Diagnosis and staging
Presentation: screening and initial diagnostics
More than 70% of women with newly diagnosed ovarian cancer present with an advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) disease.
This is due to the biology and clinical behaviour, which typically is associated with locoregional dissemination throughout the peritoneal cavity resulting in symptoms related to the spread of disease. Some women present with symptoms relating to an enlarging pelvic mass, leading to pelvic discomfort and urinary and bowel symptoms but many have a non-specific pattern of symptoms, such as abdominal bloating and distention with pain, and loss of appetite (2).Management and prognosis are determined by stage at presentation, histological grading, and patients' performance and nutritional status. In most women the underlying cause of the tumour is unknown but previous breast cancer, nulliparity, a history of endometriosis, and long-term use of hormonal replacement therapy are associated with an increased incidence of ovarian cancer. Around 10% of all ovarian cancers, higher in high-grade serous tumours, have a hereditary component with the vast majority being related to mutations of the BRCA1 and BRCA2 genes. There is also an association with hereditary non-polyposis colorectal cancer (Lynch syndrome). Prolonged use of combined oral contraceptive medication, high parity, and breastfeeding are associated with a reduced risk, as well as a history of tubal ligation and hysterectomy.
There is no conclusive evidence that screening for sporadic ovarian cancer is associated with a survival benefit. The American Prostate, Lung, Colorectal and Ovarian (PLCO) randomized cancer screening trial using annual cancer antigen 125 (CA125) and transvaginal ultrasound scanning (TVUS) showed no reduction in mortality in asymptomatic postmenopausal women, and false-positive results were associated with complications (3).
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) trial randomized over 200,000 women to observation alone, multimodal screening (MMS) testing with an algorithm based on serial values of CA125 and follow on TVUS for an abnormal result, or serial TVUS alone. No reduction in mortality was seen in the primary analysis but a possible reduction in mortality after exclusion of prevalent cases after 7 years of follow-up was shown. Long-term data and costeffectiveness data are still awaited (4).Women with symptoms suspicious of ovarian cancer should have a serum CA125 measured and a pelvic ultrasound scan. For women with a pelvic mass, a risk of malignancy index (RMI) score of 250 or greater suggests malignancy, and is a helpful diagnostic tool. RMI combines three presurgical features: serum CA125, menopausal status (M), and ultrasound (U) score. The RMI is a product of the U score (score of 1-3), the menopausal status (premenopausal status =1, postmenopausal =3), and the serum CA125 level (IU/ mL): RMI = U ? M ? CA125 (5). A score over 200 indicates a high risk of malignancy. The Risk of Ovarian Malignancy Algorithm (ROMA) is an alternative tool that incorporates human epididymis secretory protein 4 (HE4) and CA125. It appears to be helpful, especially in younger patients, where endometriosis and infections may cause elevation of CA125 levels in the absence of malignant disease (6).
FIGO staging of epithelial ovarian and fallopian tube cancers
The FIGO surgical staging system is most commonly used for ovarian cancer. Recent changes to the FIGO classification (Table 64.1) have been made to take account of the impact of lymph node
Table 64.1 FIGO classification of epithelial ovarian and fallopian tube cancers
| FIGO staging 2013 | Description |
| Stage I. Tumour confined to ovaries or fallopian tube(s) | |
| Stage IA | Tumour limited to one ovary (capsule intact) or fallopian tube; no tumour on ovarian or fallopian tube surface; no malignant cells in the ascites or peritoneal washings |
| Stage IB | Tumour limited to both ovaries (capsules intact) or fallopian tubes; no tumour on ovarian or fallopian tube surface; no malignant cells in the ascites or peritoneal washings |
| Stage IC1 | Tumour limited to one or both ovaries or fallopian tubes, with surgical spill |
| Stage IC2 | Tumour limited to one or both ovaries or fallopian tubes, with capsule ruptured before surgery or tumour on ovarian or fallopian tube surface |
| Stage IC3 | Tumour limited to one or both ovaries or fallopian tubes, with malignant cells in the ascites or peritoneal washings |
| Stage II. Tumour involves one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or primary peritoneal cancer | |
| Stage IIA | Extension and/or implants on uterus and/or fallopian tubes and/or ovaries |
| Stage IIB | Extension to other pelvic intraperitoneal tissues |
| Stage III. Tumour involves one or both ovaries or fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes. | |
| Stage IIIA1 Stage IIIA1(i) Stage IIIA1(ii) | Positive retroperitoneal lymph nodes only (cytologically or histologically proven) Metastasis up to 10 mm Metastasis more than 10 mm |
| Stage IIIA2 | Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes |
| Stage IIIB | Macroscopic peritoneal metastasis beyond the pelvis up to 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes |
| Stage IIIC | Macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumour to capsule of liver and spleen without parenchymal involvement of either organ) |
Imaging modalities and their value in decision-making processes
The management of ovarian cancer is based on a combination of clinical, pathological, biochemical, and radiological factors. Conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) are key staging investigations as they define the extent of disease and identify complicating factors such as renal obstruction or pulmonary emboli that might alter overall management. However, conventional imaging has not yet been shown to predict the operability of advanced ovarian cancer (8). For example, small-volume diffuse disease may be missed on imaging but operability also depends on other factors such as variations in surgical expertise and support facilities. Novel imaging modalities to improve the ability to predict operability, such as diffusion- weighted MRI, are currently being evaluated (9). Routine use of other specialized imaging techniques such as positron emission tomography (PET) CT (Figure 64.1) adds little extra information although it is helpful in assessing patients for surgical debulking of relapsed disease, where it may identify thoracic lymph node involvement or more diffuse inoperable disease (10).