Cancer of the Ovary

Ovarian cancer is a malignant neoplasm arising from the ovary and is one of the most lethal gynecological cancers. Epithelial tumors account for approximately 90% of all ovarian malignancies. Due to the deep anatomical location of the ovaries and the absence of specific early symptoms, most patients present with advanced disease. Early diagnosis remains challenging, making comprehensive evaluation and timely referral essential for optimal management.

Epidemiology

Ovarian cancer is among the leading causes of death from gynecological malignancies worldwide. Epithelial ovarian cancer is the most common histological subtype. The majority of cases are diagnosed at advanced stages because early-stage disease is often asymptomatic or associated with nonspecific symptoms.

Risk factors

Risk factors for ovarian cancer include:

• Increasing age.

• Family history of ovarian cancer.

• Family history of breast cancer.

• Nulliparity.

• Infertility.

• Early menarche.

• Late menopause.

• Genetic predisposition.

• Previous history of ovarian tumors.

Pathophysiology

Ovarian cancer develops through malignant transformation of ovarian epithelial, germ cell, or stromal tissues, with epithelial tumors accounting for the majority of cases. Malignant cells may spread directly within the peritoneal cavity, invade adjacent pelvic organs, disseminate through lymphatic channels, or metastasize hematogenously.

Peritoneal spread commonly results in:

• Ascites.

• Omental involvement.

• Peritoneal implants.

• Advanced intra-abdominal disease.

Clinical presentation

Early-stage ovarian cancer is frequently asymptomatic or associated with vague symptoms. Clinical manifestations usually become apparent when the disease has reached an advanced stage.

Symptoms

Early disease

• Minimal symptoms.

• No symptoms.

Advanced disease

• Progressive abdominal distension.

• Abdominal pain.

• Sensation of abdominal fullness.

• Symptoms related to ascites.

• Symptoms related to pelvic or abdominal mass.

• Constitutional symptoms in advanced disease.

Clinical signs

• Palpable abdominal or pelvic mass.

• Abdominal distension.

• Ascites.

• Pelvic tenderness.

• Evidence of advanced intra-abdominal disease.

• Signs of metastatic disease in advanced stages.

Differential diagnosis

Conditions that may mimic ovarian cancer include:

• Benign ovarian cysts.

• Endometriosis.

• Uterine fibroids.

• Tubo-ovarian abscess.

• Ectopic pregnancy.

• Pelvic inflammatory disease.

• Ovarian torsion.

• Metastatic tumors involving the ovary.

• Ascites due to chronic liver disease.

• Gastrointestinal malignancies.

Diagnostic criteria

Ovarian cancer should be suspected in women presenting with:

• Persistent abdominal distension.

• Pelvic or abdominal mass.

• Ascites.

• Persistent abdominal pain.

• Unexplained pelvic symptoms.

• Imaging findings suggestive of ovarian malignancy.

Definitive diagnosis requires histological confirmation.

Investigations

Clinical examination

A thorough gynecological examination is mandatory, including:

• Inspection.

• Bimanual examination under anesthesia (EUA).

• Rectovaginal examination.

These examinations help exclude primary disease or extension from other sites, particularly cervical cancer.

Laboratory investigations

• Full blood count (FBC).

• Renal function tests (RFTs).

• Liver function tests (LFTs).

• Cancer antigen 125 (CA 125).

• Carcinoembryonic antigen (CEA).

Imaging investigations

• Chest X-ray (CXR).

• Ultrasound of the abdomen and pelvis.

• Computed tomography (CT) scan of the abdomen and pelvis.

Histopathological investigations

• Histological examination of oophorectomy specimen.

• Histological examination of biopsy obtained during laparotomy.

Cytological investigations

• Ascitic fluid cytology.

• Peritoneal washing cytology.

• Pelvic washing cytology.

Diagnostic staging

Staging is based on surgical findings obtained during laparotomy.

FIGO staging

• Stage IA.

• Stage IB.

• Stage IC.

• Stage IIA.

• Stage IIB.

• Stage IIC.

• Stage IIIA.

• Stage IIIB.

• Stage IIIC.

• Stage IVA.

• Stage IVB.

Management

Management depends on disease stage, histological subtype, resectability, and patient fitness for surgery.

All patients should be evaluated by a gynecologist and a specialized cancer treatment team.

Non-pharmacological treatment

Stage I and Stage II disease

For resectable tumors perform:

• Total abdominal hysterectomy (TAH).

