3.1 Primary care

3.1.1 SIGNS AND SYMPTOMS

Retrospective studies show that women with ovarian cancer present with non-specific symptoms including abdominal pain and bloating; changes in bowel habit, urinary and/or pelvic symptoms.^{40, 41, 42} Cachexia is uncommon and women with advanced disease often look surprisingly well. Most women with ovarian cancer present with advanced disease. On average, a GP will see only one new case every five years.⁴³ No high quality evidence was identified on symptoms or signs suggestive of early ovarian cancer. Patients who present with non-specific gastrointestinal symptoms may be misdiagnosed as suffering from irritable bowel syndrome. Evidence level 2+,2-,3

One descriptive study examined the impact of delayed referral from primary care on survival.⁴⁴ Delay in referral was not found to be a frequent occurrence and did not impact on survival.⁴⁴ Evidence level 3

GPs should include ovarian cancer in the differential diagnosis when women present with recent onset persistent non-specific abdominal symptoms (including women whose abdominal and pelvic clinical examinations appear normal).

3.1.2 BLOOD TESTS - THE ROLE OF CA125

Measurement of serum CA125 is the blood test most widely used to detect ovarian cancer. CA125 is a glycoprotein antigen. Elevated concentrations of CA125 are associated with malignant tumours of the pancreas, breast, lung, colon and ovary.⁴⁵ Menstruation and benign conditions such as endometriosis, pelvic inflammatory disease and liver disease can also be associated with elevated concentrations of CA125.⁴⁶ CA125 may also be elevated in women with ascites, pleural or pericardial effusions and in women who have had a recent laparotomy.⁴⁷ Evidence level 3,4

Approximately 80% of patients with advanced ovarian cancer have elevated concentrations of CA125. A maximum of only 50% of patients with clinically detectable stage I disease have elevated CA125 levels.⁴⁸ Despite its poor sensitivity and specificity, CA125 is most useful for detecting and monitoring non-mucinous epithelial tumours of the ovary.⁴⁹ Evidence level 3,4

No studies were identified that assessed the usefulness of the measurement of serum CA125 in women with vague abdominal symptoms hence the guideline development group cannot recommend the routine measurement of CA125.

Women with a pelvic mass should be referred to gynaecology irrespective of the CA125 test result.

3.2 Secondary care

Women referred to gynaecology with suspected ovarian cancer need ultrasound assessment. This will identify a pelvic mass and the presence of metastatic disease. Where no obvious disease is identified the dilemma for the gynaecologist is deciding whether the pelvic mass is likely to be malignant and who should operate on the patient. Prognosis in ovarian cancer correlates strongly with the ability to achieve optimal cytoreduction, which is more feasible in surgical centres with the greatest surgical experience (see section 4.4). The risk of malignancy index (RMI) scoring system can be used to predict whether the mass is malignant.

3.2.1 THE RISK OF MALIGNANCY SCORING SYSTEM

There are two scoring systems, RMI 1 and RMI 2, each of which calculates scores using ultrasound features, menopausal status and preoperative CA125 level according to the equation:

RMI score = ultrasound score x menopausal score x CA125 level in U/ml.

The original RMI 1 scoring system and the revised RMI 2 system are both outlined in Table 1.^{50, 51} The RMI 2 score gives greater weight to the ultrasound findings and menopausal status than the RMI 1 score.

Table 1: The risk of malignancy index (RMI) scoring system^{50, 51}

Four cohort studies exploring the role of RMI scores were identified.^{50, 51, 52, 53} Three of these studies compared the two RMI scores using cut-off values above 200 to indicate malignancy.^{51, 52, 53} The RMI 2 score was more sensitive than the RMI 1 system with results of 74 to 80% at a specificity of 89 to 92% and positive predictive values around 80%.^{51, 52, 53} Evidence level 2+

Other scoring methods have been used to estimate the risk of malignancy in a pelvic mass.^{54, 55} A complex logistical regression model performed less well than the RMI scoring system.⁵⁴ Colour flow and pulsed wave Doppler techniques show limited clinical application in isolation.⁵⁵ Evidence level 2+

The RMI scoring system is the method of choice for predicting whether or not an ovarian mass is likely to be malignant. Women with an RMI score >200 should be referred to a centre with experience in ovarian cancer surgery.

3.2.2 VALUE OF COMPUTERISED TOMOGRAPHY (CT) AFTER ULTRASOUND

The use of RMI scoring is not appropriate when obvious metastatic disease has been identified by ultrasound. In this situation the gynaecologist may wish to obtain a CT scan to obtain more information on the extent of metastatic disease. It is the view of the guideline development group that CT is better than US for retroperitoneal assessment, and the detection of omental and peritoneal disease. If the gynaecologist wishes to assess the extent of involvement of the peritoneum, omentum and retroperitoneum prior to surgery a CT scan should be used.