Ovarian cancer although relatively rare is often fatal. The GP’s role is vital not only in diagnosis but also in supporting patients, says Dr John Donald
Epithelial ovarian cancer is described as a ‘silent killer’ as in over 60% of cases advanced disease is found at initial presentation.1
Ovarian cancer is the fourth most common cancer in women. Some 4.6% of all newly diagnosed cancers are ovarian cancer. In Scotland, there are approximately 600 new cases and around 400 women die from the disease each year.2
The overall 5-year survival rate is 30%, and this rate has not changed significantly in the past 20 years.3 Survival is dependent on the stage of cancer at initial presentation. Treatment is not usually curative and while stage I disease has a 5-year survival rate of 85%, the 5-year survival rate for stage IV disease is only 10%.4
The disease, the aetiology of which is unknown, is rare in girls and women below the age of 30 years;2 the incidence increases with age until a maximum is reached in the sixth decade.
It is against this backdrop that SIGN has developed an evidence-based guideline, Epithelial ovarian cancer, for primary and secondary care.
Most of the guideline’s recommendations for GPs are not supported by randomised controlled trials; therefore they rely on evidence at the lower end of the scale, mainly Cs, Ds and good practice points.
However, this does not detract from the guideline because a great deal of the supportive work that GPs carry out is often based on clinical experience. Figure 1 (below) shows the key to evidence statements and grades of recommendation.
|Figure 1: Key to the evidence statements and grades of recommendation|
Diagnosis presents a real difficulty for GPs because the incidence of ovarian cancer is very low – a GP is likely to see only one new case every 5 years 5 – and because women with ovarian cancer present with non-specific symptoms. These include abdominal pain and bloating, changes in bowel habit, and urinary and/or pelvic symptoms.6,7
The guideline development group found no good evidence on specific symptoms and signs suggestive of early ovarian cancer.
GPs should include ovarian cancer in the differential diagnosis (see Figure 2, below) when women present with recent-onset, persistent, non-specific abdominal symptoms (including women whose abdominal and pelvic clinical examinations appear normal). (Good practice point)
|FIgure 2: Extracts from the quick reference guide|
Identifying women at high risk and screening
The guideline emphasises the importance of family history in identifying women who are at increased risk of ovarian cancer.8 The estimate of lifetime risk for individuals who have one first-degree relative with ovarian cancer is 2-5 times the population risk.9,10
Women whose family history identifies them as at high risk (Box 1, below) should be offered referral to a clinical genetics service for assessment and confirmation of their family history. (Good practice point)
|Box 1: Defining women at high risk of ovarian cancer using family history|
Women are at high risk of ovarian cancer if they have a first degree relative (mother, father, sister, brother, daughter or son) affected by cancer within a family that meets one of the following criteria:
The BRCA1 and BRCA2 gene mutations that predispose to cancer are estimated to account for only a small proportion, perhaps 5 to 10%, of all ovarian cancers.9
The guideline states, however, that there is no strong evidence that presymptomatic screening of women at high risk is effective in detecting tumours at an early stage.11-13
It also warns that screening women at high risk can increase anxiety,14-16 and that the currently available screening tools – grey scale ultrasound (with or without Doppler), CA125 and pelvic examination or combinations of these – are not accurate enough to allay this.16-17
Under this section the guideline makes two clear recommendations for GPs.
Close collaboration between primary care and specialist cancer genetics services should be developed and encouraged so that genetic cancer risk assessment can be carried out efficiently. (Good practice point)
Primary care clinicians should formally enquire about the woman’s family history. (Good practice point)
The guideline also recommends that easily accessible guidelines for assessing family history should be available for GPs, perhaps in the form of an education pack.18
The role of CA125 testing
CA125 is a glycoprotein antigen, elevated concentrations of which are associated with malignant tumours of the pancreas, breast, lung, colon and ovary.19
However, menstruation and several benign conditions, such as endometriosis and pelvic inflammatory disease can also be associated with raised levels of CA125.20 Moreover, only 50% of patients with clinically detectable stage I disease have elevated CA125 levels.21
This means that the test has poor specificity and sensitivity and cannot be recommended as a routine test in women presenting with vague abdominal symptoms.
Women with a pelvic mass should be referred to gynaecology irrespective of the CA125 test result. (Grade D)
Women who have a high risk of ovarian cancer can be offered prophylactic oophorectomy.This may also reduce the risk of breast cancer because most women at increased risk of ovarian cancer are also at increased risk of breast cancer.22,23 This is particularly relevant for women who are carriers of BRCA1 and BRCA2 mutations.
The guideline emphasises the importance of counselling, support and information for women making a decision about prophylactic oophorectomy and those who undergo surgery.
Follow up and support
Although CA125 measurement is not recommended as a diagnostic tool, it is a very useful marker for relapse in the follow up of ovarian cancer,24,25 because relapse can occur without clinical symptoms or ultrasound abnormalities.
Although follow up will be arranged principally by secondary care, the primary care team should be made aware of the follow up protocol for those patients not in trials. (Good practice point)
A typical patient will develop relapsed disease requiring repeated courses of chemotherapy, and relapsed disease is invariably fatal. A diagnosis of ovarian cancer obviously has a huge impact on patients and their carers, and prospects for improving survival lie with optimal management after initial presentation.
When cure is not possible, the goal for health professionals must be to ensure that the woman has a good quality of life. This will involve judicious use of surgery and chemotherapy, providing information and support when needed and involving a specialist palliative care team.