• Bilateral salpingo-oophorectomy (BSO).

• Omentectomy.

Incomplete resection

If complete tumor removal is not possible:

• Maximum cytoreductive (debulking) surgery should be performed.

This should be followed by adjuvant chemotherapy.

Fertility-sparing surgery

Unilateral salpingo-oophorectomy may be considered only for:

• Stage IA tumors.

• Favorable histological subtype.

Stage III disease

• Neoadjuvant chemotherapy.

• Surgery.

• Adjuvant chemotherapy.

Stage IV disease

• Management as for Stage III disease.

• Palliative care may be required according to disease burden and patient condition.

Pharmacological treatment

Adjuvant chemotherapy

Adjuvant chemotherapy is indicated for:

• Stage IC disease.

• Stage II disease.

• High-grade tumors.

• Clear-cell carcinoma of any stage.

Recommended regimen

Carboplatin

• AUC 6 intravenously over 1 hour on Day 1.

AND

Paclitaxel

• 175 mg/m² intravenously over 3 hours on Day 1.

Repeat every 21 days for 6 cycles.

Recurrent disease

Platinum-sensitive disease

Defined as recurrence occurring more than 6 months after the last chemotherapy cycle.

Recommended treatment:

• Carboplatin plus paclitaxel regimen as above.

Platinum-resistant disease

Recommended options include:

• Gemcitabine.

• Bevacizumab.

These may be used:

• As single agents.

• In combination with taxanes.

Where available:

• Liposomal doxorubicin may be used for recurrent disease.

Gemcitabine regimen

Gemcitabine

• 1000 mg/m² intravenously over 30 minutes on Day 1, Day 8, and Day 15.

Repeat every 4 weeks for 6 courses.

Bevacizumab regimen

Bevacizumab

• 15 mg/kg intravenously over 1 hour on Day 1.

Repeat every 3 weeks until disease progression.

Endocrine therapy

Endocrine therapy may be considered in selected patients with recurrent disease.

Tamoxifen plus goserelin regimen

Tamoxifen

• 20 mg orally every 12 hours daily.

AND

Goserelin

• 3.6 mg subcutaneously every 4 weeks.

Or

Goserelin

• 10.8 mg subcutaneously every 12 weeks.

Management according to underlying cause

Early-stage resectable disease

• Surgical management with TAH, BSO, and omentectomy.

• Adjuvant chemotherapy when indicated.

Advanced disease (Stage III and IV)

• Neoadjuvant chemotherapy.

• Cytoreductive surgery.

• Adjuvant chemotherapy.

Recurrent platinum-sensitive disease

• Repeat carboplatin and paclitaxel regimen.

Recurrent platinum-resistant disease

• Gemcitabine.

• Bevacizumab.

• Taxane-containing regimens.

• Liposomal doxorubicin where available.

Recurrent hormone-responsive disease

• Tamoxifen plus goserelin.

Referral

All patients with suspected or confirmed ovarian cancer should be referred urgently to:

• A gynecologist.

• A specialized cancer treatment center.

Referral is required for:

• Diagnostic confirmation.

• Surgical staging.

• Definitive treatment.

• Long-term follow-up.

Complications

• Massive ascites.

• Intestinal obstruction.

• Pleural effusion.

• Peritoneal carcinomatosis.

• Malnutrition.

• Disease recurrence.

• Metastatic disease.

• Treatment-related complications.

• Death.

Prognosis

Prognosis depends on:

• Stage at diagnosis.

• Histological subtype.

• Completeness of surgical tumor removal.

• Response to chemotherapy.

• Presence of recurrent disease.

Early-stage disease has a significantly better prognosis than advanced-stage disease. Most patients presenting with advanced disease require multimodal treatment and long-term surveillance.

Prevention

There are no universally effective screening methods for the general population. Preventive strategies include:

• Awareness of symptoms suggestive of ovarian cancer.

• Early evaluation of persistent abdominal or pelvic symptoms.

• Assessment of women with strong family history of ovarian or breast cancer.

• Timely referral of women with suspected ovarian masses.

Follow-up

Patients should undergo regular follow-up to assess:

• Treatment response.

• Disease recurrence.

• Treatment-related complications.

• Clinical status and quality of life.

Monitoring may include:

• Clinical evaluation.

• CA 125 measurement where appropriate.

• Imaging studies when clinically indicated.