What is the best adjuvant treatment for a patient with FIGO (International Federation of Gynecology and Obstetrics) stage 3C endometrial cancer (Ca endometrium) after staging laparotomy?

Best Adjuvant Treatment for FIGO Stage 3C Endometrial Cancer

For patients with FIGO stage 3C endometrial cancer after staging laparotomy, the optimal adjuvant treatment is combined chemoradiotherapy consisting of chemotherapy with carboplatin/paclitaxel plus external beam radiation therapy (EBRT).

Treatment Algorithm

First-line Adjuvant Treatment:

• Combined modality therapy with chemotherapy plus radiation therapy is recommended as the standard treatment for stage IIIC endometrial cancer 1
• The recommended chemotherapy regimen is carboplatin and paclitaxel 1, 2
• External beam radiation therapy (EBRT) should be included, with fields covering the pelvis 1
• Consider extended-field radiation to para-aortic nodes, especially for patients with positive para-aortic lymph nodes 1, 3
• Vaginal brachytherapy boost should be added to improve local control 3, 4

Sequencing Options:

• "Sandwich" approach: Initial chemotherapy, followed by radiation therapy, followed by remaining chemotherapy cycles 5
• Sequential approach: Complete chemotherapy followed by radiation therapy 5
• Concurrent approach: Cisplatin with radiation therapy, followed by carboplatin/paclitaxel 4

Evidence Supporting Combined Modality Treatment

Chemotherapy Evidence:

• GOG 122 established the role of adjuvant multiagent systemic chemotherapy for curative intent in patients with extrauterine disease 1
• Carboplatin plus paclitaxel is the current standard regimen based on efficacy and tolerability 1, 2
• Patients who received adjuvant chemotherapy alone (without radiation) had a 2.2-fold increased risk of recurrence and a 4.0-fold increased risk of death compared to those receiving combined therapy 1

Radiation Therapy Evidence:

• In a retrospective review of stage IIIC endometrial cancer, adjuvant radiation therapy significantly improved overall survival in patients with endometrioid histology, high-grade tumors, and positive para-aortic lymph nodes 1
• Extended-field radiation therapy (including para-aortic nodes) should be considered for patients with positive para-aortic nodes 1, 3
• No patient treated with extended-field radiation therapy developed para-aortic nodal recurrence in one study, compared to 4 recurrences in patients treated with pelvic radiation only 3

Combined Modality Evidence:

• The PORTEC-3 trial demonstrated improved 5-year overall survival with chemoradiotherapy versus radiotherapy alone (81.4% vs 76.1%) for high-risk endometrial cancer, with stage III patients benefiting most 1
• A multicenter retrospective review of stage IIIA endometrial carcinoma showed that surgery followed by both chemotherapy and radiation therapy provided the highest 5-year overall survival 1
• The RTOG 9708 phase 2 trial showed favorable overall survival and disease-free survival with combined modality treatment 1

Special Considerations

Molecular Profiling:

• Molecular analysis from the PORTEC-3 trial showed that tumors with p53 abnormalities benefited most from combined chemoradiotherapy (5-year RFS 59% vs 36%) 1
• Consider molecular profiling to guide treatment decisions, as ongoing trials are investigating molecular profile-based directed adjuvant treatment 1

Treatment Toxicity:

• Combined modality treatment may be associated with increased acute toxicity compared to single-modality treatment 1, 4
• Most common grade 3 toxicities include neutropenia, anemia, fatigue, and diarrhea 4
• Despite increased acute toxicity, most patients (78%) are able to complete the planned combined therapy 4

Common Pitfalls and Caveats

• Whole abdominal radiation therapy as a single modality is considered inferior to chemotherapy and too toxic; therefore, it is no longer recommended 1
• Undertreatment with radiation therapy alone or chemotherapy alone may lead to increased risk of recurrence compared to combined modality therapy 1
• Failure to extend radiation fields to cover para-aortic nodes in patients with positive para-aortic nodes may result in increased risk of para-aortic recurrence 1, 3
• Omitting vaginal brachytherapy may increase the risk of vaginal recurrence (4/20 without brachytherapy vs 0/10 with brachytherapy in one study) 3
• Emerging evidence suggests immunotherapy may play a role in treatment, particularly for tumors with specific molecular features, but this approach is still investigational 6