What is the recommended management approach for uterine cancer?

Management of Uterine Cancer

Total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO) plus comprehensive surgical staging via minimally invasive approach is the cornerstone of treatment for apparent uterine-confined endometrial cancer. 1, 2, 3

Primary Surgical Management

Standard Surgical Approach

• TH/BSO with lymph node assessment is the primary treatment for apparent uterine-confined endometrial carcinoma unless fertility preservation is desired and criteria are met 1, 2
• Minimally invasive surgery (laparoscopic or robotic) is strongly preferred over laparotomy, providing equivalent oncologic outcomes with lower surgical site infection rates, reduced transfusion requirements, decreased venous thromboembolism, shorter hospital stays, and lower costs 1, 2, 3
• Robotic surgery offers particular advantage in obese patients with significantly lower major complication rates compared to laparotomy 3
• Endometrial carcinoma must be removed en bloc—intraperitoneal morcellation or tumor fragmentation should be avoided to prevent spreading cancerous tissue and compromising pathological assessment 1, 3

Comprehensive Surgical Staging Components

• Systematic exploration, inspection, and palpation of the entire abdomen including liver, diaphragm, omentum, and all peritoneal surfaces 1, 2, 3
• Peritoneal cytology should still be obtained despite no longer affecting FIGO staging, as positive cytology remains an adverse risk factor 1, 3
• Lymph node assessment is critical for prognostic information that directly impacts adjuvant treatment decisions 1, 2
  • Pelvic lymph nodes from external iliac, internal iliac, obturator, and common iliac regions should be evaluated 1
  • Para-aortic nodal evaluation from inframesenteric and infrarenal regions for high-risk tumors (deeply invasive lesions, high-grade histology, serous carcinoma, clear cell carcinoma, or carcinosarcoma) 1
  • Sentinel lymph node mapping may be considered as an alternative approach 1
  • Excision of any suspicious or enlarged lymph nodes in pelvic or aortic regions is essential 1
• Omentectomy should be performed for serous adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma histology 1, 2

Pathologic Assessment Requirements

The pathology report must include 1:

• Ratio of depth of myometrial/stromal invasion to myometrial thickness
• Cervical involvement including depth of stromal invasion
• Tumor size and location (fundus vs. lower uterine segment/cervix)
• Histologic subtype with grade
• Lymphovascular space invasion status
• Fallopian tube/ovarian involvement
• Peritoneal cytology results
• Nodal status when resected (level of involvement, size of metastasis)

Molecular Testing and Risk Stratification

Universal Testing Requirements

• Universal testing of all endometrial carcinomas for MMR gene deficiency should be performed on the final hysterectomy specimen 1, 2
• MLH1 loss should be further evaluated for promoter methylation to assess epigenetic processes 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, 2
• Comprehensive genomic profiling is encouraged when feasible 2, 3

Genetic Counseling Indications

• Patients <50 years of age should be screened for genetic mutations 1
• Those with strong family history of endometrial and/or colorectal cancer require genetic counseling even if dMMR-negative 1
• Patients with Lynch syndrome have up to 60% lifetime risk for endometrial cancer 1

Adjuvant Treatment by Stage and Risk

Stage IA Disease (Confined to Endometrium or <50% Myometrial Invasion)

• Grade 1-2: Observation alone is standard 2
• Grade 3: Consider vaginal brachytherapy or observation 2

Stage IB Disease (≥50% Myometrial Invasion)

• Grade 1-2 without adverse risk factors: Observation or vaginal brachytherapy 2
• Grade 1-2 with adverse risk factors: Consider vaginal brachytherapy and/or pelvic radiation therapy 2
• Grade 3: External pelvic radiotherapy with or without vaginal brachytherapy boost, or vaginal brachytherapy alone 3

Stage II Disease (Cervical Involvement)

• Stage IIA: Optional vaginal brachytherapy for all patients 2
• Stage IIB, grade 1-2: Consider pelvic RT and vaginal brachytherapy 2

