Gynaecology

Ovarian Cancer

Table of Contents

Introduction

Ovarian cancer is the second most common gynecological malignancy and the major cause of death from gynecological cancers.
When detected in its early stages, ovarian cancer has an excellent prognosis.
However, the poor overall survival rates reflect the advanced stage at which most women present.


Classification

  1. Epithelial ovarian tumors (80%)

  2. Sex cord stromal tumors (10%)

  3. Germ cell tumors (10%)

  4. Metastatic tumors (including Krukenberg tumors)

Epithelial Ovarian Tumors

Epithelial tumors of the ovary may be benign, malignant, or borderline.
Approximately 10% of epithelial tumors are classified as borderline ovarian tumors (BOTs).

Borderline ovarian tumors (BOTs) are:

  • Well differentiated, with some malignant features (nuclear pleomorphism and cellular atypia),

  • But they do not invade the basement membrane.

These tumors may spread to other abdominopelvic structures such as the peritoneum and omentum,
but they rarely recur after initial surgery.

It is estimated that 10–15% of women with epithelial ovarian cancer have a hereditary predisposition.
Women with BRCA1, BRCA2 mutations or Lynch syndrome have an increased lifetime risk of developing epithelial ovarian cancer.


Sex Cord Stromal Tumors

These tumors account for approximately 10% of ovarian tumors,
but represent nearly 90% of all functional (hormone-producing) tumors.

They are generally low malignant potential tumors with a good long-term prognosis.
Some morbidity may occur due to estrogen or androgen production, which can result in:

  • Precocious puberty

  • Abnormal menstrual bleeding

  • Increased risk of endometrial cancer

The peak incidence occurs around the menopausal age,
although juvenile granulosa cell tumors may occur in girls under 10 years, causing precocious puberty.

A significant number of these tumors present with hormonal manifestations, including:

  • Irregular menstrual bleeding

  • Postmenopausal bleeding

  • Precocious puberty in young girls


Germ Cell Tumors

Malignant germ cell tumors occur mainly in young women and constitute about 10% of ovarian tumors.
They are derived from primordial germ cells of the ovary and may contain any cell type.

The management of germ cell tumors primarily focuses on fertility-preserving surgery and chemotherapy.

The most common presenting symptom is a pelvic mass.
About 10% of cases present acutely with torsion or hemorrhage,
and some occur during pregnancy due to their age distribution.

Approximately 70% of germ cell tumors are Stage I at presentation.
Spread occurs via lymphatic or blood-borne routes.

Subtypes of Germ Cell Tumors
  • Dysgerminomas account for 50% of all germ cell tumors.

    • Bilateral in 20% of cases.

    • May secrete human chorionic gonadotrophin (hCG) occasionally.

  • Endodermal sinus (yolk sac) tumors are the second most common,
    accounting for 15% of germ cell tumors.

    • Rarely bilateral.

    • Secrete α-fetoprotein (AFP).

    • Present as large solid masses often causing acute symptoms such as torsion or rupture.

    • Spread (usually to lungs) is a late event.

  • Immature teratomas constitute 15–20% of malignant germ cell tumors and about 1% of all teratomas.

    • About one-third secrete AFP.

    • Occasionally, malignant transformation occurs in a mature teratoma—most commonly to squamous cell carcinoma.


Risk Factors for Ovarian Cancer

  • Genetic predisposition (BRCA1, BRCA2, Lynch syndrome)

  • Nulliparity

  • Obesity

  • Cigarette smoking (especially for mucinous tumors)

  • Intrauterine device (IUD) use

  • Endometriosis


Diagnosis and Investigations

When ovarian cancer is suspected, a Transvaginal Ultrasound Scan (TVUSS) is the initial imaging test of choice
to assess pelvic pathology.

A pelvic mass is characterized by:

  • Size and consistency

  • Presence of solid elements

  • Bilaterality

  • Ascites

  • Extra-ovarian disease (peritoneal thickening, omental deposits)


Tumor Markers
  • CA125 is a non-specific tumor marker elevated in >80% of epithelial ovarian cancers.

    • However, it is raised in only ~50% of early-stage cancers.

    • It can also be elevated in benign conditions such as:

      • Pregnancy

      • Endometriosis

      • Alcoholic liver disease


Risk of Malignancy Index (RMI)

The RMI combines:

  • Menopausal status

  • Pelvic ultrasound features

  • CA125 level

It is used to classify pelvic masses into low, intermediate, or high risk of malignancy.


Further Imaging

If pelvic pathology indicates intermediate or high risk, further imaging includes:

  • Computed Tomography (CT) scan — to assess extra-pelvic disease and staging

  • Magnetic Resonance Imaging (MRI) — to define tissue planes and operability


Additional Preoperative Investigations
  • Chest X-ray

  • Electrocardiogram (ECG)

  • Full blood count (FBC)

  • Urea and electrolytes (U&E)

  • Liver function tests (LFTs)

If the patient presents with gross ascites or pleural effusion, perform:

  • Paracentesis or pleural aspiration for symptom relief and/or diagnosis.

    • A sample of the fluid should be sent for cytological examination.

If the diagnosis remains uncertain or primary chemotherapy is being considered (for advanced disease or unfit patients),
a biopsy is needed before treatment — performed either laparoscopically or under ultrasound/CT guidance.
The omentum is usually the preferred biopsy site.


Management

Surgery
  • Vertical midline incision is used to access all abdominal regions.

  • Ascitic fluid or peritoneal washings are collected for cytology.

  • Standard procedure includes:

    • Total abdominal hysterectomy (TAH)

    • Bilateral salpingo-oophorectomy (BSO)

    • Omentectomy

Further debulking may be required, including:

  • Bowel resection

  • Peritoneal stripping

  • Splenectomy

These aim to achieve complete tumor removal.
Lymph node resection is important, especially in early-stage disease, as studies show occult metastasis may occur.


Conservative Surgery

In young patients with early-stage epithelial ovarian cancer who wish to preserve fertility,
conservative surgery can be performed:

  • Unilateral salpingo-oophorectomy

  • Omentectomy

  • Peritoneal biopsies

  • Pelvic and para-aortic lymph node dissection

  • Endometrial sampling to exclude a synchronous endometrial tumor


Chemotherapy

Platinum compounds are the most effective agents in treating ovarian cancer.
They act by cross-linking DNA strands, thereby arresting cell replication.

Main Agents

  • Carboplatin (preferred due to lower renal toxicity and less nausea)

  • Cisplatin (equally effective but more toxic)


Uses of Chemotherapy
  • Primary treatment

  • Adjuvant therapy after surgery

  • Recurrent disease

Chemotherapy can:

  • Prolong clinical remission

  • Improve overall survival

  • Provide palliation in advanced stages

The first-line combination is usually:

  • Platinum compound (Carboplatin or Cisplatin)

    • Paclitaxel


Paclitaxel

Paclitaxel works by damaging microtubules, disrupting cell division.
A known side effect is total hair loss (alopecia), regardless of dose.


Bevacizumab

Bevacizumab is a monoclonal antibody against Vascular Endothelial Growth Factor (VEGF).
It inhibits angiogenesis, the formation of new blood vessels that feed the tumor.

When combined with carboplatin and paclitaxel,
Bevacizumab has been shown to:

  • Improve recurrence-free survival

  • Improve overall survival in advanced ovarian cancer

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