Mr Charles Redman explains how the NICE guideline highlights the role of primary care in ensuring that women with suspected ovarian cancer are referred promptly

Ovarian cancer is the fifth most common cancer in women, with approximately 6700 new cases diagnosed every year in the UK.1,2 Nearly 60% of women will not live beyond 5 years of diagnosis.3

While there are effective treatments available, the stage of ovarian cancer at diagnosis is the most important factor in predicting survival. Currently, most women present with an advanced stage of the disease, having had symptoms for several months before visiting their GP or other healthcare professional. Furthermore, there are often delays between initial investigation and referral to a specialist, which can further impede treatment initiation.2

Earlier diagnosis can improve survival outcomes for cancer;4 however, the natural history of ovarian cancer is unknown and there is insufficient evidence to say whether the duration of symptoms before diagnosis affects overall survival, disease-specific survival, or quality of life. Nevertheless, it is generally agreed that early symptom identification has the potential to improve the prognosis of women with ovarian cancer.

In April 2011, the National Institute for Health and Care Excellence (NICE) published its first clinical guideline on the identification and initial management of ovarian cancer.1,2 The recommendations were developed by clinical and patient experts and are based on the best available evidence and stakeholder feedback; they therefore represent best clinical practice for the NHS. A key focus of the guideline is the need for primary care healthcare professionals to have greater involvement in the initial investigations for ovarian cancer to ensure that women are referred to the correct specialist teams in a timelier manner so that they can then begin treatment sooner.1,2

Identification of ovarian cancer

Although ovarian cancer is often dubbed a ‘silent killer’, a systematic review by Bankhead et al estimated that 93% of women experienced symptoms before their diagnosis.5 As the symptoms of ovarian cancer are non-specific, it can mean that women with the disease may delay going to see their doctor for a very long time before the symptoms begin to be a cause for concern. Then on initial examination, their symptoms can be attributed to a variety of health concerns, some of which are more serious than others.

The issue of non-specific symptoms can mean that GPs repeatedly ask their patients to revisit on several occasions before symptoms are recognised as significant or that patients are referred to the wrong specialist teams in secondary care. A GP in an average-sized practice may only see one case of ovarian cancer every 5 years or so, which makes recognition and early diagnosis all the more difficult. Even when the symptoms are recognised as significant, the GP has to ensure that he or she makes the correct referral (see Figure 1, below).

The NICE guideline advises GPs to consider investigating women (particularly those aged 50 years or over) who report having any of the following symptoms on a persistent or frequent basis (particularly more than 12 times a month):1,2

  • Persistent abdominal distension (often referred to as ‘bloating’)
  • Early satiety (feeling full quickly) and/or loss of appetite
  • Pelvic or abdominal pain
  • Increased urinary urgency and/or frequency.

General practitioners should also consider carrying out tests in primary care if a woman reports unexplained weight loss, fatigue, or changes in bowel habit. Appropriate assessments for ovarian cancer should be initiated in any woman aged 50 years or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS). This is because IBS rarely presents for the first time in women of this age.1,2,6

However, the above symptoms alone are not sufficient to refer a woman to secondary care on a cancer pathway. Clinical examination, including pelvic examination, remains relevant, particularly if there is obvious abdominal distension or a palpable abdominal mass.2

If ovarian cancer is not suspected, women should be advised to return to their GP if their symptoms become more frequent and/or persistent.1,2


Figure 1: Detection of ovarian cancer in primary care1,2

graph

* See also ‘Referral guidelines for suspected cancer’ (NICE Clinical Guideline 27; available at www.nice.org.uk/guidance/CG27) for recommendations about the support and information needs of people with suspected cancer.

† See ‘Irritable bowel syndrome in adults’ (NICE Clinical Guideline 61; available at www.nice.org.uk/guidance/CG61). IBS rarely presents for the first time in women of this age.

‡ An urgent referral means that the woman is referred to a gynaecological cancer service within the national target in England and Wales for referral for suspected cancer, which is currently 2 weeks.

IBS=irritable bowel syndrome

National Institute for Health and Care Excellence (NICE) (2011) CG122. Ovarian cancer: the recognition and initial management of ovarian cancer. London: NICE. Available from www.nice.org.uk/guidance/CG122 Reproduced with permission.

