Executive Summary of the American Radium Society (ARS) Appropriate Use Criteria (AUC) for Management of Locally...

Locally advanced endometrial cancers are heterogeneous and challenging to treat. Immunotherapy has transformed the treatment landscape. Given the complexity of tailoring adjuvant treatment recommendations, the multidisciplinary American Radium Society Gynecologic Cancer Panel created evidence-based guidelines for the management of locally advanced endometrial adenocarcinoma.

Search terms, key questions, and associated clinical case variants were formed by panel consensus. A review of the literature was conducted from January 1, 1996, to March 5, 2024, using the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines to systematically search the PubMed, Embase, and Web of Science databases to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures.

Evidence for key questions in advanced-stage endometrial cancer was examined. Two rounds of voting were completed pertaining to the appropriateness of key management decisions for 4 clinical variants. Optimal adjuvant treatment is based on pathologic and molecular risk factors, and typically consists of combined modality therapy, with both chemotherapy and radiation, to minimize the risk of local and distant recurrence; there are no prospective data on optimal sequencing. Molecular data from PORTEC-3 highlights that adding chemotherapy to radiation is especially crucial for p53 abnormal tumors. Inclusion criteria for the NRG-GY018/RUBY trials can guide appropriateness of incorporating immunotherapy, which should be considered especially in mismatch repair-deficient (dMMR) patients. Radiation fields should be extended to include para-aortic lymph nodes in IIIC2 disease. Within pelvic radiation, intensity modulated radiation therapy is the preferred technique to mitigate toxicity as supported by prospective data.

Selecting appropriate adjuvant therapies for advanced-stage endometrial cancer is nuanced. Further prospective studies harnessing molecular markers as therapeutic targets will help advance and optimize therapies for more personalized treatment of this complex disease.