 (29.5, 88.5)
79 (44, 152)
Other (n = 57)
3 (0, 33)
64 (27, 117)
97 (37, 232)
Emergency (n = 35)
9 (0, 50)
11 (3, 23)
40 (13, 157)
Radiology (n = 35)
2 (0, 15)
53 (29, 77)
57 (38, 108)
Total (n = 193)
2.5 (0, 27.5)
48.5 (17, 89)
74.5 (32, 159)
Forty-four women had a CA125 result in their records, all abnormal: it was not possible to identify whether these had been requested in primary or secondary care. One of these was a week after a woman had been admitted to hospital as an emergency; 13 were in women referred for ultrasound, with three of these ocurring more than 30 days after the ultrasound was requested; ten were in women referred to non-gynaecological specialities, of which all ten ocurred more than 30 days after the referral. Finally, 20 of the abnormal CA125 results were in women referred to a gynaecologist, only four of which ocurred 30 days after the referral. It is likely that all of the CA125 tests were taken more than 30 days after the other investigative actions were taken in secondary care.
This is the first study to map out the routes to diagnosis taken by women with ovarian cancer. There were three main routes. The majority (58%) were referred by their GP for specialist investigation as outpatients, although almost half of these were to departments other than gynaecology. A further 19% presented as an emergency, although it was not always clear from the records that the primary reason for admission was a suspected ovarian cancer. A smaller group (17%) were initially investigated in primary care with ultrasound, and were referred after an abnormal result was found. Finally, the smallest group was the 6% of women whose diagnosis was made without any apparent primary care input at all. Overall, this means that only 48% of the cohort took the standard pathway of either a gynaecological referral or primary care investigation, followed by referral to gynaecology. Differences in the diagnostic interval were relatively small, and only of borderline significance. GPs identified the need for investigation rapidly in most women, who were referred quickly, although a small but important proportion of women experienced delays in referral.
Strengths and weaknesses
This is a single cohort from one county in the UK, and may not be typical. It is relatively small. It overlaps with the introduction of the first referral guidance for suspected cancer sent to GPs in 2000, and updated in 2005.19 Furthermore, the data originate from the GP records, and any omissions in medical recording of symptoms, investigations or referrals will have weakened this study. We also used only the symptoms that were found to be independently associated with ovarian cancer in the main study.13 Although this was a consistent approach, other symptoms have been reported by women—such as fatigue—and these were not studied here.
Comparison with previous literature
No primary care study has identified what proportions of ovarian cancer patients take the different routes to diagnosis. This is especially relevant currently, with recent UK and Danish initiatives to increase the availability of imaging in primary care. Much recent work has concentrated on outpatient referrals, and whether patients take the urgent or non-urgent route. In a large UK study of cancers in 1999 and 2000, Allgar reported that 87% of ovarian cancer patients had seen their GP before diagnosis, a slightly lower percentage than reported here.20 These were self-reports rather than data from GP records, perhaps explaining some of the difference. A recent UK electronic database study also reported that 87% of women had described symptoms of their cancer to a GP, and estimated a median diagnostic interval of 19.5 weeks.14 Taken together, these studies suggest that symptoms are common, and in most women are acted upon swiftly by GPs. As with most cancers, a minority of women experience longer delays, which may contribute to a poor outcome.
Implications of the findings
The main finding is that only a minority of patients take the standard route of GP referral to a gynaecologist. In part this reflects the women admitted as emergencies (roughly the same proportion of patients with colorectal cancer or lung cancers are first diagnosed during an emergency admission).21,22 The other likely explanation is that the symptoms of ovarian cancer are non-specific, and are often not easy to attribute to a gynaecological source. This probably explains those patients who were referred to other specialties. However, most women received rapid recognition that they were ill, and most of the diagnostic interval occurred after investigations were initiated. This argues that diagnostic delays in primary care are more a result of suboptimal access to investigation than a result of GPs failing to recognise the need to investigate. In this respect, the recent improvements in the UK’s National Health Service (NHS) provision of imaging are very welcome.
Finally, policymakers need to address how to encourage women to attend their GP when they have a symptom of ovarian cancer. Early presentation may obviate some of the emergency admissions. Awareness of ovarian cancer symptoms in the general public is extremely low.23 Several campaigns by the UK ovarian cancer charities are trying to raise symptom awareness. There is a fine balancing act between promoting early presentation and a need to avoid overwhelming GPs and radiology departments.13 In this respect, access to imaging has been viewed as a priority, and waiting times for this have fallen recently—this can only be helpful.
Disclosure of interests
WH has spoken at some charity functions run by ovarian cancer charities, one aim of which is to raise the awareness of ovarian cancer symptoms. He is on the steering group of the Pathfinder Study, run by Target Ovarian Cancer. He is not remunerated for any of these activities, but receives his travel expenses.
Contribution to authorship
WH and JB were involved in all areas. SS and CS collected data, and helped with the analysis and writing of the paper. DS helped with the design of the study, the interpretation of the results, and the writing of the manuscript.
Details of ethics approval
The study was approved by the North and East Devon research ethics committee.
This work was undertaken by the authors, who received funding from the Department of Health’s National Institute for Health Research (NIHR) School for Primary Care Research. The views expressed in this publication are those of the authors, and not necessarily those of the Department of Health. Additionally, WH is funded through an NCCRCD post-doctoral fellowship, and his research practice in Exeter received funding from the Department of Health’s Research Practices scheme. The study sponsor was the University of Bristol. The authors were independent from the funder and sponsor, who had no role in the conduct, analysis or the decision to publish.
We wish to thank all 39 participating general practices in Devon for their enthusiasm.