Ovarian cancer is the 6th most common cancer in the UK, with approximately 7500 new cases diagnosed annually, or 21 per day. 92% of cases arise in the ovary, with 8% in the fallopian tube. For that reason, there has been a trend in modern gynaecological surgery to remove fallopian tubes as part of a sterilisation procedure, or when performing a hysterectomy with ovarian conservation.
Diagnosing Ovarian Cancer
Around 1 in 50 women in the UK population will develop ovarian cancer in their lifetime, however, those who inherit one of the BRCA genetic mutations have a significantly increased risk (39% of women who carry BRCA1 and 11-17% of women who carry BRCA2) of ovarian cancer. Whilst there is no established screening programme for such women, they may be referred for prophylactic removal of their ovaries and fallopian tubes to reduce their risk of ovarian cancer once their family is complete.
There is no established screening programme for ovarian cancer, and therefore diagnosis is based on recognising clinical symptoms and signs along with appropriate investigations. NICE (National Institute for Health and Clinical Excellence) have produced guidelines for the recognition of ovarian cancer, as have the BGCS (British Gynaecological Cancer Society) and the RCOG (Royal College of Obstetricians and Gynaecologists).
NICE recommends urgent referral to secondary care gynaecology on a ‘two-week wait’ basis if ascites or a pelvic mass (which is not obviously fibroids) is detected. Ovarian cancer can also be associated with several non-specific symptoms – abdominal distension/bloating, early satiety, loss of appetite, pelvic or abdominal pain, increased urinary frequency or urgency, unplanned weight loss, fatigue or changes in bowel habit. Should a number of these symptoms be present on a frequent or persistent basis, then a blood test (CA125) should be measured. CA125 is a marker that is raised in some cases of epithelial cancer. If the result is above the normal range (35 U/mL) then a pelvic ultrasound scan should be requested urgently. If both are abnormal then urgent referral to secondary care is indicated.
A ‘Risk of Malignancy Index’ (RMI) can be calculated based on the ultrasound appearances of the ovaries, the menopausal status and the CA125 value, using the formula R = U x M x CA125, where U is the ultrasound score (0, 1 or 3 depending on the characteristics of the ovarian mass), M is the menopausal status (1 if premenopausal, 3 if postmenopausal) and CA125 is the absolute value of the CA125.
A result of less than 200 (250 in some centres) suggests a low risk of malignancy and the case can be managed by a general gynaecologist. If the ovarian cyst is asymptomatic, simple, <5cm, unilocular and unilateral, then conservative management with surveillance is appropriate, otherwise surgery (removal of the affected ovary and fallopian tube) is indicated.
In many cases, this would be bilateral (removal of both ovaries), however, this will result in loss of fertility and menopause will ensue. Careful discussion with the woman and individualised decision-making are therefore paramount, with comprehensive documentation required to record the discussion and decision-making process.
If the RMI is elevated, then further imaging such as a CT scan would be performed before referral for a multi-disciplinary review in a gynaecological oncology centre. If there was thought to be a high likelihood of ovarian cancer, then a full staging laparotomy by a specialist gynaecological oncologist is indicated, otherwise, a pelvic clearance (hysterectomy and removal of both ovaries and fallopian tubes, omentectomy and peritoneal cytology) by a suitable gynaecologist is required.
Curing Ovarian Cancer
The standard principle in ovarian cancer is to offer surgical debulking of disease – the removal of all areas of cancer (full staging laparotomy). Such surgery can be complex and include bowel resection, liver mobilisation and peritoneal stripping. These operations carry a high morbidity and therefore initial chemotherapy can be employed (neo-adjuvant chemotherapy) to reduce the volume of ovarian disease and therefore reduce the extent of surgery that is required. This is often appropriate if there are areas of disease not amenable to surgery, or if it is thought that the woman’s medical comorbidities would prevent aggressive surgery. If neoadjuvant chemotherapy is to be used then a biopsy of the tumour to confirm the diagnosis is required.
If there is a lower likelihood of ovarian malignancy, more limited surgery can be performed. It is important for the woman to understand that further surgery may be required should a diagnosis of malignancy be confirmed following the procedure. Some centres would employ a ‘frozen section’ technique – the abnormal ovary is removed and sent immediately for a rapid analysis – provisional results can be communicated to the operating theatre within an hour, and then the surgery is modified according to the results of the frozen section.
Once the final pathology results following surgery are known, there is a further multi-disciplinary discussion and further management is planned. This often includes chemotherapy. If the aim of surgery is to resect all visible (macroscopic) diseases, then the aim of chemotherapy is to reduce the invisible (microscopic) disease.
Careful follow-up is required, often following local guidance with an emphasis on symptoms, though most centres will monitor CA125. Recurrence of disease is often managed with chemotherapy as opposed to repeated surgery.
Other CA125 Results
In younger women, germ cell tumours are more common. In addition to CA125, germ cell markers (AFP, HCG and inhibin) can be used to establish a diagnosis. Fertility-sparing surgery (removal of the affected ovary without pelvic clearance) is usually possible, and adjuvant chemotherapy in high-risk cases is employed.
Other conditions such as endometriosis and pelvic inflammatory disease can present with both a pelvic mass and a raised CA125. If there is diagnostic uncertainty, further imaging such as MRI scans may help to characterise the ovarian mass, and an additional blood test, HE4 (human epididymis protein 4) is often not raised in benign disease (endometriosis and pelvic inflammatory disease.
If the CA125 result is abnormal, but the scan fails to show any ovarian abnormalities, then it is important to remember that the CA125 test is non-specific – there are many conditions that can cause an elevated CA125, so further surveillance and imaging studies are indicated.