How should molecular studies, in particular the presence of POLE or p53 mutations, be incorporated into the decision to treat an "intermediate risk" endometrial cancer patient with adjuvant therapy after hysterectomy?  

PORTEC, ESMO, and SGO guidelines support molecular characterization of endometrial cancer based on the TCGA/ProMisE classifications. p53 is a predictive biomarker for response and prognosis while POLE is prognostic. Based on the most recent SGO clinical practice statement, these can be used to escal...

Presence of POLE-Exonuclease Domain Mutation = no adjuvant therapy. Presence of p53 mutation = chemotherapy.

In the absence of true prospective evidence for molecular marker directed therapies, the best approach is to enroll these patients in the several open ongoing clinical trials looking at these molecular features.

We treat G3 endometrioid with p53 mutation similar to serous carcinoma, so would recommend chemotherapy. EBRT or VCB based on primary tumor pathologic factors. I am loath to start de-escalating adjuvant therapy in HIR POLe mutated patients in the absence of prospective data that observing these pat...

Outside clinical trials, favor chemo plus radiation for now based on the European guidelines. 

I recommend systemic chemotherapy with external beam whole pelvic XRT and vaginal brachy therapy because the chances of metastasis are higher and XRT will reduce local recurrence.