What is the management of endometrial carcinoma?

Management of Endometrial Carcinoma

The management of endometrial carcinoma is a multimodality approach centered on total hysterectomy with bilateral salpingo-oophorectomy as the primary treatment, with adjuvant therapy decisions guided by surgical staging, histopathologic characteristics (grade, type, lymphovascular space invasion, myometrial invasion), and increasingly by molecular classification. 1

Initial Diagnostic Workup

Before any surgical intervention, obtain comprehensive preoperative evaluation:

• Tissue diagnosis through endometrial biopsy or dilation and curettage 2
• Pelvic MRI with dynamic contrast enhancement - this is the most accurate imaging modality for assessing myometrial invasion and cervical stromal involvement 2
• Transvaginal ultrasound to assess endometrial thickness, myometrial invasion, and rule out ovarian involvement 2
• Laboratory workup: complete blood count, liver function tests, renal function profiles 2
• CA125 measurement - while not diagnostic, levels >35 U/ml may predict extra-uterine extension 3
• Molecular characterization and comprehensive genomic profiling when feasible 1

Critical caveat: Preoperative imaging cannot reliably distinguish between stage I and stage II disease with sufficient sensitivity and specificity 3

Primary Surgical Management

Standard Surgical Approach

Total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO) is the cornerstone of treatment for apparent uterine-confined endometrial cancer 3, 2

The surgical procedure must include:

• Systematic exploration, inspection, and palpation of the entire abdomen including liver, diaphragm, omentum, and peritoneal surfaces 3, 2
• Peritoneal cytology (although it no longer affects FIGO staging) 3, 2
• Minimally invasive approach is strongly preferred over laparotomy, providing equivalent oncologic outcomes with superior perioperative benefits 2
• Robotic surgery offers particular benefit in obese patients, with significantly lower major complication rates compared to laparotomy 2

Lymph Node Assessment Strategy

The approach to lymphadenectomy depends on risk stratification:

• Routine systematic pelvic lymphadenectomy does NOT improve overall survival or disease-free survival in stage I endometrial cancer 2
• However, lymphadenectomy provides critical prognostic information that guides adjuvant therapy decisions 3, 2
• Pelvic nodal dissection should be performed for intermediate-to-high-risk disease 3, 2
• Para-aortic nodal evaluation is indicated for high-risk tumors: deeply invasive lesions, high-grade histology, serous adenocarcinoma, clear cell carcinoma, or carcinosarcoma 3
• Sentinel lymph node mapping may be considered in selected patients (category 2B recommendation) 3

Additional Surgical Considerations

• Omentectomy is commonly performed for serous adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma histology 3
• Modified radical hysterectomy (Piver type II) is recommended for stage II cancers with macroscopic cervical lesions 3

Risk Stratification for Adjuvant Therapy

Stratify patients based on: FIGO stage, histological type and grade, depth of myometrial invasion, lymphovascular space invasion, lymph node status, and molecular classification 2

Low-Risk Disease (Grade 1-2, Stage IA)

• Surgery alone is adequate; follow-up without adjuvant therapy is standard 3, 2

Intermediate-Risk Disease (Grade 1-2, Stage IB)

• Options include vaginal brachytherapy or follow-up alone 3
• Vaginal brachytherapy is recommended to maximize local control with minimal side effects and no impact on quality of life 2

High-Risk Early Disease (Grade 3, Stage IB or Stage IC)

Two treatment options exist:

• External pelvic radiotherapy with or without vaginal brachytherapy boost (level of evidence B) 3
• Vaginal brachytherapy alone (level of evidence C) 3

Stage II Disease

When stage II disease is confirmed by positive endocervix or cervix biopsy:

• External radiotherapy with brachytherapy OR
• Brachytherapy followed by surgery OR
• Surgery as primary treatment followed by adjuvant radiotherapy according to prognostic factors 1