Management requires a multidisciplinary approach that may include primary care staff, medical and clinical oncologists, gynaecologists, specialist nurses and community nurses, allied health professionals, geneticists, pathologists, specialists in laboratory medicine, pharmacists, radiologists and palliative care specialists.26
The guideline particularly emphasises the role of the specialist palliative care team because studies have shown that their involvement results in patients spending more time at home and having better symptom control, greater satisfaction for patients and carers and more patients dying where they wished.27
Although the greater part of this guideline is aimed at secondary care treatment, it emphasises the key role of the GP in diagnosis and in providing ongoing support and information. While studies show that patients prefer written to verbal information, both are important in helping patients and their carers to come to terms with this often fatal disease. It is therefore incumbent on GPs to know how and where to obtain this information and to know how to obtain support from agencies that offer assistance.
SIGN 75. Epithelial Ovarian Cancer. A National Clinical Guideline can be downloaded from www.sign.ac.uk
- Junor EJ, Hole DJ, McNulty L. Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients. Br J Obstet Gynaecol 1999; 106(11): 1130-6.
- Scottish Cancer Intelligence Unit.Trends in cancer survival in Scotland 1971-1995. Edinburgh: Information and Statistics Division, 2000. www.isdscotland.org/isd/files/trends_1971-95.pdf
- Gatta G, Lasota MB, Verdecchia A. Survival of European women with gynaecological tumours, during the period 1978-1989.Eur J Cancer 1998; 34(14): 2218-25.
- Kristensen GB, Trope C. Epithelial ovarian carcinoma. Lancet 1997; 349(9045): 113-7.
- Scottish Cancer Information Unit. Cancer registration statistics Scotland 1986-1995. Edinburgh:Information and Statistics Division,1998.
- Olson SH, Mignone L, Nakraseive C et al. Symptoms of ovarian cancer. Obstet Gynecol 2001; 98(2): 212-7.
- Goff BA, Mandel L, Muntz HG, Melancon CH. Ovarian carcinoma diagnosis. Cancer 2000; 89(10): 2068-75.
- Haites NE, Black R, Campbell H et al. Guidelines for regional genetic centres on the implementation of genetic services for breast, ovarian and colorectal cancer families in Scotland. CME Journal of Gynaecologic Oncology 2000; 5(3): 291-307.
- Thompson D, Easton DF. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002; 94(18): 1358-65.
- Bell R, Petticrew M, Luengo S, Sheldon TA. Screening for ovarian cancer: a systematic review. Health Technol Assess 1998; 2(2): 1-84.
- NHS Executive. Guidance on commissioning cancer services: improving outcomes in gynaecological cancer: the research evidence. London:The Executive; 1999.
- Taylor L, Schwarz H. Identification of a soluble OX40 isoform: development of a specific and quantitative immunoassay. J Immunol Methods 2001; 255(1-2): 67-72.
- Moller P, Borg A, Heimdal K et al. The BRCA1 syndrome and other inherited breast or breastovarian cancers in a Norwegian prospective series. Eur J Cancer 2001; 37(8): 1027-32.
- Erlick Robinson G, Rosen BP, Bradley LN et al. Psychological impact of screening for familial ovarian cancer: reactions to initial assessment. Gynecol Oncol 1997; 65(2): 197-205.
- Cull A, Fry A, Rush R, Steel CM. Cancer risk perceptions and distress among women attending a familial ovarian cancer clinic. Br J Cancer 2001; 84(5): 594-9.
- Pernet AL,Wardle J, Bourne TH et al.A qualitative evaluation of the experience of surgery after false positive results in screening for familial ovarian cancer. Psycho-oncology 1992;1: 217-33.
- Wardle J, Pernet A, Collins W, Bourne T. False positive results in ovarian cancer: one year followup of psychological status. Psychol Health 1994: 10(1): 33-40.
- Watson E, Clements A,Yudkin P et al. Evaluation of the impact of two educational interventions on GP management of familial breast/ovarian cancer cases: a cluster randomised controlled trial. Br J Gen Pract 2001; 51(471): 817-21.
- Bast RC Jr, Klug TL, 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(45): 883-7.
- Daoud E, Bodor G. CA-125 concentration in malignant and non-malignant disease. Clin Chem 1991; 37(11): 1968-74.
- Jacobs I, Bast RC Jr. The CA 125 tumourassociated antigen: a review of the literature. Hum Reprod 1989; 4(1): 1-12.
- Kauff ND, Satagopan JM, Robson ME et al. Riskreducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002; 346(21): 1609-15.
- Rebbeck TR, Lynch HT, Neuhausen SL et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002; 346(21): 1616-22.
- Rustin GJ, Nelstrop AE, Tuxen MK, Lambert HE. Defining progression of ovarian carcinoma during follow-up according to CA 125: a north Thames Ovary Group Study. Ann Oncol 1996; 7(4): 361-4.
- Van der Berg ME, Lammes FB,Verweij J.The role of CA 125 in the early diagnosis of progressive disease in ovarian cancer. Ann Oncol 1990; 1(4): 301-2.
- Junor EJ, Hole DJ, Gillis CR. Management of ovarian cancer: referral to a multidisciplinary team matters. Br J Cancer 1994; 70(2): 363-70.
- Hearn J. Higginson IJ. Do specialist palliative care teams improve outcomes for cancer patients? A systematic literature review. Palliat Med 1998; 12(5): 317-32.