Diagnosing ovarian cancer
Diagnosing and treating ovarian cancer has historically proven to be a major challenge for healthcare professionals involved at all points in the patient care pathway, but perhaps none more so than for the general practitioner. This is largely due to the perception that ovarian cancer only presents with symptoms when disease is very advanced.
In this section we will present some of the most recent and compelling symptoms research emerging from the U.K and the U.S. There is also information on latest facts and figures, and the major risk factors associated with ovarian cancer, challenges faced by the general practitioner in diagnosing ovarian cancer and some suggestions for improving diagnosis in general practice.
Ovarian cancer is the fourth most common cause of death from cancer in women after lung, breast and bowel cancer, claiming approximately 4400 lives each year.
- The current UK 5-year survival rate is 36% as most women have metastatic disease at the point of diagnosis. This is in contrast to the U.S. 5-year survival rate which is almost 50%
- Survival rates can be as high as 70% in patients where tumours are confined to the ovary at diagnosis
The two greatest risk factors for developing ovarian cancer are, age, and family history. Risk increases sharply in post-menopausal women with almost 85% of all diagnosed cases occurring in women over the age of 50. A number of other factors including environmental, reproductive and lifestyle factors have all been shown to influence a womans risk of developing ovarian cancer. However, the impact of these risk factors is relatively small when compared with age and family history.
There is currently no national screening programme for ovarian cancer in the UK. Two clinical trials are underway to assess the impact of screening on ovarian cancer mortality. Both trials are using the Transvaginal Ultrasound (TVU) and CA125 serum assay as diagnostic tests.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening study has recruited 200,000 women between the ages 50-74 from centres across the UK. Results from this study are expected to be published in the next 5 years.
Participants in the trial are assigned to 1 of 3 groups:
- Group 1: Women are given an annual CA125 test, a positive test is followed by a TVU
- Group 2: Women are given an annual TVU, abnormal scans are followed by a CA125 test
- Group 3: Control group
The United Kingdom Familial Ovarian Cancer Screening Study will assess if regular screening is beneficial for women at high-risk of developing ovarian cancer. The trial recruited 5000 women aged 35 or over. Recruitment closed in December 2009.
Women participating in the trial will have:
- CA125 test 3 times a year for up to 4 years
- TVU once a year for up to 4 years. This may be more regular if the CA125 test result is abnormal
This is expected to report in the next 5 years.
Recent research has provided conclusive evidence that a distinct set of symptoms are experienced, even by patients with very early disease. Importantly symptoms are not usually gynaecological in nature, but are often indicative of conditions affecting the abdomen or gastrointestinal tract.
- Persistent abdominal distension (‘bloating’)
- Feeling full (early satiety) and/or loss of appetite
- Pelvic or abdominal pain
- Increased urinary urgency and/or frequency
Occasionally there are other symptoms:
- Changes in bowel habit
- Extreme fatigue
- Unexplained weight loss
Critically it is not just the presence of symptoms that helps to indicate ovarian cancer.
It is recognised that women who are diagnosed with ovarian cancer tend to experience symptoms that are more persistent and frequent than similar symptoms caused by other conditions, for example, irritable bowel syndrome. Symptoms usually occur more than 12 times per month.
In Spring 2011 the National Institute for Health and Clinical Excellence (NICE) published a new clinical guideline ‘Ovarian Cancer: the recognition and initial management of ovarian cancer’ this guideline gives for the very first time, healthcare professionals in primary care in England and Wales, clear guidance on how to manage symptomatic women.
The guideline recommends the following:
- If physical examination identifies ascites and/or a pelvic or abdominal mass, the woman should be referred urgently.
- Women reporting persistent or frequent symptoms, highly indicative of ovarian cancer should be given a serum CA125 test, particularly if they are aged 50 or over.
- If the CA125 is greater than 35 IU/ml then an ultrasound of the abdomen and pelvis should be arranged.
- If the ultrasound suggests ovarian cancer then the woman should be referred to gynaeoncology.
- Advise women with a normal CA125, or a CA125 greater than 35 IU/ml but a normal ultrasound to return for re-assessment if symptoms persist.
A common clinical scenario not covered in the recommendations made in the NICE clinical guideline is how to manage patients who present with symptoms but have either normal CA125, or raised CA125 but normal ultrasound. Publication of the NICE Quality Standard for ovarian cancer (2012) and the Department of Health document Direct Access to Diagnostic Tests for Cancer (2012) both provide additional information which will help general practitioners manage women appropriately.