Initial testing

The NICE guideline advises GPs to measure serum CA125 in women whose symptoms are suggestive of ovarian cancer.1,2 Although there is no single method that will diagnose ovarian cancer definitively, the evidence shows overwhelmingly that the CA125 test is the best that is currently available.7 Approximately 80% of women with an advanced stage of ovarian cancer and 50% of those at an early stage of the disease will have raised levels of the protein.8

The recommendation to perform the CA125 test may represent a change in clinical practice for some primary care settings as the test is often used as a tumour indicator in secondary care. By offering this cost-effective test sooner and in primary care, it is hoped that women will be referred to the correct specialist settings sooner and obtain earlier diagnoses.

Following the CA125 test
The NICE guideline advises GPs to arrange for a woman to have an ultrasound of the abdomen and pelvis if her serum CA125 is 35 IU/ml or greater.1,2

Women who have either a normal CA125 level (i.e. less than 35 IU/ml) or CA125 that is 35 IU/ml or greater but with a normal ultrasound should be:1,2

  • assessed carefully for other clinical causes of symptoms and investigated if appropriate
  • advised to return to the GP if their symptoms become more frequent and/or persistent if no other clinical cause is apparent.

Compared with referring women with either an abnormal serum CA125 or ultrasound alone, this sequential combination approach reduces the number of women referred and increases the incidence of ovarian cancer in the referred population from about 1 in 157 to 1 in 26.2 Even so, this should still ensure that most women with ovarian cancer are put on the right care pathway in a timelier fashion.

Women who have an ultrasound scan that suggests ovarian cancer should be referred urgently for further investigation. This means that the woman is referred to a gynaecological cancer service within 2 weeks—the current target for suspected cancers in England and Wales.1,2

General practitioners who identify ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids) during the physical examination should refer their patients urgently (within 2 weeks) for further investigation.1,2

Implementation tools

NICE has developed the following tools to support implementation of Clinical Guideline 122 on Ovarian cancer: the recognition and initial management of ovarian cancer. The tools are now available to download from the NICE website: www.nice.org.uk/CG122

Baseline assessment tool

The baseline assessment tool is an Excel spreadsheet that can be used by organisations to identify if they are in line with practice recommended in NICE guidance and to help them plan activity that will help them meet the recommendations.

Clinical audit tools

Audit tools aim to assist organisations with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. They consist of audit criteria and data collection tool(s) and can be edited or adapted for local use.

Costing statement

The costing statement estimates the financial impact to the NHS of implementing this clinical guideline. This statement focuses on the financial impact of the recommendations that require most change in resources to implement in England.

Clinical case scenarios

These scenarios have been developed to improve and assess knowledge of the recognition of ovarian cancer and its application in practice. They illustrate how the NICE recommendations on ovarian cancer can be applied to the care of women presenting in primary care.

Slide set

The slides provide a framework for discussing the NICE guideline with a variety of audiences and can assist in local dissemination. This information does not supersede or replace the guidance itself.

Podcasts

There are two podcasts available, which cover:

  • issues for general practitioners, specifically the use of CA125 tests and how to manage patients who have negative results, and the use of clinical judgement
  • the role of lymph node assessment and systematic retroperitoneal lymphadenectomy from a consultant perspective.

Confirming the diagnosis

Once the woman is referred, the onus is on making the correct diagnosis as quickly as possible; safety and cost effectiveness are important considerations.

If ovarian cancer is suggested by ultrasound, CA125, and clinical status, a computed tomography scan of the pelvis and abdomen should be performed to establish the extent of disease and facilitate decisions concerning the appropriateness and timing of surgery.1,2 Although, the NICE guideline does not advocate magnetic resonance imaging as a routine test for assessing women with suspected ovarian cancer, this does not preclude its use in selected cases.

Histological diagnosis
Wherever possible, diagnosis of ovarian cancer should be based on histology as this is the only way of determining the cancer type and grade and will also exclude diagnoses such as tuberculosis, inflammation, fibrosis, and other infections. Different histological types of ovarian cancer require different treatments. Methods of obtaining a tissue diagnosis include needle biopsy, laparoscopy, or open laparotomy.1,2 All are invasive and therefore carry risks.

