Ovarian Cancer

Introduction

Ovarian cancer is the most lethal gynaecological malignancy, not because it is the most common, but because it is so often diagnosed late. Symptoms are typically vague, non-specific, and easily attributed to more common benign conditions (irritable bowel syndrome, menopause, simple bloating), earning it the informal label of the 'silent killer' - though in reality symptoms are often present for some time before diagnosis, just not recognised as significant.¹

Around 90% of ovarian cancers are epithelial in origin, arising from the surface epithelium of the ovary or, as increasingly understood for high-grade serous carcinoma, from the fimbrial end of the fallopian tube. The remaining minority are germ cell tumours and sex cord-stromal tumours, which behave very differently and are discussed separately below.

Classification and histology

Risk factors

The dominant model for epithelial ovarian cancer risk relates to the total number of ovulatory cycles across a lifetime - more ovulation means more repeated epithelial disruption and repair at the ovarian surface, increasing the chance of a malignant mutation arising.²

Factors that increase risk (more lifetime ovulation)

• Nulliparity
• Early menarche and late menopause
• Increasing age
• Obesity
• Hormone replacement therapy (modest increased risk)
• Smoking (specifically increases risk of mucinous subtype)

Genetic risk

• BRCA1 mutation: lifetime ovarian cancer risk of roughly 40-60%
• BRCA2 mutation: lifetime risk of roughly 10-20%
• Lynch syndrome (HNPCC): increased risk of ovarian cancer alongside colorectal and endometrial cancer
• A strong family history of breast or ovarian cancer should prompt referral for genetic counselling and testing

Factors that reduce risk (less lifetime ovulation)

• Combined oral contraceptive pill use (a well-established protective effect, increasing with duration of use)
• Multiparity and breastfeeding
• Risk-reducing bilateral salpingo-oophorectomy in known mutation carriers, typically once childbearing is complete

Clinical features

Symptoms are frequently vague, persistent, and easily mistaken for other, more common conditions - which is precisely why ovarian cancer so often presents late.³

• Persistent abdominal bloating (not intermittent)
• Early satiety or loss of appetite
• Pelvic or abdominal pain
• Increased urinary urgency and/or frequency
• Change in bowel habit
• Unexplained weight loss or fatigue in more advanced disease
• A palpable abdominal or pelvic mass, or ascites, in more advanced disease

Investigations

The investigation pathway starts in primary care and escalates based on results, mirroring the approach used for any suspicious ovarian mass (see the ovarian cysts article for full detail on ultrasound features and the RMI calculation).⁴

CA-125

First-line blood test in primary care for a woman with suggestive symptoms. If raised (typically ≥35 units/mL, though local thresholds vary), arrange a pelvic (and abdominal) ultrasound. CA-125 is non-specific - also raised by endometriosis, fibroids, pregnancy, menstruation, and benign conditions like pelvic infection or liver disease - so it is interpreted in context, not in isolation.

Ultrasound and RMI

Pelvic ultrasound assesses for an ovarian mass and its features. The Risk of Malignancy Index (RMI), combining ultrasound score, menopausal status and CA-125 level, stratifies risk and determines whether referral to a specialist gynaecological oncology multidisciplinary team (MDT) is needed - see the ovarian cysts article for the full RMI calculation.

Further staging investigations

CT chest/abdomen/pelvis assesses the extent of disease (peritoneal spread, ascites, lymphadenopathy, distant metastasis) once malignancy is suspected or confirmed, to guide surgical and oncological planning. In selected younger women with a complex mass, additional tumour markers (AFP, hCG, LDH) are checked to screen for a germ cell tumour, and inhibin B may be checked if a granulosa cell tumour is suspected.

Staging

Ovarian cancer uses surgical-pathological FIGO staging, determined at the time of surgery (unlike cervical cancer, which is staged clinically/radiologically) - staging laparotomy with full surgical exploration is itself part of both diagnosis and treatment.⁵

Because early symptoms are so non-specific, the majority of epithelial ovarian cancers are diagnosed at stage III or IV, which is the central reason for its comparatively poor overall survival relative to other gynaecological cancers.

Management

Management of epithelial ovarian cancer combines cytoreductive surgery with platinum-based chemotherapy, planned by a specialist gynaecological oncology MDT.¹

Surgery

Cytoreductive ('debulking') surgery aims to remove all visible tumour - typically total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and resection of any other visible peritoneal disease. The completeness of debulking (achieving no visible residual disease) is one of the strongest independent predictors of survival, which is why surgical expertise and thorough resection matter so much in this cancer specifically.

Chemotherapy

Platinum-based chemotherapy (typically carboplatin, often combined with paclitaxel) is given adjuvantly after surgery for most stages beyond very early disease, and can be given neoadjuvantly (before surgery) in advanced or extensively disseminated disease to shrink tumour burden and improve the chance of complete surgical debulking.

Maintenance and targeted therapy

PARP inhibitors (e.g. olaparib) are used as maintenance therapy in some women, particularly those with a BRCA mutation, following response to platinum-based chemotherapy, reflecting increasing use of molecular profiling to guide treatment.

Non-epithelial ovarian tumours

Germ cell tumours

Typically affect children and young women. Unlike epithelial ovarian cancer, they are often highly chemosensitive, and even advanced disease can achieve good long-term survival with platinum-based chemotherapy - a notably different prognostic picture that is worth contrasting explicitly with epithelial disease.

Sex cord-stromal tumours

Granulosa cell tumours can secrete oestrogen, presenting with abnormal uterine bleeding, precocious puberty in children, or postmenopausal bleeding, and can be associated with endometrial hyperplasia or cancer from the resulting unopposed oestrogen. Sertoli-Leydig cell tumours can secrete androgens, causing virilisation (hirsutism, deepening voice, clitoromegaly).

Complications

• Bowel obstruction from peritoneal disease (a common cause of morbidity in advanced disease)
• Ascites requiring drainage
• Pleural effusion
• Venous thromboembolism (ovarian cancer carries a particularly high VTE risk among cancers)
• Treatment-related complications: surgical morbidity, chemotherapy toxicity (myelosuppression, neuropathy)
• Psychological impact of diagnosis, often at an advanced stage

Prognosis

Prognosis is strongly stage-dependent, and because the majority of epithelial ovarian cancers present at stage III or IV, overall survival is worse than for endometrial or cervical cancer despite being a less common disease. Completeness of surgical debulking and response to platinum-based chemotherapy are the strongest modifiable determinants of outcome. Non-epithelial tumours (germ cell, in particular) carry a much better prognosis than epithelial disease at an equivalent stage, underscoring why histological subtype - not stage alone - shapes the prognostic conversation with a patient.