Ovarian Cancer

What is Ovarian Cancer?

Ovarian cancer develops when cells in or near the ovaries grow abnormally and form a tumor. The ovaries are two small, almond-shaped organs located on either side of the uterus. They produce eggs (ova) and female hormones estrogen and progesterone.

The main challenge with ovarian cancer is that it often goes undetected until it has spread beyond the ovaries to the pelvis and abdomen. At this later stage, it becomes more difficult to treat and is more likely to be fatal. Early-stage ovarian cancer, confined to the ovary, is more successfully treated.

Types of Ovarian Cancer

Ovarian cancer is classified based on the type of cell where it begins:

Epithelial Ovarian Cancer (90%)

Begins in the thin tissue covering the outside of the ovaries or in the fallopian tubes. Subtypes include:

• High-grade serous (70%): Most common and aggressive, often diagnosed at advanced stages. Frequently associated with BRCA mutations and responds well to platinum chemotherapy.
• Endometrioid (10%): Often associated with endometriosis and endometrial cancer. Usually diagnosed at earlier stages.
• Clear cell (10%): More common in Asian populations. Less responsive to standard chemotherapy.
• Mucinous (3%): Produces mucin. Often larger tumors at diagnosis.
• Low-grade serous (5%): Grows more slowly than high-grade. Different treatment approach.

Germ Cell Tumors (5%)

Begin in the egg-producing cells. More common in younger women and teenagers. Generally have excellent prognosis with treatment. Types include dysgerminoma, immature teratoma, and yolk sac tumors.

Stromal Tumors (5%)

Develop in the connective tissue cells that produce hormones. Often diagnosed at earlier stages because they can produce estrogen or testosterone, causing noticeable symptoms. Include granulosa cell tumors and Sertoli-Leydig cell tumors.

Symptoms and Warning Signs

Ovarian cancer symptoms are often vague and easily attributed to other conditions, which contributes to late diagnosis. However, women with ovarian cancer are more likely to consistently experience the following:

Primary Symptoms

• Bloating or swelling of the abdomen - Persistent, not related to eating
• Pelvic or abdominal pain - Can be dull or sharp
• Early satiety - Feeling full quickly when eating
• Urinary symptoms - Urgency or frequency

Additional Symptoms

• Fatigue
• Upset stomach or heartburn
• Back pain
• Constipation
• Changes in menstrual cycle
• Pain during intercourse
• Unexplained weight loss or gain

Causes and Risk Factors

The exact cause of ovarian cancer is unclear, but certain factors increase risk:

Genetic Risk Factors

• BRCA1 or BRCA2 mutations: Inherited gene mutations significantly increase risk (35-70% for BRCA1, 10-30% for BRCA2). Also increase breast cancer risk.
• Lynch syndrome: Hereditary condition that increases colorectal and ovarian cancer risk (10-12% lifetime risk).
• Family history: Having a first-degree relative (mother, sister, daughter) with ovarian cancer doubles risk.

Reproductive and Hormonal Factors

• Nulliparity: Never having been pregnant increases risk
• Age at menopause: Late menopause (after age 55) increases risk
• Early menstruation: Starting periods before age 12
• Hormone therapy: Long-term use of estrogen-only HRT (after menopause) may increase risk

Other Risk Factors

• Age: Risk increases with age, especially after 50
• Endometriosis: Increases risk of clear cell and endometrioid types
• Obesity: BMI over 30 associated with increased risk
• Smoking: Increases risk of mucinous ovarian cancer

Protective Factors

The following factors are associated with decreased risk:

• Pregnancy and breastfeeding: Each full-term pregnancy reduces risk by ~10%
• Oral contraceptives: Use for 5+ years reduces risk by ~50%
• Tubal ligation: Tying fallopian tubes reduces risk
• Hysterectomy: Removal of uterus (with ovaries intact) reduces risk

Diagnosis and Screening

Diagnostic Tests

If ovarian cancer is suspected based on symptoms or imaging, the following tests may be used:

1. Pelvic Examination

Your doctor manually checks the size, shape, and consistency of your ovaries and uterus. However, it's difficult to feel early-stage ovarian tumors during a pelvic exam.

2. Imaging Tests

• Transvaginal ultrasound: Probe inserted into the vagina to create images of the ovaries. Can identify masses but cannot confirm cancer.
• CT or MRI: Used to determine extent of disease and plan surgery.
• PET scan: May be used to assess spread of disease.