Histological diagnosis is usually made following surgery. In some cases, for example, where surgery is not feasible or where chemotherapy is the initial treatment, other options for obtaining a histological diagnosis may be considered.1,2 Cytology is generally safer than tissue biopsy but has a lower diagnostic accuracy. When it is hazardous or difficult to obtain a tissue diagnosis, the risks of such procedures need to be weighed against the potential benefits of greater diagnostic accuracy. After discussion with the woman, it may be concluded that a tissue diagnosis is not essential.

Management

The NICE guideline states that if the cancer is thought to be confined to the ovary/ovaries, a thorough surgical staging via a midline laparotomy should be performed. This should include retroperitoneal lymph node assessment (a block dissection of the pelvic lymph nodes from the pelvic side walls to the renal vessels, with its associated morbidity, is not advised).1,3 For patients with suspected advanced cancer, the objective of surgery should be the complete resection of all macroscopic disease (there was insufficient evidence to make a recommendation as to the optimal timing for primary surgery).1,3

Chemotherapy is the mainstay of initial treatment for the majority of women with ovarian cancer and previous NICE guidance concerning advanced disease remains in force.9 However, the guideline recommends that adjuvant chemotherapy should not be offered to women who have had optimal staging and have low-risk stage I disease.1,2 Although it was noted that intraperitoneal chemotherapy was possibly more effective than standard intravenous chemotherapy in advanced disease, concerns about toxicity and difficulties in administration precluded recommending this therapy.1,2

Provision of information

Healthcare professionals involved in the care of women with ovarian cancer, including those in primary care, are expected to implement the previous recommendations concerning information needs from: Improving outcomes in gynaecological cancer;10 and Improving supportive and palliative care for adults with cancer.11 The NICE guideline specifically recommends that all women with newly diagnosed ovarian cancer be given timely and relevant information (details of which can be found in the recommendations).1,2

Conclusion

The NICE guideline provides a comprehensive overview, based on expert opinions and best-available evidence, of how to recognise and manage ovarian cancer initially. As this is the first time that national guidance has been published for the NHS on this topic, it will improve the way that primary care healthcare professionals identify and treat women with ovarian cancer.

For further information and to download copies of the clinical guideline, visit: www.nice.org.uk/CG122. This webpage also includes practical tools to help healthcare professionals implement the guideline (see NICE implementation tools, below), as well as information that they can give to patients, detailing the tests and treatments that they can expect to receive.


  1. National Institute for Health and Care Excellence. Ovarian cancer: the recognition and initial management of ovarian cancer. Clinical Guideline 122. London: NICE, 2011. Available at: www.nice.org.uk/CG122
  2. National Collaborating Centre for Cancer. Ovarian cancer: the recognition and initial management of ovarian cancer. Cardiff: NCCC, 2011. Available at: www.nice.org.uk/guidance/CG122/Guidance/pdf/English
  3. Office for National Statistics. Cancer survival in England: patients diagnosed 2004?2008, followed up to 2009. Available at: www.statistics.gov.uk/statbase/product.asp?vlnk=14007
  4. Thomson C, Forman D. Cancer survival in England and the influence of early diagnosis: what can we learn from recent EUROCARE results? Br J Cancer 2009; 101 (Suppl 2): S102–S109.
  5. Bankhead C, Kehoe S, Austoker J. Symptoms associated with diagnosis of ovarian cancer: a systematic review. BJOG 2005; 112 (7): 857–865.
  6. National Institute for Health and Care Excellence. Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome in primary care. Clinical Guideline 61. London: NICE, 2008. Available at: www.nice.org.uk/CG61
  7. Myers E, Bastian L, Havrilesky L et al. Management of adnexal mass. Evid Rep Technol Assess (Full Rep) 2006; Feb (130): 1–145.
  8. Bast R Jr, Klug T, St John E et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983; 309 (15): 883–887.
  9. National Institute for Clinical Excellence. Guidance on the use of paclitaxel in the treatment of ovarian cancer. Technology Appraisal 55. London: NICE, 2003. Available at: www.nice.org.uk/guidance/TA55/Guidance/pdf/English
  10. Department of Health. Guidance on commissioning cancer services. Improving outcomes in gynaecological cancers. The manual. Available at: www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4005385
  11. National Institute for Clinical Excellence. Guidance on cancer services. Improving supportive and palliative care for adults with cancer. The manual. London: NICE, 2004. Available: www.nice.org.uk/CSGSPG