Ovarian cancer is classified as a gynaecological cancer, but the symptoms can often be mistaken for a bowel condition (Target Ovarian Cancer, 2022; National Institute for Health and Care Excellence (NICE), 2023a). Target Ovarian Cancer is urging health professionals to recognise the red flags for ovarian cancer in order to prevent a diagnosis from being missed or delayed.
Every year, in the UK, around 7500 women are diagnosed with ovarian cancer and more than 4100 women die from the disease, while the estimated lifetime risk of being diagnosed with ovarian cancer is 1 in 50 (2%) (Cancer Research UK (CRUK), 2021; 2022; 2023). Overall, ovarian cancer is much more common in post-menopausal women aged over 50 years. Most cases of ovarian cancer happen in those who have already gone through the menopause and more than 50 in 100 cases of ovarian cancer are in women over 65 years. However, 1000 women under 50 years old develop ovarian cancer each year (CRUK, 2021).
One in seven women will die within 2 months of their ovarian cancer diagnosis. If diagnosed at the earliest stage, 9 in 10 women will survive (NHS England, 2023). But two-thirds of women are diagnosed late, when the cancer is harder to treat (National Cancer Registration and Analysis Service (NCRAS), 2019).
Unfortunately, nearly half of GPs (44%) mistakenly believe symptoms only present in the later stages of ovarian cancer (Target Ovarian Cancer, 2022), meaning that symptomatic women can be missed, leading to diagnosis in the later stages of the disease. In addition, 32% of women must wait 3 months or more from first visiting their GP to getting a correct diagnosis (Target Ovarian Cancer, 2022). Over a quarter of women with ovarian cancer (27%) are diagnosed through an emergency presentation, for example at the emergency department (NCRAS, 2018).
Why early diagnosis matters
Symptoms of ovarian cancer are non-specific and are often accepted by women as normal changes associated with ageing, such as menopause (Bankhead et al, 2008). This is a dangerous misconception that can lead to late diagnosis and poorer outcomes. That is why it is important that everyone knows the symptoms and health professionals are on the lookout for red flag symptoms that require investigation. Poor awareness of symptoms is further compounded by misconceptions regarding cervical screening – Target Ovarian Cancer's Pathfinder Study found that 40% of women in the general public mistakenly believe that cervical screening detects ovarian cancer (Target Ovarian Cancer, 2022).
The stage of the disease is important to predict the outcome. The proportion of women diagnosed with ovarian cancer who survive for 1 year ranges from 98% with stage 1 and 91% with stage 2, to 74% with stage 3 and only 56% with stage 4 (NHS England, 2023).
It is clear that women who are diagnosed at an early stage have better outcomes. Health professionals working in primary care play a vital role in getting the right diagnosis, as the outcomes for those diagnosed via an emergency presentation are much poorer. Those diagnosed via an emergency presentation, for example presenting to the emergency department, are four times more likely to die within 2 months of diagnosis than those diagnosed via the 2-week wait referral system after a visit to the GP (National Disease Registration Service, 2022). Furthermore, 95% of women diagnosed at the earliest stage survive for at least 5 years compared with just 16% of women diagnosed at the most advanced stage (NHS England, 2023)
Symptoms of ovarian cancer
In 2011, NICE published guidance to carry out tests in primary care if a woman (especially if aged 50 years or over) reports having any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month (NICE, 2023a):
- Persistent abdominal distension (bloating)
- Early satiety and/or loss of appetite
- Pelvic or abdominal pain
- Urinary urgency and/or frequency.
Other symptoms could include:
- Changes in bowel habit (eg, diarrhoea or constipation)
- Extreme fatigue
- Unexplained weight loss.
Symptoms will be:
- Frequent – happening more than 12 times a month
- Persistent
- New – not normal for the patient.
Target Ovarian Cancer has symptom diaries available that can be downloaded or ordered, to aid the woman in analysing the frequency and persistent nature of her symptoms.
Guidance
In 2015, NICE further clarified ‘suspected cancer guidance’ for the primary care team, urging investigations for women who present with the above symptoms (NICE, 2023a; 2023b)
Two of the specific instructions were to:
- Carry out appropriate tests for ovarian cancer in any woman aged 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age
- Carry out tests in primary care if a woman (especially if aged 50 years or over) reports having any increased urinary urgency and/or frequency on a persistent or frequent basis – particularly more than 12 times a month.