3. CA-125 Blood Test

CA-125 is a protein often elevated in ovarian cancer. However:

• Not all ovarian cancers produce CA-125 (especially mucinous and clear cell types)
• CA-125 can be elevated in benign conditions (endometriosis, fibroids, pelvic inflammatory disease)
• More useful for monitoring treatment response than initial diagnosis
• Normal CA-125 is <35 U/mL, but levels can vary

4. Biopsy and Surgery

The only definitive way to diagnose ovarian cancer is through biopsy. Unlike some cancers, biopsy is usually done during surgery to remove the tumor, not beforehand, to avoid potential spread of cancer cells.

Screening Limitations

There is no effective screening test for ovarian cancer in average-risk women. Neither CA-125 testing nor transvaginal ultrasound has been shown to reduce deaths from ovarian cancer when used for routine screening. These tests have high false-positive rates and can lead to unnecessary surgeries.

Staging

Ovarian cancer is staged using the FIGO (International Federation of Gynecology and Obstetrics) system, which describes how far the cancer has spread:

Important note: About 60% of ovarian cancers are diagnosed at Stage III or IV, when the cancer has already spread beyond the ovaries. This is why early detection is so challenging and crucial.

Treatment Options

Treatment depends on the stage, type, and grade of cancer, as well as your overall health and preferences. Most patients receive a combination of surgery and chemotherapy.

Surgery

Surgery is the primary treatment for most ovarian cancers. The goals are:

Staging Surgery (Early-Stage)

For apparent early-stage cancer, surgery includes:

• Removal of ovaries and fallopian tubes (bilateral salpingo-oophorectomy)
• Removal of uterus (hysterectomy) - usually recommended
• Removal of omentum (fatty tissue in abdomen)
• Lymph node sampling
• Peritoneal biopsies and fluid sampling

Fertility-sparing surgery: In select cases of Stage IA disease in young women who want to preserve fertility, only the affected ovary and fallopian tube may be removed.

Cytoreductive (Debulking) Surgery (Advanced-Stage)

The goal is to remove as much cancer as possible. Studies show that the amount of remaining cancer (residual disease) after surgery is the strongest predictor of survival:

• Optimal debulking: No visible tumor remaining (R0) or <1 cm residual tumor
• Suboptimal debulking: >1 cm residual tumor

Surgery may involve removing multiple organs (bowel, spleen, diaphragm portions) to achieve complete tumor removal. This extensive surgery is best performed by a gynecologic oncologist.

Interval Debulking Surgery

If initial tumor burden is too extensive, patients may receive 3-4 cycles of chemotherapy first (neoadjuvant chemotherapy) to shrink tumors, followed by surgery, then additional chemotherapy.

Chemotherapy

Most ovarian cancer patients receive chemotherapy after surgery (adjuvant chemotherapy) to kill any remaining cancer cells.

Standard Regimen

The standard chemotherapy for epithelial ovarian cancer is:

• Carboplatin or cisplatin (platinum agent)
• Plus paclitaxel (taxane)
• Given intravenously every 3 weeks for 6 cycles

Intraperitoneal (IP) Chemotherapy

For some patients with optimally debulked Stage III disease, chemotherapy can be delivered directly into the abdominal cavity. This approach has shown survival benefits but has more side effects and is not suitable for everyone.

Common Side Effects

• Neutropenia (low white blood cells)
• Peripheral neuropathy (nerve damage from taxanes)
• Nausea and vomiting
• Fatigue
• Hair loss

Targeted Therapy

PARP Inhibitors

PARP inhibitors are oral medications that prevent cancer cells from repairing DNA damage. They are particularly effective in cancers with BRCA mutations or homologous recombination deficiency (HRD):

• Olaparib (Lynparza): First-line maintenance for BRCA-mutated or HRD-positive advanced ovarian cancer
• Niraparib (Zejula): First-line maintenance regardless of biomarker status
• Rucaparib (Rubraca): Maintenance therapy after response to platinum chemotherapy

PARP inhibitors have significantly improved progression-free survival in the maintenance setting. Common side effects include fatigue, nausea, anemia, and low blood counts.

Bevacizumab (Avastin)

An anti-angiogenesis drug that blocks blood vessel growth to tumors. Used in combination with chemotherapy and as maintenance therapy for advanced ovarian cancer. Can improve progression-free survival but not overall survival. Requires monitoring for high blood pressure, bleeding, and bowel perforation.

