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Ovarian Cancer for ABIM

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Ovarian Cancer for the American Board of Internal Medicine Exam
Ovarian Cancer
  • Epidemiology:
    • Ovarian cancer is the second most common gynecologic malignancy but has the highest mortality rate among them due to late-stage presentation.
    • Risk Factors:
    • Age (most common in postmenopausal women, typically aged 50–70).
    • Family history of ovarian, breast, or colorectal cancer.
    • BRCA1 or BRCA2 mutations increase lifetime risk significantly.
    • Lynch syndrome (hereditary nonpolyposis colorectal cancer) also raises the risk.
    • Factors that increase lifetime ovulatory cycles, such as nulliparity, early menarche, and late menopause.
    • Protective Factors:
    • Oral contraceptive use, pregnancy, and breastfeeding, which reduce the number of ovulatory cycles.
Types of Ovarian Cancer
  • Epithelial Tumors:
    • Comprise 90% of ovarian cancers and are classified based on cell type:
    • Serous Carcinomas: The most common epithelial subtype, often high-grade and aggressive.
    • Mucinous Carcinomas: Less common and may grow large.
    • Endometrioid and Clear Cell Carcinomas: Often associated with endometriosis.
    • Low-Grade vs. High-Grade Serous Carcinomas: High-grade tumors are more common and aggressive, frequently presenting at advanced stages.
  • Germ Cell Tumors:
    • Arise from primordial germ cells, often affecting younger women (typically under 30).
    • Subtypes include dysgerminomas, yolk sac tumors, choriocarcinomas, and immature teratomas.
    • Generally have a good prognosis with treatment and are often highly chemosensitive.
  • Sex Cord-Stromal Tumors:
    • Arise from ovarian stromal cells, producing steroid hormones, which can lead to symptoms from hormone secretion.
    • Granulosa Cell Tumors: Produce estrogen, causing symptoms such as abnormal bleeding or precocious puberty in children.
    • Sertoli-Leydig Cell Tumors: Produce androgens, which may cause virilization in women.
Clinical Presentation
  • Symptoms:
    • Ovarian cancer is often asymptomatic in early stages, with vague or nonspecific symptoms appearing later.
    • Common symptoms include:
    • Abdominal bloating or distension.
    • Early satiety and difficulty eating.
    • Pelvic or abdominal pain.
    • Urinary frequency or urgency.
    • Advanced Disease: May present with ascites, cachexia, bowel obstruction, or pleural effusion.
  • Physical Exam Findings:
    • Abdominal or Pelvic Mass: May be palpated on examination.
    • Ascites: Fluid accumulation in the abdomen, often present in advanced disease.
    • Pleural Effusion: Particularly on the right side, may be detected if metastasis has occurred.
Diagnosis
  • Imaging:
    • Pelvic Ultrasound: First-line imaging for an adnexal mass.
    • Malignant features include solid components, thick septations, papillary projections, irregular borders, and ascites.
    • CT Scan of the Abdomen and Pelvis: Used for staging and evaluating metastasis.
    • MRI: Sometimes used for further characterization of indeterminate masses.
  • Laboratory Testing:
    • CA-125:
    • A serum tumor marker often elevated in epithelial ovarian cancers, particularly serous carcinoma.
    • Not specific for ovarian cancer; levels can be elevated in benign conditions like endometriosis and pelvic inflammatory disease.
    • Useful for monitoring response to treatment and disease recurrence in patients with confirmed ovarian cancer.
    • Other Tumor Markers:
    • AFP, hCG, and LDH: Elevated in some germ cell tumors (e.g., yolk sac tumors, choriocarcinoma, and dysgerminomas).
    • Inhibin and Estradiol: Can be elevated in granulosa cell tumors due to hormone secretion.
  • Histopathology:
    • Required for definitive diagnosis.
    • Obtained through surgical exploration, which may involve laparotomy or laparoscopy for biopsy and staging.
Staging and Prognosis
  • FIGO Staging (International Federation of Gynecology and Obstetrics):
    • Stage I: Confined to the ovaries.
    • Stage II: Extends to pelvic organs (e.g., uterus, fallopian tubes).
    • Stage III: Spread to abdominal organs or lymph nodes.
    • Stage IV: Distant metastasis (e.g., pleural effusion with positive cytology, liver or spleen parenchymal involvement).
    • Prognosis:
    • Five-year survival rates are high for early-stage ovarian cancer (stages I and II), but most patients present with advanced disease (stage III or IV), where prognosis is poor.
Treatment
  • Surgical Treatment:
    • Debulking Surgery: Standard approach for advanced epithelial ovarian cancer, involving removal of as much tumor as possible.
    • Involves hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and often lymph node dissection.
    • Fertility-Sparing Surgery: May be considered in young women with early-stage disease or specific germ cell tumors.
  • Chemotherapy:
    • Platinum-Based Chemotherapy: Mainstay for epithelial ovarian cancers, typically using carboplatin and paclitaxel.
    • Neoadjuvant Chemotherapy: Given before surgery in patients who are not good candidates for primary debulking surgery.
    • Germ Cell Tumors: Highly sensitive to chemotherapy, with BEP regimen (bleomycin, etoposide, and cisplatin) as standard.
  • Targeted Therapy:
    • PARP Inhibitors: Used in BRCA-mutated and some homologous recombination-deficient ovarian cancers.
    • Drugs like olaparib inhibit DNA repair in cancer cells, prolonging progression-free survival.
    • Anti-Angiogenic Therapy: Bevacizumab, an anti-VEGF antibody, is sometimes used in advanced ovarian cancer to inhibit tumor blood vessel growth.
  • Hormonal Therapy:
    • May be used in selected patients with low-grade serous carcinoma or sex cord-stromal tumors that produce hormones.
  • Radiation Therapy:
    • Rarely used in ovarian cancer due to limited efficacy in advanced disease; however, it may be considered for localized symptom control in selected cases.
Surveillance
  • Follow-Up:
    • CA-125: Monitored periodically in patients with confirmed epithelial ovarian cancer for early detection of recurrence.
    • Imaging: CT scans or ultrasounds may be done based on symptoms or elevated tumor markers.
  • Recurrence Management:
    • Recurrent disease is often treated with additional chemotherapy or PARP inhibitors for patients with BRCA mutations or homologous recombination deficiency.
Key Points
  • Ovarian Cancer is highly fatal due to late-stage presentation, with epithelial tumors being the most common type.
  • Risk Factors include family history, BRCA1/BRCA2 mutations, and factors that increase ovulatory cycles, while protective factors include oral contraceptive use and pregnancy.
  • Diagnosis relies on imaging (pelvic ultrasound, CT scan) and serum tumor markers (CA-125), with histopathology confirming diagnosis.
  • Staging follows the FIGO system, and prognosis depends on the stage at diagnosis, with early-stage disease having a significantly better prognosis.
  • Treatment involves debulking surgery and platinum-based chemotherapy for epithelial tumors, while targeted therapies (PARP inhibitors) and anti-angiogenics (bevacizumab) are also used in advanced disease.
  • Surveillance includes monitoring CA-125 levels and imaging in symptomatic or elevated-marker cases to detect recurrence.

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