The American Society for Radiation Oncology (ASTRO) released a newly updated clinical guideline designed to provide recommendations on the use of radiation therapy and systemic therapy after surgery to treat patients with endometrial cancer. Published in Practical Radiation Oncology, the guideline updates 2014 recommendations and also considers the role of surgical staging and molecular profiling techniques in determining whether a patient should receive postoperative therapy (2022; https://doi.org/10.1016/j.prro.2022.09.002).
In the 8 years since the 2014 updates were issued, several important trials across risk groups and stages of endometrial cancer have reported on the role of adjuvant radiation therapy and systemic therapy, noted Beth A. Erickson, MD, FASTRO, Chair of the ASTRO Guidelines Task Force and Professor of Radiation Oncology at the Medical College of Wisconsin.
“Additionally, advances in surgical staging techniques, including sentinel lymph node mapping and pathologic ultrastaging, have changed the landscape of surgical management and influence the need for adjuvant therapy,” Erickson told Oncology Times. “The prognostic and predictive use of molecular profiling of endometrial cancer is now recognized and its impact on adjuvant therapy selection is increasing, with ongoing trials aiming to confirm this influence on endometrial cancer management. As a result, a revised ASTRO guideline acknowledging these important updates and the possible impact these advancements may have in the adjuvant treatment of endometrial cancer is warranted.”
Erickson and her colleagues on the task force considered new trials on the accuracy of surgical staging techniques and the increasing role of molecular profiling for endometrial tumors in guiding adjuvant therapy decisions. They noted that researchers have identified several potential biomarkers for endometrial cancer and are currently exploring whether these molecular markers can help determine which patients will benefit from adjuvant therapy.
The new guideline includes treatment algorithms for Stage I-II endometrial cancers, Stage I-II cancers with high-risk histologies, and Stage III-IVA cancers. It details the recommended use of external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), and chemotherapy for patients with different risk profiles, as well as which patients should not receive adjuvant therapy. Key recommendations include the following:
- Based on a patient's clinical-pathologic risk factors, radiation therapy is recommended to reduce the risk of locoregional recurrence. The choice of EBRT versus VBT in FIGO Stage I endometrial cancer should depend on lymph node assessment and uterine risk factors. EBRT is recommended for patients with Stage I disease with high-risk features, Stage II disease, or Stage III-IVA disease.
- Systemic chemotherapy should be effectively sequenced with radiation therapy for patients with high-risk histologies and/or Stage III-IVA disease to decrease the risk of distant and locoregional recurrence, respectively.
- When EBRT is indicated, the use of intensity-modulated radiation therapy (IMRT) with daily image guidance is associated with improved patient-reported outcomes and reduced side effects. Recommendations in the guideline also outline optimal radiation dosing, treatment planning, and delivery techniques based on the patient's cancer stage and histology.
- For surgical nodal staging, sentinel lymph node mapping is recommended over pelvic lymphadenectomy, and the use of adjuvant therapy should be based on a patient's pathologic ultrastaging status.
- Molecular tumor profiling is recommended and may be used to guide recommendations for adjuvant therapy.
Based on a systematic literature review of articles published through August 2021, a multidisciplinary taskforce including radiation oncologists, medical oncologists, and gynecological oncologists developed the guideline, which “also acknowledges the negative impact of systemic racial disparities on endometrial cancer outcomes,” according to ASTRO. “While the guideline is focused on the medical considerations for treatment, the taskforce also wanted to recognize the complex nature of access to care for underserved patient populations.”
Erickson pointed to a number of key takeaways for radiation oncologists to emerge from the new guideline.
“The choice of external beam radiation (EBRT) versus vaginal brachytherapy in FIGO Stage I endometrial cancer should depend on the performance and method of lymph node assessment and the uterine risk factors, including the degree of LVSI and histology, and patient age,” she stated. “EBRT decreases the risk of locoregional recurrence, especially in patients with FIGO Stage I disease with high-risk features or high-risk histologies, FIGO Stage II disease, and FIGO Stage III-IVA disease.”
When EBRT is indicated, the use of IMRT is associated with improved patient-reported outcomes and acute and late toxicity. Creation of a vaginal ITV with daily image guidance ensures accurate daily treatment delivery, added Erickson, noting that systemic chemotherapy should be effectively sequenced with radiation therapy in patients with high-risk histologies of all stages and in FIGO Stage III-IVA disease of all histologies to decrease distant and locoregional recurrence, respectively.
“Sentinel lymph node mapping with pathologic ultrastaging improves the accuracy of surgical staging and results in less morbidity than pelvic lymphadenectomy. Adjuvant therapy should be recommended based on the clinical and uterine risk factors, performance of a nodal assessment, and results of that nodal assessment,” Erickson concluded. “For patients with endometrial cancer considering adjuvant therapy, molecular profiling is recommended and may be used to guide adjuvant therapy.”
Mark McGraw is a contributing writer.