Ovarian Cancer

Ovarian cancer is the leading cause of gynaecological cancer mortality. Symptoms are insidious and non-specific, no effective population-based screening programme exists, and most cases are diagnosed at an advanced stage.

High-grade serous carcinoma is the commonest and most clinically significant histological subtype. It frequently originates from the distal fallopian tube rather than the ovary, a relatively recent shift in understanding that directly informs risk-reducing surgery.

Management combines cytoreductive surgery and platinum-based chemotherapy.

Genetic risk assessment is integral to evaluation, because a substantial proportion of cases are attributable to an inherited pathogenic mutation.

Pathophysiology and risk factors

• Epithelial ovarian cancer accounts for the substantial majority of ovarian malignancy. High-grade serous cancers frequently arise from the fimbrial end of the fallopian tube rather than from the ovarian surface epithelium, as was historically believed. Malignant cells then seed onto and involve the ovary.
• This tubal origin underlies the growing practice of opportunistic salpingectomy (removal of the fallopian tubes alone, preserving ovarian hormonal function) as risk reduction in appropriate contexts.
• BRCA1 and BRCA2 pathogenic mutations account for a substantial proportion of ovarian cancer cases, a notably higher proportion than for breast cancer. Confirmed carriers face a substantially elevated lifetime ovarian cancer risk.
• Every woman with epithelial ovarian cancer should therefore have genetic counselling and testing. The result guides her own treatment (including eligibility for targeted PARP inhibitor therapy) and family cascade testing and risk-reduction counselling for relatives.
• Other risk factors are increasing age, nulliparity, early menarche and late menopause. These reflect cumulative ovulatory cycles, given the proposed "incessant ovulation" mechanism of malignant transformation.
• Endometriosis is specifically associated with the endometrioid and clear cell epithelial subtypes.
• Factors that reduce cumulative ovulatory cycles, including combined hormonal contraceptive use, pregnancy, and breastfeeding, are associated with reduced risk.

• Early-stage ovarian cancer is frequently asymptomatic or produces only vague, non-specific symptoms. This contributes to advanced-stage diagnosis in the great majority of affected women.
• Symptoms, when present, include bloating, early satiety, abdominal or pelvic pain, and urinary frequency or urgency. Each is common and non-specific individually. The persistent, frequent occurrence of this cluster, particularly when new and lasting weeks, warrants consideration of ovarian cancer.
• More advanced disease presents with a palpable abdominal or pelvic mass and abdominal distension from ascites. Bowel obstruction symptoms may reflect peritoneal disease. Unintentional weight loss and generalised fatigue are further systemic features.
• Disease disseminates throughout the peritoneal cavity. This accounts for the frequent presentation with diffuse abdominal symptoms and ascites rather than a localised, discrete picture.
• Diagnostic delay is substantial. Maintain suspicion in any woman, particularly of relevant age, with new, persistent, otherwise unexplained bloating, abdominal or pelvic pain, or altered bowel habit. Investigate promptly rather than attributing symptoms to a more common, benign gastrointestinal cause.

• Pelvic examination with pelvic ultrasound is the initial diagnostic approach for any woman with symptoms suggesting ovarian cancer. Abdominal ultrasound assesses more extensive disease where relevant.
• Serum CA-125 is combined with ultrasound findings and menopausal status in a structured risk of malignancy index. This supports risk stratification and the decision to refer for specialist gynaecological oncology assessment.
• CA-125 can be normal in a meaningful proportion of early-stage cases and elevated in numerous benign conditions. Never rely on it in isolation to confirm or exclude the diagnosis.
• Cross-sectional imaging, typically computed tomography of the chest, abdomen, and pelvis, stages the disease. It characterises the extent of disease and informs treatment, particularly the assessment of resectability for surgical planning.
• Definitive histological diagnosis is generally established by surgical resection where primary surgery is planned. For more advanced disease where neoadjuvant treatment is planned, use image-guided or laparoscopic biopsy. Histological subtyping and grading inform management.
• Genetic counselling and testing for BRCA1 and BRCA2 mutations (increasingly with a broader gene panel) is recommended for every woman with epithelial ovarian cancer, regardless of family history. A substantial proportion of cases reflect an inherited pathogenic mutation, and the result informs treatment selection and family counselling.

• Primary cytoreductive (debulking) surgery is central to management in the substantial majority of cases. It aims for maximal, ideally complete, macroscopic resection of all visible disease, because the extent of cytoreduction achieved is directly related to overall prognosis.
• Surgery typically comprises total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and surgical staging, with resection of any other sites of visible disease as required.
• Neoadjuvant chemotherapy followed by interval cytoreductive surgery is an alternative for women with more extensive disease where primary optimal cytoreduction is not considered feasible. It aims to reduce disease burden and improve resectability.
• Adjuvant chemotherapy, typically a platinum agent combined with a taxane, follows surgery in the great majority of cases beyond the earliest, most favourable stage. There is a substantial risk of microscopic residual disease even after apparently complete macroscopic cytoreduction.
• PARP inhibitor maintenance therapy is a significant advance, particularly in patients with a confirmed BRCA mutation or other evidence of homologous recombination deficiency, whose tumours are specifically vulnerable to this mechanism. Maintenance after primary chemotherapy substantially improves progression-free survival in appropriately selected patients.
• Bevacizumab, an anti-angiogenic monoclonal antibody, is a further option in primary or maintenance treatment for selected patients according to risk factors and disease characteristics.
• Recurrence occurs in a substantial proportion of patients even after apparently successful primary treatment, given the advanced stage at diagnosis. Management incorporates further chemotherapy, with the regimen informed by the interval since previous platinum-based treatment (platinum sensitivity). It also includes further surgery where appropriate and continued consideration of targeted maintenance therapy.
• Palliative care should be integrated throughout the disease course. It addresses symptom management, including malignant ascites and bowel obstruction from intraperitoneal spread, and psychosocial support. Many women need this approach, given the generally advanced stage and life-limiting nature of the disease.
• Risk reduction for women with confirmed BRCA or other relevant pathogenic mutations includes risk-reducing bilateral salpingo-oophorectomy at an appropriate age, after counselling on its implications, including induced menopause (addressed under primary ovarian insufficiency).
• Women not yet ready for this more definitive step may consider interval opportunistic or risk-reducing salpingectomy alone, reflecting the fallopian tube origin. This is evidence-based care for the higher-risk population, delivered through genetic counselling and a specialist multidisciplinary team.