A CA125 result in below the 35 IU/ml threshold does not exclude ovarian cancer in symptomatic women.
- The NICE quality standard for ovarian cancer states that ‘women with normal CA125 or, or raised CA125 but normal ultrasound, with no confirmed diagnosis but continuing symptoms, are reassessed by their GP within 1 month.
- The Department of Health state that if CA125 is below 35 IU/ml then organise a review of patient at 6 weeks. Ensure appropriate safety netting for re-attendance if symptomatic. If there are still concerns regarding the possibility of ovarian cancer arrange an ultrasound, ideally within 4 weeks.
A primary care based, case-control study by Dr Willie Hamilton academic GP at the University of Bristol, (and advisory panel member for the Target Ovarian Cancer Pathfinder Study) identified symptoms associated with ovarian cancer. Abdominal distension (increased abdominal size/persistent bloating – not bloating that comes and goes) was found to have a positive predictive value of 2.5% compared with 1% for other symptoms, and was also found to be independently associated with ovarian cancer. Dr Hamilton concludes that abdominal distention is a high-risk symptoms warranting rapid investigation.
Common problems diagnosing ovarian cancer: possible solutions
Three out of every four women diagnosed with ovarian cancer will have late stage disease at the point of diagnosis; and 30-40% of women with ovarian cancer will experience symptoms for 6 months or more before diagnosis. The challenge for the general practitioner is in the detective work required to weed out cases of ovarian cancer from cases of non-malignant disease.
It is common for patients presenting with symptoms of ovarian cancer to initially receive a diagnosis of:
- Irritable bowel syndrome (IBS)
- Acid reflux
- Urinary tract infection, and
- Changing menopausal status
NICE clinical guideline Ovarian Cancer: the recognition and initial management of ovarian cancer advises that women over 50 rarely present with IBS for the first time, but 85% of ovarian cancer cases are diagnosed in women aged 50 or over.
British researcher Dr Clare Bankhead and colleagues at the University of Oxford department for primary health care have also contributed to the new generation of symptom research. They conclude that one of the key challenges which can often hamper the diagnosis of ovarian cancer in general practice is the difference in descriptive language used by patients and doctors.
Women often use the term ‘bloating’ to describe the symptoms they are experiencing. However the study by Bankhead et al recognised that ‘bloating’ may represent 2 distinct symptoms:
- Abdominal distention, and
- Fluctuating bloating and discomfort
Since persistent distension is a key indicator of ovarian cancer and fluctuating bloating is not, a major challenge general practitioners face is teasing from patients the exact nature of their symptoms.
Follow up consultation
Very often the symptoms associated with ovarian can be attributed to non-malignant conditions and an approach to rule common conditions in or out is adopted. Women often fail to return for a follow up consultation even if their symptoms are not alleviated by the medication or lifestyle changes recommended in the initial consultation.
Encouraging women to:
- Book a follow-up consultation if symptoms persist (especially in cases where ovarian cancer is suspected) and,
- Suggest patients keep a record of symptom frequency and persistency
may facilitate diagnosis.
Patient follow up
Since it is widely acknowledged that they symptoms of ovarian cancer can be attributed to a number of other common medical conditions, the difficulty for GP's is knowing which women they should be concerned about.
In cases where there is:
Little or no reason to suspect ovarian cancer - reassure the patient, explaining why the symptoms are not indicative of ovarian cancer. Recommend that if symptoms persist or get worse the patient should make another appointment, and suggest keeping a diary of symptoms
Some suspicion of ovarian cancer -
If physical examination identifies ascites and/or a pelvic or abdominal mass, the woman should be referred urgently.
Women reporting persistent or frequent symptoms, highly indicative of ovarian cancer should be given a serum CA125 test, particularly if they are aged 50 or over.
If the CA125 is greater than 35 IU/ml then an ultrasound of the abdomen and pelvis should be arranged.
Advise women with a normal CA125, or a CA125 greater than 35 IU/ml but a normal ultrasound to return for re-assessment if symptoms persist.
High index of suspicion -
If the CA125 and ultrasound suggests ovarian cancer then the woman should be referred to gynaeoncology.
The patient should be referred according to guidelines published by your local Trust and/or per the 2 Week Wait suspected cancer referrals as per NICE guidelines.
If ovarian cancer is diagnosed, surgery should be performed by a Gynaecological Oncologist