Adjuvant Radiation Therapy in Endometrial Cancer

Risk Stratification for Adjuvant Therapy

The National Comprehensive Cancer Network recommends adjuvant radiation therapy in endometrial cancer should be tailored based on disease stage, histologic grade, depth of myometrial invasion, and lymphovascular space invasion, with vaginal brachytherapy alone recommended for most patients with uterine-confined disease and combined modality treatment for advanced stages 1, 2
Patients with grade 1-2 endometrioid tumors with no invasion or <50% myometrial invasion and no other high-risk features can safely be observed after hysterectomy without adjuvant therapy, as no evidence supports routine use of adjuvant treatment for patients with disease confined to the uterus 2, 3
For patients with intermediate-risk disease, adjuvant vaginal brachytherapy is recommended, as the PORTEC-2 trial demonstrated that vaginal brachytherapy alone provides equivalent vaginal and pelvic control rates compared to external beam radiation therapy with less toxicity 2, 3, 4

For stage III-IV disease, systemic therapy forms the mainstay of treatment, often combined with external beam radiation therapy and/or vaginal brachytherapy, as combined modality adjuvant therapy provides better therapeutic benefit compared to single-modality therapy for stage III disease 1, 5
The PORTEC-3 trial showed improved 5-year overall survival with chemoradiotherapy versus radiotherapy alone for high-risk endometrial cancer, with patients with serous cancers and stage III disease benefiting most from the addition of systemic therapy to radiation 1

External beam radiation therapy significantly reduces locoregional recurrence but has not consistently shown overall survival benefit in early-stage disease, according to the Annals of Oncology 2, 3
Vaginal brachytherapy provides excellent vaginal control with minimal toxicity, and can be used alone for intermediate and high-intermediate risk disease, as recommended by the National Comprehensive Cancer Network 1, 2, 3

Whole abdominal radiation therapy is considered inferior to chemotherapy and too toxic, and is no longer recommended, as stated by the National Comprehensive Cancer Network 1, 5
Overtreatment of low-risk patients with unnecessary radiation should be avoided, and undertreatment of high-risk patients with vaginal brachytherapy alone when external beam radiation therapy is indicated may lead to increased pelvic recurrence, according to the National Comprehensive Cancer Network and the Journal of the National Comprehensive Cancer Network 3, 6, 5

The National Comprehensive Cancer Network recommends obtaining radiologic imaging to assess for nodal involvement and determine if surgical restaging is needed for patients with unknown lymph node status 7
Tumor grade is a critical factor in risk stratification, with Grade 1, 2, or 3 classifications 8
Histologic subtype, including endometrioid vs non-endometrioid, is also an important consideration in risk stratification 8, 9, 10

The National Comprehensive Cancer Network recommends no adjuvant therapy for patients with low-risk disease, including those with negative imaging 9, 8, 10
For patients with high-intermediate risk disease, pelvic external beam radiation therapy with or without vaginal brachytherapy should be considered, particularly for those with deep myometrial invasion or Grade 3 histology 9, 8, 10
The National Comprehensive Cancer Network recommends combined external beam radiation and systemic chemotherapy for patients with high-risk disease, including those with Stage IB Grade 3 with adverse risk factors or non-endometrioid histology 10, 11

The National Comprehensive Cancer Network recommends carboplatin/paclitaxel as a preferred systemic chemotherapy option for Stage I disease with high-risk features due to lower toxicity 9, 8
Cisplatin/doxorubicin combinations are also an option, but have higher toxicity 9, 8
The GOG 249 trial showed that adequate cycles of chemotherapy are essential when used in combination with vaginal brachytherapy or pelvic EBRT 10

The National Comprehensive Cancer Network recommends annual visits after 5 years, with more frequent evaluations in the first 3 years 9, 8