What is the management of endometrial adenocarcinoma?

Management of Endometrial Adenocarcinoma

Total hysterectomy with bilateral salpingo-oophorectomy is the cornerstone of treatment for endometrial adenocarcinoma, with adjuvant therapy decisions based on surgical-pathologic risk stratification. 1, 2

Initial Diagnostic Workup

• Obtain tissue diagnosis through endometrial biopsy or dilation and curettage to confirm adenocarcinoma histology 2
• Perform pelvic MRI with dynamic contrast enhancement to assess myometrial invasion depth and cervical stromal involvement—this is the most accurate imaging modality 2
• Order complete blood count, liver function tests, and renal function profiles as part of preoperative evaluation 1, 2
• Consider CA125 measurement as levels >35 U/ml may predict extra-uterine disease extension 2
• Obtain transvaginal ultrasound to evaluate endometrial thickness, myometrial invasion, and rule out ovarian involvement 2
• Request CT chest/abdomen/pelvis or PET-CT for clinically advanced disease to assess for distant metastases 1
• Pursue molecular characterization and comprehensive genomic profiling when feasible, as this increasingly guides treatment decisions 2

Primary Surgical Management

Standard surgery consists of total hysterectomy with bilateral salpingo-oophorectomy without vaginal cuff excision 1, 2

Surgical Approach

• Perform minimally invasive surgery (laparoscopic or robotic) rather than laparotomy whenever possible—this provides equivalent oncologic outcomes with superior perioperative benefits 1, 2
• Use robotic surgery particularly in obese patients as it significantly reduces major complication rates compared to laparotomy 2
• Conduct systematic exploration, inspection, and palpation of the entire abdomen including liver, diaphragm, omentum, and peritoneal surfaces 1, 2
• Obtain peritoneal cytology at the start of surgery, though it no longer affects FIGO staging 1, 2
• Perform omentectomy for serous, clear cell, and carcinosarcoma histologies given increased risk of advanced-stage disease 1

Lymphadenectomy Considerations

• Do NOT perform routine systematic pelvic lymphadenectomy in low-risk disease (Grade 1-2, <50% myometrial invasion) as it provides no survival benefit 1, 3, 4
• Consider lymphadenectomy for intermediate-to-high-risk disease including Grade 3 tumors, deep myometrial invasion, or non-endometrioid histology 1, 4
• When lymphadenectomy is indicated, remove >10 nodes as this threshold correlates with improved survival 1
• Perform para-aortic lymphadenectomy up to the renal vessels when indicated, as 16% of node-positive patients have isolated para-aortic involvement and 77% of para-aortic metastases occur above the inferior mesenteric artery 1
• Consider sentinel lymph node dissection as a compromise between no dissection and full dissection in select cases 1

Special Surgical Considerations

• Preserve ovaries only in patients <45 years old with Grade 1 endometrioid cancer, <50% myometrial invasion, and no extra-uterine disease 1
• Perform salpingectomy if ovaries are preserved 1
• Do NOT preserve ovaries in patients with family history of ovarian cancer (BRCA mutation, Lynch syndrome)—offer genetic counseling instead 1
• Never perform uterine morcellation without ruling out malignancy as this risks spreading cancerous tissue and compromises pathological assessment 2

Risk Stratification and Adjuvant Therapy

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

• Observation alone without adjuvant therapy is standard, with 5-year disease-free survival approximately 93% 2, 3
• No radiation therapy is indicated for this group 3

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

• Choose between vaginal brachytherapy or observation alone 2
• Vaginal brachytherapy reduces pelvic/vaginal relapses but does NOT improve overall survival 3
• Reserve pelvic external beam radiation for patients with two of three major risk factors (age ≥60 years, Grade 2-3, lymphovascular space invasion) 1, 3

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

• Administer external pelvic radiotherapy with or without vaginal brachytherapy boost, OR vaginal brachytherapy alone 2
• Consider platinum-based chemotherapy for Stage II-III disease 4

Advanced/Metastatic Disease (Stage III-IV)

• Perform maximal surgical cytoreduction in patients with good performance status 1
• For HER2-positive uterine serous carcinoma or carcinosarcoma, use carboplatin/paclitaxel/trastuzumab triplet therapy as the preferred regimen 2
• This triplet therapy achieves median PFS of 17.9 months versus 9.3 months for non-trastuzumab regimens (P=0.013) 2
• Administer pelvic radiotherapy to increase pelvic control in Stage III disease 1
• Use cisplatin, carboplatin, anthracyclines, and paclitaxel as active single agents showing significant objective response rates 1

Medically Inoperable Patients

• Treat with external beam radiotherapy combined with brachytherapy for patients unfit for surgery 1, 4
• Consider vaginal hysterectomy with bilateral salpingo-oophorectomy in select low-risk patients who cannot undergo standard surgery 1
• Use hormonal treatment as an alternative in some medically inoperable cases 1

Fertility-Sparing Management

Refer young patients with Grade 1 endometrioid adenocarcinoma limited to the endometrium who desire fertility preservation to specialized centers 2

• Confirm diagnosis through dilation and curettage by a specialist gynaecopathologist—this is superior to pipelle biopsy 2
• Perform pelvic MRI to exclude myometrial invasion and adnexal involvement 2
• Treat with medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day) 2
• Maintain close follow-up as recurrent disease may require definitive surgical management 3

Critical Pitfalls to Avoid

• Do NOT administer adjuvant progestational agents in low-stage disease as they do not increase survival 1, 3
• Do NOT use preoperative radiotherapy for Stage I disease as it constitutes overtreatment and cannot be tailored to histoprognostic factors 2
• Do NOT rely on clinical staging alone as it underestimates disease extent in some cases 2
• Do NOT perform routine CA125 testing as there is no evidence for clinical usefulness despite correlation with adverse features 1

Follow-Up Protocol

• Conduct history, physical, and gynecological examination every 3-4 months for the first 3 years 1, 3
• Extend follow-up intervals to 6 months during years 4-5 1, 3
• Perform annual examinations thereafter 1, 3
• Focus on early detection of vaginal or pelvic relapses as these may be amenable to curative treatment 1
• Do NOT perform routine PAP smears or systematic radiography as these are of unproven benefit 1