Gynecological Cancers

Epithelial Ovarian Cancer

Ovarian cancer includes fallopian tube and primary peritoneal cancers, which are distinct entities but managed identically

Pathogenesis and Genetics

Approximately 85-90% of cases are sporadic, while 10-15% are hereditary Germline BRCA1 mutations carry a 39-58% absolute risk, and BRCA2 mutations carry a 13-29% risk. Initial workup must include germline BRCA1/2 testing; if wild-type, somatic testing is recommended to guide PARP inhibitor use.

Screening and Prevention

There is no effective screening for the general population; CA-125 and transvaginal ultrasounds lack sensitivity and specificity. High-risk women (BRCA mutated) should consider risk-reducing salpingo-oophorectomy (RRSO) between ages 35-40. Oral contraceptives used for over five years can reduce risk by 50%.

Primary Treatment:

Early Stage (I-II): Surgery for staging followed by 3-6 cycles of adjuvant platinum-based chemotherapy for high-risk patients.
Advanced Stage (III-IV): Treatment involves optimal cytoreduction (residual tumor <1 cm) followed by six cycles of carboplatin/paclitaxel. Neoadjuvant chemotherapy (NACT) is preferred for those unlikely to achieve optimal debulking.

Maintenance and Recurrence:

  • Maintenance: PARP inhibitors—Olaparib, Niraparib, or Rucaparib—are standard following a response to platinum therapy. Olaparib + Bevacizumab is a Category 1 recommendation for HRD-positive advanced disease.
  • Recurrence: Defined as platinum-sensitive (>6 months since last treatment) or resistant (<6 months). For platinum-resistant cases, the antibody-drug conjugate (ADC) Mirvetuximab soravtansine-gynx is indicated for folate receptor alpha (FRα) positive tumors.

Cervical Cancer

Cervical cancer is almost exclusively caused by persistent infection with oncogenic Human Papillomavirus (HPV) strains 16 and 18.

Prevention and Screening:

The 9-valent HPV vaccine is approved for males and females aged 9-45. Screening for ages 30-65 involves cytology alone every 3 years or co-testing with HPV DNA every 5 years.

Primary Treatment:

Recurrent/Metastatic Disease:

  • Standard first-line is a platinum doublet plus bevacizumab.
  • For PD-L1 positive tumors (CPS ≥1), adding pembrolizumab to this regimen is a Category 1 preferred recommendation.
  • Second-line options include the ADC Tisotumab-vedotin-tfty, which requires strict ocular prophylaxis (steroid/lubricating drops and ice packs).

Endometrial Cancer

The primary etiology is excess estrogen exposure. Management has shifted toward molecular classification based on Cancer Genome Atlas (TCGA) subtypes.

Pathogenesis and Molecular Subtypes:

  • POLE mutations: Good prognosis.
  • MSI-H/dMMR: Intermediate prognosis; highly responsive to immunotherapy.
  • p53 mutant: Poor prognosis; requires aggressive multimodality care.
  • Lynch Syndrome: Universal testing for DNA mismatch repair (MMR) is mandatory; mutation carriers have a 40-60% lifetime risk.
    • Primary Treatment:
        ◦ Early Stage (I-II): Surgery (total hysterectomy/BSO) is primary; vaginal brachytherapy is used for those at risk of local recurrence.
        ◦ Advanced Stage (III-IV): Standard frontline therapy is carboplatin/paclitaxel. Recent Category 1 recommendations include adding pembrolizumab or dostarlimab to this doublet regardless of MMR status.
    • Recurrence: Endocrine therapy (Progestins, Tamoxifen) is used for low-grade, ER/PR-positive disease. For tumors that are not MSI-H/dMMR, Lenvatinib + Pembrolizumab is the preferred regimen for those who have progressed on prior systemic therapy.
    Supportive Care and Survivorship
    • Hypersensitivity (HSR): Platinum reactions typically occur after 6-8 exposures, while taxane reactions occur within minutes of the first or second dose. Severe HSR requires stopping the infusion and administering H1/H2 blockers and corticosteroids.
    • Alopecia: The Dignicap Cooling System is FDA-approved to reduce hair loss by cooling the scalp to constrict blood vessels during treatment.
    • Late Effects: Chronic issues include vaginal stenosis (managed with dilators and moisturizers), premature menopause (managed with hormone or non-hormonal therapy), and mood disorders.

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