Cancer Care & Research | Dr. Arifur Rahman

Overview

Ovarian cancer arises from abnormal growth of cells in the ovaries, fallopian tubes, or peritoneum. Most cases are **epithelial ovarian cancers (EOC)**—particularly **high-grade serous carcinoma (HGSC)**—while others include **endometrioid**, **clear cell**, **mucinous** subtypes, as well as **germ cell** and **sex cord–stromal** tumors. It is often diagnosed at an advanced stage due to vague, nonspecific symptoms.

Causes & Risk Factors

Known Causes

Malignant transformation results from accumulated genetic and epigenetic alterations influenced by hormonal and inflammatory pathways. Key etiologic contributors include: - **BRCA1/BRCA2** and other homologous recombination repair (HRR) gene defects (germline or somatic) - **Lynch syndrome** (MMR gene mutations) - **Endometriosis** (particularly for clear cell and endometrioid subtypes) - Repeated **ovulatory cycles** (incessant ovulation hypothesis), hormonal factors - Chronic pelvic inflammation

Risk Factors

- Increasing **age** (most common after menopause)

- **Family history** of ovarian, breast, pancreatic, or prostate cancer

- **Inherited mutations**: BRCA1, BRCA2, RAD51C/D, PALB2, BRIP1; Lynch syndrome

- **Endometriosis** (especially for clear cell/endometrioid carcinoma)

- **Nulliparity**, infertility, or **late first pregnancy**

- **Hormone replacement therapy** (long-term, postmenopausal)

- **Obesity** and metabolic factors

- **Smoking** (notably associated with mucinous ovarian carcinoma)

- **Tall height** and possibly **PCOS** (mixed evidence)

- Prior **pelvic radiation** (rare)

Symptoms & Early Signs

Early Warning Signs

Often subtle and easily overlooked: - **Abdominal bloating** or increase in girth - **Pelvic/abdominal pain** or pressure - **Early satiety** or difficulty eating - **Urinary urgency/frequency** - **New-onset constipation** or change in bowel habits - **Unexplained fatigue**

Common Symptoms

- Persistent **bloating** and abdominal distension

- **Pelvic or abdominal pain**

- **Early satiety**, nausea, dyspepsia

- **Urinary urgency/frequency**

- **Back pain**, constipation, or diarrhea

- **Menstrual irregularities** or postmenopausal bleeding (less common)

- **Ascites**, dyspnea (pleural effusion) in advanced disease

- **Unintentional weight loss** and fatigue

Diagnosis

- **Clinical assessment**: Pelvic exam and symptom evaluation - **Transvaginal and pelvic ultrasound** (first-line imaging) - **Serum biomarkers**: **CA-125**, **HE4**; composite algorithms (e.g., **ROMA**) - **CT/MRI** for staging; **PET-CT** in selected cases - **Diagnostic laparoscopy/laparotomy** for histologic confirmation and surgical staging/cytoreduction - **Cytology** of ascites/pleural fluid when present - **Pathology & molecular profiling**: Histotype, **BRCA1/2** (germline and somatic), **HRD** status, **MMR/MSI**; broader NGS panels to guide targeted therapy

Staging Information

FIGO **staging (I–IV)** for ovarian, fallopian tube, and primary peritoneal cancers: - **Stage I**: Confined to one/both ovaries or fallopian tubes - **Stage II**: Pelvic extension (uterus/tubes or other pelvic tissues) - **Stage III**: Peritoneal metastasis outside pelvis and/or regional lymph nodes - **Stage IV**: Distant metastasis (parenchymal liver/spleen, pleural effusion with positive cytology)

Treatment Information

Treatment Overview

Management is multidisciplinary; intent is **curative** for localized disease and **cytoreductive** for advanced disease. - **Surgery**: Comprehensive surgical staging (for early) or **cytoreductive debulking** (for advanced). Goal is **no gross residual** disease. - **Chemotherapy**: **Platinum–taxane** doublet (carboplatin + paclitaxel) as standard first-line; **neoadjuvant chemotherapy** with **interval debulking** for selected advanced cases. - **Maintenance therapy**: - **PARP inhibitors** (**olaparib**, **niraparib**, **rucaparib**) for **BRCA-mutated** and/or **HRD-positive** disease after response to platinum. - **Bevacizumab** (anti-VEGF) ± continuation as maintenance in selected patients. - **Targeted/biologic therapy**: PARP inhibitors; **bevacizumab**. (CLDN6/other targeted agents under study.) - **Immunotherapy**: Limited role; consider for **MSI-H/dMMR** or in trials. - **Recurrent disease**: - **Platinum-sensitive**: platinum-based combinations ± bevacizumab; consider PARP maintenance if not previously used. - **Platinum-resistant**: non-platinum agents (liposomal doxorubicin, weekly paclitaxel, topotecan, gemcitabine) ± bevacizumab; clinical trials. - **Radiation therapy**: Palliative for symptomatic metastases. - **Supportive care**: Management of ascites (paracentesis/IPC), thromboembolism prophylaxis, nutrition, pain control.

5-Year Survival Rate

N/A

Available Treatments

0

Treatment Options

Prognosis & Outlook

Prognosis depends on stage, residual disease after surgery, histotype, and molecular profile (BRCA/HRD). - **Early-stage** disease has excellent outcomes when completely staged and treated. - **Advanced-stage** disease is often chronic/relapsing; survival has improved with **PARP inhibitors** and optimized cytoreduction. - **BRCA-mutated/HRD-positive** tumors generally have better response to platinum and PARP inhibitors.

Prevention & Early Detection

- **Oral contraceptives** (³5 years) reduce risk by ~30–50%. - **Risk-reducing salpingo-oophorectomy (RRSO)** after childbearing for **BRCA1/2** carriers (typically by age 35–45 for BRCA1; 40–50 for BRCA2). - **Opportunistic salpingectomy** during benign gynecologic surgery may reduce risk. - **Breastfeeding** and **parity** lower risk; avoid unnecessary long-term **HRT**. - **Manage endometriosis** appropriately. - **Routine screening is not recommended** for average-risk women (CA-125/TVUS lack mortality benefit); high-risk women may undergo individualized surveillance while planning RRSO. - **Genetic counseling/testing** for women with suggestive personal/family history.

Support & Resources

- **Healthcare team**: Gynecologic oncologists, medical oncologists, oncology nurses, palliative care, genetic counselors, dietitians. - **Patient organizations**: **Ovarian Cancer Research Alliance (OCRA)**, **National Ovarian Cancer Coalition (NOCC)**, **Target Ovarian Cancer** (UK), **Macmillan Cancer Support**. - **Hereditary cancer support**: **FORCE (Facing Our Risk of Cancer Empowered)** for BRCA/Lynch. - **Online communities**: CancerCare, Smart Patients, local hospital groups. - **Survivorship & rehab**: Management of fatigue, neuropathy, sexual health, fertility preservation (for younger patients), psychosocial and financial counseling.

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Ovarian Cancer: Comprehensive Overview