CA125 in the diagnosis of ovarian cancer: the art in medicine Dr Marcia Hall Consultant Medical Oncology Mount Vernon Cancer Centre Hillingdon Hospital Wexham Park Hospital
Epidemiology Ovarian cancer is the 5th most common cancer in women in the UK Over 6700 new cases are diagnosed each year, accounting for approximately 1 in 20 cases of cancer in women Around 4300 women die from ovarian cancer each year in the UK, representing 6% of all cancer deaths in women
Background Ovarian cancer is a challenge to diagnose because of the nonspecific nature of symptoms and signs Most women are diagnosed with advanced disease (stages II IV) Image reproduced by kind permission of Dr Sue Barter
Two types ovarian cancer Type I: lower grade more differentiated malignancies arising from the ovary such as endometrioid, mucinous, clear cell Type II: higher grade less well differentiated malignancies arising from either tube of ovary or peritoneum serous, mixed serous and poorly differentiated endometioid, undifferentiated etc.
Key priorities for implementation Areas identified as key priorities for implementation are: Awareness of symptoms and signs Asking the right question first tests Malignancy indices Tissue diagnosis The role of systematic retroperitoneal lymphadenectomy Adjuvant systemic chemotherapy for stage I disease Support needs of women with newly diagnosed ovarian cancer Guideline section Detection in primary care Establishing the diagnosis in secondary care Management of suspected early (stage I) ovarian cancer Support needs Care setting Primary Secondary Secondary or Tertiary All settings
Awareness of symptoms and signs: 1 Refer the woman urgently if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids)
Awareness of symptoms and signs: 2 Carry out tests in primary care if a woman (especially if 50 or over) reports having any of the following symptoms on a persistent or frequent basis particularly more than 12 times per month: persistent abdominal distension (women often refer to this as bloating ) feeling full (early satiety) and/or loss of appetite pelvic or abdominal pain increased urinary urgency and/or frequency
Awareness of symptoms and signs: 3 Consider carrying out tests in primary care if a woman reports unexplained weight loss, fatigue or changes in bowel habit Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS) Advise any woman who is not suspected of having ovarian cancer to return to her GP if her symptoms become more frequent and/or persistent
IBS presenting for the first time in patients over the age of 50 is very unlikely to be the cause for a change in bowel habit
Detection in primary care Ascites and/or pelvic or abdominal mass Women presents to GP GP assesses symptoms Tests in primary care Suspicion of ovarian cancer Support and information Urgent referral: assessment in secondary care
48% 15% 29%
Family history Hereditary Breast Ovary syndrome BRCA carriers
First tests Measure serum CA125 in primary care in post menopausal women with symptoms that suggest ovarian cancer If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis.
First tests in primary care Measure serum CA125 35 IU/ml or greater Less than 35 IU/ml Ultrasound of abdomen and pelvis Normal Assess carefully: are other clinical causes of symptoms apparent? Suggestive of ovarian cancer Yes No Refer urgently Investigate Advise to return to GP if symptoms become more frequent and/or persistent
Risk of Malignancy Index (RMI)
Malignancy indices Perform ultrasound Calculate a risk of malignancy index I (RMI I) score Refer all women with an RMI I score of 250 to specialist team Image reproduced by kind permission of Dr Sue Barter
Premenopausal Mount Vernon Cancer Network Complex masses are frequently luteal, dermoid or endometrioma Women should be referred under 14 days only if the imaging is sufficiently suspicious Advice from USS reports should be clear stating Cancer Alert Significant Abnormality alerts should not automatically be referred under 14 Days
Postmenopausal Women Mount Vernon Cancer Network Unilocular ovarian cysts (no septations or solid areas) are likely to be benign and can be referred non urgently providing CA125 is not elevated All other ovarian masses on USS or pelvic masses should be referred under 14 days New diagnosis of IBS (recent change) is unusual in women over the age of 50
What is CA125? Glycoprotein produced at low levels in all Elevated in conditions where there is irritation of the peritoneal membranes eg. Any condition resulting in ascites TB, cardiac failure, hepatic insufficiency Elevated temporarily in menstrual cycle and pregnancy Significantly elevated in endometriosis
So why bother with CA125? Mount Vernon Cancer Network No good on its own (esp. for population screening) Marginal rise difficult to interpret Very useful to add weight to suspicion of ovarian cancer Urgency of referral Symptoms or mass Counselling patient Always do in postmenopausal patients with suspicious symptoms Consider very carefully in premenopausal much less likely to be helpful and will probably raise more anxieties than help
CA 125 and ovarian cancer 90% patients with ovarian cancer will have elevated CA125 (especially those with papillary serous subtype ~ 75% OC population) Remainder usually have endometrioid, mucinous or clear cell subtypes more likely to present with abdomino/pelvic masses and less peritoneal spread thus less likely to have elevated CA125
Screening for OC Effect of screening on ovarian cancer mortality in randomised screening trial in US HARMFUL!! UKCTOCS study completed recruitment results awaited
Referral Criteria Mount Vernon Cancer Network Palpable postmenopausal mass Complex postmenopausal mass on USS Suspicious premenopausal mass Clinical suspicion by combination of: GI/abdominal symptoms Ascites Family history CA125
Indeterminate adnexal mass