For a patient with IIIC1 (micromets), MSI-high, Grade 2 endometrial adenocarcinoma who has undergone full surgical staging, do you recommend adding immunotherapy to adjuvant chemotherapy + radiation?

Short answer: No, I do not recommend adjuvant CT/IO + RT for this patient based on the patient's risk factors in the prompt, and the data below. Should the patient have recurrent/metastatic disease following adjuvant CT + RT/VCBT, then I/O + CT is a good option. Ongoing trials hope to answer this question (see below).

Data from PORTEC3 or GOG 258 can be used to support adjuvant concomitant chemoradiation. Data from GOG 258 can also be used to support adjuvant CT+VCBT. Data from NSGO/EORTC/MaNGO can be used to support sequential chemotherapy-radiotherapy.

Pembrolizumab + CT is supported for patients with dMMR > pMMR from the NRG-GY018 trial, and ~40% of patients in this study received prior radiation; however, this was not part of the trial...

No.

RUBY only allowed stage IIIC2, any histology, or stage IIIC1 high-risk histology (carcinosarcoma/serous/clear cell) fully resected patients to be enrolled.

NRG-GY018 did not allow any fully resected stage III patient to be included. All stage III patients needed to have unresected gross disease.

KEYNOTE-B21 has been published which now supports the use of immunotherapy in fully resected stage III patients that are dMMR, relevant to this clinical scenario, based on a PFS benefit.

Van Gorp et al., PMID 39284383

Slomovitz et al., PMID 39411812