Management of Uterine Cancer
Primary Surgical Management
Total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO) is the cornerstone of treatment for apparent uterine-confined endometrial cancer and should be performed via minimally invasive approach (laparoscopic or robotic) whenever feasible. 1, 2
Surgical Approach and Staging
Perform comprehensive surgical staging including systematic exploration, inspection, and palpation of the entire abdomen, peritoneal cytology (though no longer affects FIGO staging), and assessment of all peritoneal surfaces 1, 2
Lymph node assessment is critical for prognostic information that directly impacts adjuvant treatment decisions 1
- Pelvic lymph node dissection (external iliac, internal iliac, obturator, common iliac nodes) for staging purposes 1
- Para-aortic nodal evaluation (inframesenteric and infrarenal regions) for high-risk tumors: deeply invasive lesions, high-grade histology, serous carcinoma, clear cell carcinoma, or carcinosarcoma 1, 2
- Sentinel lymph node mapping may be considered as an alternative (category 2B) 1
Omentectomy should be performed for serous adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma histology 1, 2
Modified radical hysterectomy (Piver type II) is indicated for stage II cancers with macroscopic cervical lesions 2
Critical Surgical Principles
Endometrial carcinoma must be removed en bloc; avoid intraperitoneal morcellation or tumor fragmentation to optimize outcomes 1
Minimally invasive techniques are preferred due to lower surgical site infection rates, reduced transfusion requirements, decreased venous thromboembolism, shorter hospital stays, and lower costs without compromising oncologic outcomes 1
Adjuvant Treatment by Stage and Risk
Stage IA (Confined to Endometrium or <50% Myometrial Invasion)
- Grade 1-2: Observation alone is standard 2
- Grade 3: Consider vaginal brachytherapy or observation 1, 2
Stage IB (≥50% Myometrial Invasion)
- Grade 1-2 without adverse risk factors: Observation or vaginal brachytherapy 1, 2
- Grade 1-2 with adverse risk factors (LVSI, tumor size, location): Vaginal brachytherapy and/or pelvic radiation therapy 1, 2
- Grade 3: External pelvic radiotherapy with or without vaginal brachytherapy boost, or vaginal brachytherapy alone 1, 2
Stage II (Cervical Involvement)
- Stage IIA: Optional vaginal brachytherapy for all patients 1
- Stage IIB, Grade 1-2: Pelvic RT and vaginal brachytherapy 1
- Stage IIB, Grade 3: Pelvic RT and vaginal brachytherapy; chemotherapy may be added (category 2B) 1
Stage III (Extrauterine Disease)
For stage III disease, postoperative external radiotherapy with brachytherapy should be undertaken, with strong consideration for combined chemoradiation given improved recurrence-free and overall survival. 2
Stage IIIA (noninvasive, confined to fundus or positive cytology only): Observation; Grade 3 tumors can add vaginal brachytherapy or pelvic RT with/without chemotherapy 1
All other Stage IIIA tumors:
- Tumor-directed RT with or without chemotherapy, OR
- Chemotherapy with or without RT, OR
- Pelvic RT with or without vaginal brachytherapy 1
Stage IIIB and IIIC (completely resected): Chemotherapy and/or tumor-directed RT regardless of histologic grade 1
Stage IV (Distant Metastases)
Cytoreductive surgery with TH/BSO and maximal debulking of metastatic disease is the standard of care when performance status permits, as this offers the best chance for improved overall survival. 3
Stage IVA: Debulking surgery including TH/BSO, bowel resection if necessary, partial/total bladder resection with urinary diversion if required, and pelvic clearance as indicated 3
Stage IVB: Cytoreductive surgery with paramedial approach when feasible, with goal of maximal tumor debulking; include pelvic and para-aortic lymph node assessment and omentectomy 3
Post-surgical adjuvant options:
If surgery not feasible: Consider palliative radiotherapy for symptom control or TH/BSO by abdominal approach if preferable to radiotherapy alone 3
Special Histologic Subtypes
Serous Carcinoma and Clear Cell Carcinoma
- Treat as high-grade epithelial tumors requiring aggressive multimodality therapy 1, 4
- For HER2-positive uterine serous carcinoma: Carboplatin/paclitaxel/trastuzumab is the preferred regimen (category 2A) for stage III/IV disease or first-line recurrent disease 1
Carcinosarcoma (Malignant Mixed Müllerian Tumor)
- Now classified and treated as high-grade epithelial carcinomas, not sarcomas 1, 4
- Preferred chemotherapy: Ifosfamide/paclitaxel (category 1) or carboplatin/paclitaxel 1, 4
- Comprehensive surgical staging followed by systemic chemotherapy for both early and advanced stage disease 4
- Adjuvant radiotherapy decreases local recurrences but has not shown overall survival benefit 4
Uterine Sarcomas (Leiomyosarcoma, Endometrial Stromal Sarcoma, Undifferentiated Sarcoma)
Total abdominal hysterectomy is the standard primary treatment for all localized uterine sarcomas; routine lymphadenectomy is NOT indicated as lymph node involvement is less than 5%. 5
Stage I high-grade sarcoma: Observation alone or consider adjuvant chemotherapy (category 2B) 5
Stage II-III disease: Chemotherapy and/or tumor-directed radiation therapy; multimodality therapy typically recommended 5
Systemic therapy options:
Hormone receptor-positive tumors (approximately 50% of leiomyosarcomas express ER/PR): Consider hormonal therapy for recurrent disease with medroxyprogesterone acetate, megestrol acetate, aromatase inhibitors, or GnRH analogs 1, 5
Molecular Testing and Personalized Approaches
- Universal testing of endometrial carcinomas for MMR gene deficiency should be performed on the final hysterectomy specimen 1
- MLH1 loss should be further evaluated for promoter methylation 1
- Genetic counseling and testing recommended for all other MMR abnormalities 1
- Estrogen receptor testing should be performed in stage III, IV, and recurrent disease settings 1
- Comprehensive genomic profiling is encouraged when feasible 1
Surveillance After Treatment
- Physical exam every 3-6 months for 2 years, then every 6 months or annually 1
- Vaginal cytology every 6 months for 2 years, then annually 1
- Patient education regarding symptoms of recurrence 1
- CA-125 optional for monitoring 1
- Chest x-ray annually (category 2B) 1
- CT/MRI as clinically indicated 1
- High-grade sarcoma patients: Follow every 3-4 months in first 2-3 years, then twice yearly up to fifth year, then annually; regular chest imaging to detect pulmonary metastases 5
Common Pitfalls to Avoid
- Do not rely on preoperative imaging alone to distinguish between stage I and stage II disease, as no examination is sufficiently sensitive and specific 2
- Avoid inadequate surgical staging, which leads to suboptimal treatment decisions and decreased survival rates 3
- Do not overlook the importance of maximal cytoreduction in advanced disease, as incomplete debulking significantly worsens outcomes 3
- CA-125 has no diagnostic value for endometrial cancer but may predict extra-uterine extension at levels >35 U/ml 2
- Fertility-sparing options should only be considered in well-differentiated (grade 1) endometrioid adenocarcinoma limited to the endometrium in patients who wish to preserve fertility 2
- Ovarian preservation may be considered in young women (<50 years) with low-grade, early-stage endometrioid endometrial cancer without worsening overall survival 2