Because POLE testing often requires a send-out NGS test, the turnaround time is slow. Clinicians report they cannot wait for these results and must make treatment decisions, such as starting chemotherapy for a p53-mutant tumor, before the full molecular profile, including the crucial POLE status, is known.
When considering escalating therapy for a patient with a high-risk p53 mutation, clinicians are adopting a key checkpoint: confirming the absence of a concurrent POLE mutation. The presence of a POLE mutation is thought to mitigate the aggressiveness of p53-mutated tumors, potentially making treatment escalation unnecessary.
Due to a shortage of genetic counselors and patient access issues, the traditional referral workflow is being inverted. Oncologists now frequently order genetic tests themselves and then refer patients with positive findings to a counselor. This pragmatic shift ensures testing isn't missed due to scheduling delays or patient travel burdens.
To avoid the inefficiency of re-requesting tests, some hospital labs now run a full panel of biomarkers (MMR, p53, HER2) on all endometrial cancer cases upfront. This operational decision standardizes the process, even if not every marker is immediately relevant for all histologies, preventing downstream delays and extra work for pathologists.
To preserve treatment options, oncologists employ a tactical approach to re-testing. They avoid re-biopsying a tumor with a known positive biomarker to prevent a negative result from jeopardizing drug coverage. Conversely, they are more likely to re-biopsy a previously negative tumor at recurrence, hoping to find a new, actionable mutation.
Clinicians are struggling to implement the new FIGO 2023 molecular staging for endometrial cancer. While prognostically significant, it reclassifies patients (e.g., from Stage 1 to 2C) without clear, validated evidence on how to alter treatment based on the new stage. This gap between staging and evidence-based action creates clinical uncertainty.
Following the Keynote B21 trial, clinicians have become more selective with adjuvant immunotherapy in endometrial cancer. The study showed minimal benefit for pMMR patients and less impressive gains overall in its lower-risk population compared to advanced disease trials. This has led to a practice of reserving adjuvant chemo-IO primarily for stage 3 dMMR patients.