Ovarian cancer is the second most common gynaecological cancer after uterine.
Ovarian cancer is relatively rare before the age of thirty, with incidence increasing with age, highest in those aged 75-79.
It is less common in multiparous women and those who have used the combined oral contraceptive.
It often presents non-specific symptoms and as such if often diagnosed at an advanced stage (60% diagnosed at stage III/IV. Recognition of these non-specific symptoms and appropriate investigations may help to catch the disease at earlier stages.
There are approximately 7,400 cases of ovarian cancer in the UK each year.
It is the sixth most common cancer in women. Incidence is highest in women aged 75-79.
In the UK, ovarian cancer is more common white women when compared to those of asian or black ethnicity.
Ovarian cancers can be classified as epithelial or non-epithelial in origin.
Epithelial carcinomas account for about 90% of ovarian cancers. The majority are thought to arise from the ovarian surface epithelium or the distal fallopian tube.
There are a number of subtypes:
Non-epithelial carcinomas account for around 10% of ovarian cancers. In those of black and asian heritage - where epithelial carcinomas are rarer, germ cell tumours account for a significant proportion of ovarian cancers.
There are many types including:
Risk of ovarian cancer increases with number of ovulatory cycles and age.
It is thought that risk of ovarian cancer is proportional to the number of ovulatory cycles a women has in a lifetime. As such the following are risk factors:
Other hormonal risk factors include:
Ovarian cancer is often asymptomatic in early stages, as such it is frequently diagnosed late.
Patients can present with features of complications such as pleural effusions or bowel obstruction (adhesional). It may also present with DVT and occasionally a paraneoplastic syndrome (e.g. paraneoplastic cerebellar degeneration).
CA125 is a glycoprotein and tumour marker used in the diagnosis of ovarian cancer.
The normal range is 0-35 IU/ml, though levels are known to vary with age and between ethnic groups. Its measurement forms a core component of the suspected ovarian cancer work-up and is used in the Risk of Malignancy Index (see below).
It is raised in around 80% of patients with ovarian cancer, however this is closer to 50% in those with stage 1 disease.
CA125 is a relatively non-specific tumour marker and may be raised in a number of malignancies including pancreas, breast, lung, colon, endometrial, epithelial ovarian cancer.
In addition CA125 is raised in a number of benign conditions including endometriosis, liver disease, pelvic inflammatory disease and the first trimester of pregnancy.
Diagnostic tests typically begin with USS and CA125 often followed by CT scan.
Diagnosis of ovarian cancer can be via a number of routes. Commonly investigations will follow a presentation to GP with persistent non-specific symptoms.
There are two national guidelines from SIGN (2013) and NICE (2011). Each has subtle differences in advice. Here we describe the pathway
A Ca125 and USS are typically the first investigations ordered in patients with suspected ovarian cancer. These can be used to calculate the risk of malignancy score.
The RMI score is calculated from the CA125, menopausal status and ultrasound findings. It is the product of the three scores. RMI = U x M x CA125
A number of RMI scores exist - primarily with difference in how ultrasound findings are scored. NICE and SIGN guidelines advise RMI 1 score is used.
Local services may have different RMI cut-offs regarding discussion at specialist MDT (NICE advise > 250, SIGN advise >200), with other patients being managed at local centres. Additional investigations are likely to be ordered including CT scan, BHCG, AFP, LDH, Ca19-9 and CEA.
In particular, younger women (e.g. <40) AFP and BHCG may identify those with non-epithelial ovarian cancer.
Depending on patient findings and MDT discussion many further tests may be ordered. This may include gastroscopy, colonoscopy, hysteroscopy, mammography and biopsy.
Final diagnosis is often obtained during surgery after appropriate MDT discussion. In cases where cytotoxic chemotherapy is proposed prior to surgery a histological sample is normally attained before treatment is commenced. This is ideally by percutaneous image-guided biopsy.
The International Federation of Gynecology and Obstetrics (FIGO) staging system (2014 revision) is commonly used to stage ovarian cancer.
Management of ovarian cancer is primarily through surgery and chemotherapy.
Management of ovarian cancer is enormously complex and depends on a myriad of factors. Management is decided on a case by case basis, and guided by specialist MDTs. Here we will discuss the general management principles for epithelial ovarian cancer.
Surgery (for patients who are fit) may be used to confirm diagnosis, stage disease and remove tumour bulk. Intra-operative frozen section can be used to help establish the likely diagnosis
The goal is normally to remove all visible tumour, but where this is not possible as much tumour burden is removed (optimal cytoreduction).
In early disease (stage 1a, grade 1/2), there can at times be discussion regarding fertility preserving surgery, but this has a risks associated.
In more advanced disease surgery may follow neoadjuvant chemotherapy or be used as the primary managment.
Adjuvant chemotherapy is commonly used. This is often using Carboplatin monotherapy or Carboplatin & Paclitaxel.
Chemotherapy can often be omitted in early disease, confined to the ovaries (stage IA, IB), with optimal surgical staging and low grade (grade 1/2).
In more advanced disease (stage IC or above) and high grade (grade 3) it is normally used. In more advanced disease neoadjuvant chemotherapy may be used prior to delayed surgery.
When diagnosed at its earliest stage, 98% survive a year or more.
However this falls to 54% when diagnosed at the latest stage - highlighting the significance of the issue of late diagnosis.
Patients who are younger at diagnosis have better survival. Around 90% of those aged 15-39 will survive five years or more.
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