Abdominal symptoms
Persisting abdominal pain and/or a change in bowel habit requires tests for bowel cancer. But it must be noted that ovarian cancer also causes these symptoms and should be tested for at the same time. A CA125 blood test should be ordered from the laboratory as part of abdominal investigations (more on this below).
An examination of the abdomen and pelvis at presentation of persisting abdominal symptoms is important. If there is ascites or a pelvic mass, the woman should be referred urgently via the 2-week wait suspected cancer pathway.
However, a ‘normal’ result on examination does not exclude ovarian cancer: the tumour can be small, easily missed and can metastasise without a large mass being present. The most common high-grade serous ovarian cancer grows as small pinprick or microscopic foci, quickly covering the organs of the pelvis and abdomen, which can be difficult to palpate or visualise on ultrasound.
Urinary symptoms
Nurses are well placed to help with earlier diagnosis of ovarian cancer. Practice nurses (PNs) are often involved in the dip-testing of urine samples and processing results of lab tests; nurse practitioners (NPs) are involved with consultations for abdominal symptoms and possible urinary tract infections (UTI). If the woman is recurrently presenting with urinary symptoms, sterile midstream urine samples should raise alarm. The woman may have diabetes, an overactive bladder or interstitial cystitis;however, urgency and frequency are some of the symptoms of ovarian cancer and they need investigation (NICE, 2023a).
In my experience as a GP, it is extremely important to safety net these women. For example, a text message can be sent to the woman after a normal MSU result to prompt her to return, ie, ‘Your urine test is clear, but if you have ongoing symptoms, please book a review.’
The CA125 test
CA125 is a tumour marker that is released from an irritated peritoneal lining and elevated levels will show up in a blood test. It is not specific for ovarian cancer, as it acts as a marker for many other conditions, including benign ones, but is sensitive.
It can be ordered from the laboratory as part of abdominal investigations, along with a full blood count (FBC) for a platelet level and C-reactive protein (CRP). A raised platelet count is an independent marker for malignancy and should always be further investigated (NICE Clinical Knowledge Summaries, 2021). A raised CA125 level is a result above 35 u/ml.
False positives and negatives
The CA125 test unfortunately can produce false-positive and false-negative results.
False positives can occur in other inflammatory conditions such as connective tissue disease, endometriosis, heart failure and other abdominal cancers. Having the blood test during menstruation can also elevate the level and women should be advised to avoid having a test during a period (Kafali et al, 2004).
False-negative results are associated with non-epithelial ovarian cancer subtypes, early stage disease and pre-menopausal status (Target Ovarian Cancer, 2019). Ovarian cancer is an umbrella term for different histological types and they can affect CA125 differently. CA125 is elevated in 80% of patients with advanced disease, but no more than 50% of women with stage 1 disease have elevated CA125 (Sundar et al, 2015).
If a woman has a negative CA125 but continues to have symptoms, a second CA125 should be carried 6 weeks later and if rising, the woman should have further tests (NICE, 2012).
NICE guidance suggests reassessing patients with normal CA125 and ongoing symptoms after 4 weeks. In my practice, I contact follow-up patients after 4 weeks ensuring CA125 is retested no more than 6 weeks later. As a safety netting action, a reminder text can be sent 6 weeks after the initial normal CA125 result, for example: ‘Important reminder, if you are still having bloating, feeling full, pain or urinary frequency, you need a further blood test.’ If you use Accurx or a similar messaging system, this can be set up as a prewritten text and sent via Pathway at the appropriate time.
If the CA125 is abnormal, ie equal to or above 35 u/ml, the woman needs an urgent transvaginal pelvic scan.
However, because of the issue with false positives and negatives, the CA125:
- Cannot be used for screening: If a woman has a family history and wants a test, she should be advised that there is no national advice on this. If she has more than one family member with ovarian or breast cancer, she should have a discussion with a GP about a possible referral for genetic testing.
- Is only a guide: health professionals must remember the possibility of false results. Patients should be counselled when being sent for a test on the potential outcomes and need for further tests.
If you are concerned about a woman with symptoms who has normal tests, you can discuss with colleagues, use ‘advice and guidance’ referral to a gynaecologist and arrange to review the woman again as above.
Case study one
Muriel, 62 years old, presented with diarrhoea. The nurse practitioner (NP) carefully took a history, noting that this was the third time in a month that Muriel had noticed she was looser than normal. As part of the work up, a faecal immunochemical test (FIT) for bowel cancer detection was ordered. This was normal but Muriel was urged to re-contact the practice if her change in habit persisted over the next month. When she confirmed this, she was referred for a sigmoidoscopy and was reassured when this proved to be normal.