Stage III-IV and Recurrent Disease

• Chemotherapy is the mainstay of treatment for advanced and recurrent disease 1, 2, 4
• For HER2-positive uterine serous carcinoma: Carboplatin/paclitaxel/trastuzumab is the preferred regimen (category 2A) with median PFS of 17.9 versus 9.3 months compared to control arms 2, 3
• For carcinosarcomas: Ifosfamide/paclitaxel (category 1) or carboplatin/paclitaxel 5, 4
• Adjuvant radiotherapy (external beam and/or vaginal brachytherapy) decreases local recurrences but has not shown overall survival benefit 4

Special Histologic Subtypes

Serous and Clear Cell Carcinoma

• Treat as high-grade epithelial tumors requiring aggressive multimodality therapy 2
• These should be managed similarly to advanced-stage disease even when apparently confined to the uterus 1

Carcinosarcomas (Malignant Mixed Müllerian Tumors)

• Now recognized as metaplastic carcinomas and should be treated as high-risk endometrial carcinomas rather than sarcomas 4
• More than 35% present with extrauterine disease at diagnosis 4
• Comprehensive surgical staging followed by systemic chemotherapy recommended for both early and advanced stage disease 4
• Carboplatin-paclitaxel is the most commonly used regimen in adjuvant and advanced settings 4

Uterine Sarcomas

• Total abdominal hysterectomy is the standard primary treatment for all localized uterine sarcomas 5
• Routine lymphadenectomy is not indicated as lymph node involvement is less than 5% 5
• For stage I high-grade sarcoma: Observation alone or consideration of adjuvant chemotherapy (category 2B) 5
• For stage II-III: Chemotherapy and/or tumor-directed radiation therapy with multimodality approach 5
• Hormone receptor testing should be performed as approximately 50% express estrogen/progesterone receptors 5

Fertility-Sparing Options

Strict Eligibility Criteria (All Must Be Met)

• Well-differentiated (grade 1) endometrioid adenocarcinoma on D&C confirmed by expert pathology review 1
• Disease limited to the endometrium on MRI (preferred) or transvaginal ultrasound (stage IA disease) 1
• Absence of suspicious or metastatic disease on imaging 1
• No contraindications to medical therapy or pregnancy 1

Management Approach

• Patients must be counseled that fertility-sparing option is NOT standard of care for endometrial carcinoma treatment 1
• Consultation with infertility specialist recommended prior to therapy 1
• Consider genetic counseling/testing if not already done 1
• Progestin-based therapy: Medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day) 3
• Endometrial sampling every 3-6 months with continued progestin therapy if not actively trying to conceive 1
• TH/BSO with staging required if endometrial cancer still present at 6 months or after childbearing is complete 1

Medically Inoperable Patients

• Tumor-directed radiation therapy is the primary option 1
• Consider hormone therapy in select patients with well-differentiated, hormone receptor-positive tumors 1

Surveillance After Treatment

Follow-Up Schedule

• Physical exam every 3-6 months for 2 years, then every 6 months or annually 1, 2
• Vaginal cytology every 6 months for 2 years, then annually 2
• Patient education regarding symptoms of recurrence, lifestyle modifications, obesity management, exercise, and nutrition counseling 1

Imaging and Laboratory

• CA-125 is optional for monitoring 1, 2
• Chest X-ray annually (category 2B) 2
• CT/MRI as clinically indicated based on symptoms or clinical findings 1, 2
• Imaging should not be performed routinely in asymptomatic patients 1

Critical Pitfalls to Avoid

• Never perform uterine morcellation without ruling out malignancy—this risks spreading cancerous tissue throughout the peritoneal cavity and compromises pathological assessment 3
• Do not rely on clinical staging alone—it underestimates disease extent in 15-20% of patients 1
• Preoperative radiotherapy is NOT recommended for stage I disease—it cannot be planned according to specific histoprognostic factors and constitutes overtreatment 3
• Do not skip lymph node assessment in surgical candidates—it provides critical prognostic information that directly impacts adjuvant treatment decisions 1
• Negative endometrial biopsy in symptomatic patients must be followed by fractional D&C under anesthesia—office biopsy has approximately 10% false-negative rate 1