Gynecology Topic 48. Principles of cancer therapy

I. General Principles

Decision Factors and Goals

• Cancer therapy is individualized by tumor type, stage, grade, histology, molecular markers, patient fitness and fertility wishes.
• Histologic confirmation and staging are required before definitive treatment whenever possible.
• Multidisciplinary planning: Gynecologic oncology, medical oncology, radiation oncology, radiology, pathology and fertility/palliative teams when needed.
• Treatment goals:

• Curative: Eradicate disease.
• Adjuvant: Treat microscopic residual disease after surgery.
• Neoadjuvant: Shrink tumor before definitive surgery/radiation.
• Palliative: Symptom control, prolong survival and preserve quality of life.

II. Surgery

Types and Principles

• Types: Curative, palliative, conservative/fertility-sparing, radical, cytoreductive/debulking.
• Main surgical principle: Remove tumor with adequate margins and stage lymph nodes/peritoneum when indicated.
• Simple excision: Small localized vulvar/vaginal/cervical lesions.
• Total abdominal hysterectomy (TAH): Removal of uterus and cervix; adnexal removal depends on cancer type, age and indication.
• Radical hysterectomy / Wertheim procedure: Uterus + cervix + parametria + upper vagina + pelvic lymph node assessment; used for selected cervical cancer.
• Radical vulvectomy: Vulvar tumor surgery + inguinal lymph node assessment; modern surgery often uses individualized radical local excision when safe.
• Palliative surgery: Control bleeding, obstruction, fistula, pain or infection.
• Complications: Bleeding, infection, bladder/ureter/bowel injury, thromboembolism, lymphoedema, infertility and sexual dysfunction.

III. Radiotherapy

Types and Uses

• Radiotherapy: Ionizing radiation causes DNA damage and tumor cell death.
• Types by intent: Curative, adjuvant or palliative.
• External beam radiotherapy (EBRT): Treats pelvis/groin/para-aortic fields depending on tumor.
• Brachytherapy: Internal radiation close to tumor; important in cervical, endometrial and vaginal cancers.
• Combined therapy: EBRT + brachytherapy; cervical cancer often uses concurrent cisplatin chemoradiation.
• Palliative radiotherapy: Bleeding, pain, bone/brain metastasis or obstruction symptoms.

Side Effects

• Acute: Fatigue, skin reaction, diarrhea, cystitis, vaginal irritation, marrow suppression with large pelvic fields.
• Late: Vaginal stenosis/dryness, ovarian failure, bowel obstruction/fistula, radiation cystitis/proctitis, pelvic fracture, lymphoedema.

IV. Chemotherapy

Timing and Examples

• Chemotherapy: Systemic cytotoxic treatment for proliferating cells.
• Types by timing/intent: Neoadjuvant, adjuvant, concurrent chemoradiation or palliative.
• Platinum-based therapy: Common in cervical, ovarian and endometrial cancers.
• Ovarian epithelial cancer: Carboplatin + paclitaxel ± bevacizumab; PARP inhibitor maintenance in selected BRCA/HRD or platinum-responsive disease.
• Cervical cancer: Cisplatin-based chemoradiation; recurrent/metastatic disease may use platinum/taxane ± bevacizumab ± pembrolizumab depending on markers.
• Endometrial cancer: Carboplatin + paclitaxel; immunotherapy may be added/used in advanced or recurrent disease depending on MMR/MSI status and protocol.
• Gestational trophoblastic neoplasia: Methotrexate or actinomycin D for low-risk disease; EMA-CO for high-risk disease.
• EMA-CO: Etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine (Oncovin).

Toxicity

• General: Myelosuppression, nausea/vomiting, mucositis, alopecia, fatigue, infertility/ovarian failure.
• Cisplatin: Nephrotoxicity, ototoxicity, neuropathy.
• Paclitaxel: Neuropathy, hypersensitivity, myelosuppression.
• Anthracyclines: Cardiotoxicity; bleomycin: pulmonary toxicity.

V. Hormonal, Targeted and Immune Therapy

Hormonal Therapy

• Tamoxifen: Selective estrogen receptor modulator (SERM).
• Aromatase inhibitors: Letrozole/anastrozole/exemestane → Inhibit estrogen synthesis.
• GnRH agonists: Leuprolide/goserelin → Ovarian suppression.
• Progestins: Selected low-grade hormone receptor-positive endometrial cancer or atypical hyperplasia.
• Uses: Breast cancer, selected endometrial cancers, selected recurrent ovarian sex cord-stromal or low-grade serous tumors.

Targeted and Immune Therapy

• Ovarian cancer: Bevacizumab (anti-VEGF monoclonal antibody), olaparib/niraparib/rucaparib (PARP inhibitors, especially BRCA/HRD or platinum-responsive disease), pembrolizumab only in selected biomarker-defined settings.
• Endometrial cancer: Pembrolizumab/dostarlimab especially in dMMR/MSI-H disease; pembrolizumab + lenvatinib in selected recurrent advanced disease; everolimus (mTOR inhibitor) in selected contexts.
• Cervical cancer: Bevacizumab in selected recurrent/metastatic regimens; pembrolizumab in selected PD-L1-positive recurrent/metastatic or high-risk locally advanced settings.
• Common targeted/immunotherapy toxicities: Hypertension/proteinuria/bleeding with bevacizumab; cytopenias with PARP inhibitors; immune-related colitis, hepatitis, pneumonitis and endocrinopathies with checkpoint inhibitors.

VI. Response, Follow-Up and Palliation

Response and Follow-Up

• Assess response by symptoms, examination, imaging and tumor markers when useful.
• Response categories: Complete response, partial response, stable disease, progressive disease.
• Useful tumor markers: CA-125 in selected ovarian cancer follow-up; β-hCG in gestational trophoblastic neoplasia; SCC antigen in selected squamous cancers.
• Follow-up detects recurrence and manages late toxicity: Lymphoedema, neuropathy, bladder/bowel dysfunction, vaginal stenosis, premature menopause and psychosocial problems.

Palliative Care

• Integrate early in advanced/recurrent disease.
• Targets: Pain, bleeding, discharge, obstruction, ascites, nausea, dyspnea, anxiety/depression.
• Options: Palliative radiotherapy, chemotherapy/systemic therapy, transfusion, paracentesis, stents/nephrostomy and selected surgery.