Six months later, she saw the NP with indigestion. On careful questioning, it was established that Muriel could not eat her dinner anymore; she was having to stop as she felt too full. Thankfully, the NP was alert and organised a CA125 test. The result of this was elevated at 128 and Muriel was later confirmed to have stage 3 ovarian cancer.
Case study two
Linda, 58 years old, presented to the NP with simple dysuria. It was a Friday afternoon, too late to send a sample to the lab, the dip test was negative, but she had symptoms suggesting a UTI and was given nitrofurantoin.
The following week she was back. The symptoms had not gone away gone and this time, a midstream urine sample was sent to the lab, prior to her leaving with a course of an alternative antibiotic, trimethoprim.
The busy NP subsequently received her result in her usual batch; it showed no growth of organisms and no abnormality under the microscope. It was noted as ‘normal, no action’ and simply filed.
Linda came back 3 weeks later. A different NP saw her, who had had a chance to glance at her recent notes, noting the sterile urine result. She asked Linda if her urine symptoms had gone: ‘No, but I've had a couple of different antibiotics, I think I'm just getting to that age.’ The NP asked if she'd had any other new and persistent symptoms. ‘Well, I seem to have middle aged spread, I can't get my dresses on with my big belly.’
The nurse was alarmed and arranged a CA125 blood test. The level was raised at 84 and Linda was subsequently diagnosed with stage 2 ovarian cancer.
Summary
Ovarian cancer does not present as a typical gynaecological cancer – it can cause bloating, abdominal pain and a change in bowel habit. It is vital that practice nurses, GPs, physician associates – the whole primary care team – recognise that any abdominal symptoms could equal ovarian cancer and that women are appropriately safety netted. Box 1 lists sources of useful information and materials for professionals and patients.
Box 1.Resources and further reading
- Target Ovarian Cancer's guides, posters, leaflets, and other resources, including a symptoms leaflet and a symptoms diary: https://targetovariancancer.org.uk/about-ovarian-cancer/symptoms
- Cancer Research UK's pages dedicated to ovarian cancer, covering symptoms, diagnosis, treatment, and ongoing research: https://www.cancerresearchuk.org/about-cancer/ovarian-cancer
- Target Ovarian Cancer's Pathfinder reports on the state of diagnosis, treatment, and support for ovarian cancer in the UK and early diagnosis in primary care (Target Ovarian Cancer, 2022)
- NICE Clinical Knowledge Summary on ovarian cancer: https://cks.nice.org.uk/topics/ovarian-cancer/
- Target Ovarian Cancer's support line: 020 7923 5475
- Target Ovarian Cancer's training modules and resources for primary care clinicians: https://targetovariancancer.org.uk/health-professionals
- Target Ovarian Cancer's Early Diagnosis Network and GP Network https://targetovariancancer.org.uk/health-professionals/early-diagnosis-network
Remember:
- If you are considering upper and lower gastrointestinal cancers, include a CA125 test
- Never diagnose new-onset IBS in women over 50 years
- Unexplained recurrent urinary symptoms can be a sign of ovarian cancer
- Repeat sterile midstream urine testing should be considered with caution, particularly if the patient is over 50 years
- Beware the false-negative CA125, especially in younger women.
KEY POINTS
- Ovarian cancer is not a rare disease. One in 50 UK females will be diagnosed with ovarian cancer in their lifetime yet our survival rates are some of the poorest in Europe
- Being aware of ovarian cancer's abdominal symptoms of bloating, feeling full up, abdominal pain and urinary frequency can aid early diagnosis and a better outcome
- There is no current screening programme for ovarian cancer and according to research conducted by Target Ovarian Cancer, 40% of women wrongly assume that cervical screening detects it too
- Nurses are ideally placed to both educate women about this devastating disease and facilitate diagnosis
CPD reflective questions
- In which ways could you safety net a woman who presents with symptoms of a urinary tract infection?
- How could you use technology to remind women to be alert to persisting symptoms?
- Why should you be wary of ‘normal results’?
- When women present with ongoing abdominal symptoms, what would you consider as part of your differential diagnoses?
- If a woman presents with a change in bowel habit, what should you be considering in addition to bowel cancer, and what tests should be ordered?