Stage III Disease

• Postoperative external pelvic radiotherapy with brachytherapy boost is standard 1, 3
• For stage IIIC with pelvic nodes involved: postoperative pelvic radiotherapy ± brachytherapy boost 1
• For stage IIIC with para-aortic nodes involved: extended postoperative radiotherapy (pelvic and para-aortic) ± brachytherapy 1
• Combined chemoradiation has shown improved recurrence-free and overall survival for high-risk endometrial cancer, particularly stage III disease 3

Advanced Disease (Stage III-IV)

For stage III disease when radical surgery is possible:

• Cytoreductive surgery remains the best way to improve overall survival 1
• Debulking surgery includes: total hysterectomy with BSO, bowel resection if possible, and partial/total bladder resection if possible 1, 3
• Resection should be as extensive as possible, followed by radiotherapy 1

For stage IVB disease:

• Optimal cytoreduction remains crucial 4
• Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery should be considered for cases deemed unresectable 4
• Multimodality adjuvant therapy combining radiotherapy and chemotherapy may benefit patients, even with disease spread beyond the pelvis 4

Systemic Therapy for Advanced/Recurrent Disease

HER2-Positive Disease

For HER2-positive uterine serous carcinoma or carcinosarcoma:

• Carboplatin/paclitaxel/trastuzumab triplet therapy is the preferred option (category 1 for serous carcinoma, category 2B for carcinosarcoma) 1
• This regimen is recommended for: (1) primary therapy for stage III/IV disease, or (2) first-line option for recurrent disease 1
• Median PFS was 17.9 versus 9.3 months for trastuzumab-containing versus control arms in stage III/IV disease (P=0.013) 1

Carcinosarcoma

• Carboplatin/paclitaxel is a preferred, category 1 option for carcinosarcoma histology 1
• For second-line/subsequent therapy: ifosfamide, ifosfamide/paclitaxel, and ifosfamide/cisplatin are options for carcinosarcoma only 1
• Ifosfamide/paclitaxel combination increased survival with OS of 13.5 months versus 8.4 months with ifosfamide alone 1

Special Populations

Fertility-Sparing Management

For patients with grade 1 endometrioid adenocarcinoma limited to the endometrium who wish to preserve fertility:

• Patients must be referred to specialized centers 1
• Diagnosis must be confirmed by specialist gynaecopathologist through dilatation and curettage (D&C), which is superior to pipelle biopsy 1
• Pelvic MRI should be performed to exclude overt myometrial invasion and adnexal involvement (expert ultrasound can be considered as alternative) 1
• Conservative medical treatment is based on progestins: medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day) 1
• Patients must be informed this is non-standard treatment and accept close follow-up with need for future hysterectomy 1

Lynch Syndrome Patients

• Surveillance of the endometrium by gynecological examination, transvaginal ultrasound, and aspiration biopsy starting from age 35 years (annually until hysterectomy) should be offered to all Lynch syndrome mutation carriers 1
• Prophylactic surgery (hysterectomy and bilateral salpingo-oophorectomy) using minimally invasive approach should be discussed at age 40 1

Medically Inoperable Patients

• External beam radiotherapy and/or brachytherapy are acceptable alternatives for patients with significant comorbidities precluding surgery 2
• If performance status is poor, total hysterectomy plus BSO by abdominal approach is preferable to treatment with radiotherapy alone 1

Critical Pitfalls to Avoid

• Never perform uterine morcellation without ruling out malignancy - this risks spreading cancerous tissue and compromises pathological assessment 2
• Do not rely on clinical staging alone - it underestimates disease extent in some cases 2
• Preoperative radiotherapy is NOT recommended for stage I disease - it cannot be planned according to specific histoprognostic factors and would constitute overtreatment 1
• Recognize that discrepancies between preoperative and final pathology occur frequently - be prepared to adjust treatment plans 2
• The impact of residual tumor after primary surgery is a critical factor affecting survival in advanced disease 4