Management of Adenosquamous Carcinoma of the Uterus
Treat uterine adenosquamous carcinoma as a high-risk endometrial cancer using the same aggressive multimodality approach recommended for serous and clear cell carcinomas: primary surgical staging with total hysterectomy/bilateral salpingo-oophorectomy followed by platinum-taxane chemotherapy with or without tumor-directed radiation therapy. 1
Classification and Risk Stratification
Adenosquamous carcinoma of the endometrium should be managed identically to pure adenocarcinoma of the same grade and stage, as historical data demonstrate no significant differences in incidence, clinical behavior, radiation response, or prognosis between these entities 2.
However, when adenosquamous carcinoma exhibits high-grade features or aggressive histology, classify it alongside serous adenocarcinomas, clear cell adenocarcinomas, and carcinosarcomas as a high-risk malignant epithelial tumor (grade 3 equivalent). 1
These aggressive histologic variants demonstrate higher incidence of extrauterine disease at presentation and patterns of failure that mimic ovarian cancer 1.
Preoperative Evaluation
Obtain CA-125 levels before surgery, as recommended by both NCCN and SGO for high-risk endometrial tumors 1.
Perform MRI or CT imaging to assess for extrauterine disease; PET imaging may also be useful in detecting occult metastases 1.
Evaluate for pelvic masses, abnormal cervical cytology, or ascites in addition to the typical presentation of postmenopausal bleeding 1.
Primary Surgical Management
Perform comprehensive surgical staging that mirrors the approach for ovarian cancer rather than standard endometrial cancer staging: 1
Total hysterectomy with bilateral salpingo-oophorectomy 1, 3
Peritoneal lavage for cytology 1
Omental biopsy or omentectomy 1
Peritoneal biopsies from multiple sites 1
Maximal tumor debulking if gross disease is present 1
Fertility-sparing therapy is absolutely contraindicated due to the aggressive nature and high risk of distant metastases even in apparent early-stage disease 1.
Adjuvant Therapy by Stage
Stage IA Without Myometrial Invasion
Choose one of three options based on individual risk factors: 1
- Observation alone
- Chemotherapy
- Tumor-directed radiation therapy
Stage IB or Higher (All Other Stages)
Administer platinum-taxane chemotherapy (carboplatin plus paclitaxel) with or without tumor-directed radiation therapy as the preferred approach. 1, 3
Platinum-taxane regimens improve survival in uterine serous and clear cell adenocarcinoma, and this benefit extends to other high-risk histologies 1.
Chemotherapy with or without radiation therapy is more effective than radiation therapy alone 1.
Whole abdominopelvic radiation therapy is no longer recommended as primary treatment because routine use is not appropriate and chemotherapy-based regimens demonstrate superior efficacy 1.
Tumor-Directed Radiation Therapy Definition
Tumor-directed radiation refers to external-beam radiation therapy and/or brachytherapy directed at sites of known or suspected tumor involvement 1.
This typically includes the pelvis with or without the para-aortic region 1.
Whole abdominal radiation therapy does not qualify as tumor-directed radiation therapy 1.
Advanced or Metastatic Disease
Adequately Debulked Stage III-IV
- Chemotherapy with or without tumor-directed radiation therapy 1
- Whole abdominopelvic radiation with or without vaginal brachytherapy (category 3, less preferred) 1
Inadequately Debulked Stage III-IV
- Systemic chemotherapy is mandatory 1
Specific Chemotherapy Regimens
First-line platinum-taxane options: 1
- Carboplatin plus paclitaxel (most commonly used, response rate approximately 40-54%) 1
- Cisplatin plus doxorubicin plus paclitaxel (slightly improved survival of 15 vs 12 months but significantly increased toxicity) 1
Critical Pitfalls to Avoid
Do not treat adenosquamous carcinoma with observation alone unless it is truly stage IA without myometrial invasion 1.
Do not rely on sentinel lymph node mapping alone—if performed, proceed with particular caution given the high risk of occult metastases 1.
Do not use whole abdominal radiation as primary adjuvant therapy instead of chemotherapy, as this approach is outdated and inferior 1.
Do not confuse adenosquamous carcinoma with adenoacanthoma (benign squamous elements), which has a more favorable prognosis 2.