Radiation Therapy

Rarely used for ovarian cancer but may be recommended for:

• Palliative treatment of localized recurrence
• Pain control from metastases

Treatment of Recurrent Disease

Unfortunately, about 70% of advanced ovarian cancers recur. Treatment depends on:

Platinum-Sensitive Recurrence (>6 months after last platinum)

• Platinum-based combination chemotherapy
• May consider secondary cytoreductive surgery in select cases
• PARP inhibitor maintenance if platinum-sensitive

Platinum-Resistant Recurrence (<6 months after last platinum)

• Non-platinum single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin, topotecan, gemcitabine)
• Consider clinical trials
• Focus on symptom control and quality of life

Prognosis and Survival

Prognosis for ovarian cancer depends heavily on the stage at diagnosis:

Survival by Stage

• Stage I: 92% 5-year survival
• Stage II: 75% 5-year survival
• Stage III: 45% 5-year survival
• Stage IV: 30% 5-year survival
• Overall (all stages): ~50% 5-year survival

Prognostic Factors

Factors that influence outcomes include:

Favorable Factors

• Early-stage disease at diagnosis
• Low-grade tumors
• Complete surgical removal of visible tumor (R0 resection)
• Younger age
• Good performance status
• Endometrioid or mucinous histology (compared to high-grade serous)

Unfavorable Factors

• Advanced-stage disease
• High-grade tumors
• Large residual disease after surgery (>1 cm)
• Clear cell histology (less responsive to chemotherapy)
• Ascites (fluid in abdomen)
• Platinum-resistant recurrence

Prevention and Early Detection

While there's no guaranteed way to prevent ovarian cancer, certain strategies can reduce risk:

Risk Reduction Strategies

1. Oral Contraceptives

Birth control pills reduce ovarian cancer risk by about 50% when used for 5+ years. The protective effect lasts for decades after stopping. Discuss benefits and risks with your doctor.

2. Pregnancy and Breastfeeding

Each full-term pregnancy and period of breastfeeding reduces ovarian cancer risk by giving the ovaries a break from ovulation.

3. Risk-Reducing Surgery

For women at high risk (BRCA mutations, Lynch syndrome, strong family history):

• Bilateral salpingo-oophorectomy (BSO): Removal of both ovaries and fallopian tubes reduces risk by 80-90%
• Typically recommended after age 35-40 and completion of childbearing
• Also reduces breast cancer risk in BRCA carriers
• Causes surgical menopause if done before natural menopause

4. Tubal Ligation

"Tying the tubes" for birth control reduces ovarian cancer risk by about 30%. The mechanism is not fully understood but may involve blocking inflammatory substances from reaching the ovaries.

5. Genetic Counseling and Testing

If you have a family history of breast or ovarian cancer, consider genetic counseling to assess your risk and discuss testing for BRCA and other hereditary cancer genes.

Know Your Risk

Talk to your healthcare provider about:

• Your family history of breast and ovarian cancer
• Your reproductive history
• Whether genetic testing is appropriate for you
• Risk-reduction options based on your individual situation

Living with Ovarian Cancer

An ovarian cancer diagnosis brings many challenges, but you don't have to face them alone.

Coping with Treatment Side Effects

• Neuropathy: See peripheral neuropathy for management strategies
• Fatigue: Balance rest and activity; see cancer-related fatigue
• Menopausal symptoms: If ovaries are removed, you'll experience surgical menopause. Discuss management options with your doctor
• Emotional health: Anxiety and depression are common. Consider counseling or support groups

Sexuality and Intimacy

Treatment can affect sexual function through:

• Surgical menopause causing vaginal dryness
• Emotional impacts of diagnosis and treatment
• Physical changes from surgery
• Neuropathy affecting sensation

Communicate openly with your partner and healthcare team. Options include vaginal moisturizers, lubricants, and counseling.

Follow-Up Care

After treatment, you'll need regular monitoring:

• Physical exams: Every 2-4 months for 2 years, then every 6 months
• CA-125 testing: If it was elevated at diagnosis, monitored regularly
• CT scans: As clinically indicated if symptoms arise
• PET scans: May be used to evaluate suspected recurrence

Support Resources

• Ovarian Cancer Research Alliance (OCRA): ocrahope.org
• Foundation for Women's Cancer: foundationforwomenscancer.org
• National Ovarian Cancer Coalition: ovarian.org
• FORCE (Hereditary Cancer): facingourrisk.org

Frequently Asked Questions