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.

In metastatic colorectal cancer, clinicians are using ctDNA MRD testing to help guide the decision to stop immunotherapy. For patients who have been on treatment for 1.5-2 years with a complete or durable radiographic response, a negative ctDNA result provides an additional layer of confidence to discontinue therapy.

As various maintenance therapies (immunotherapy, ADCs) are integrated into endometrial cancer treatment, the next major clinical question is defining how long these agents need to be continued to maximize benefit while minimizing long-term toxicity and patient burden.

While chemo plus immunotherapy showed a benefit in MS-stable patients, it's not curative. The expert predicts clinicians may shift away from using it universally upfront, potentially favoring other agents first for this non-curative but beneficial therapy.

Clinicians anecdotally report that immunotherapy is changing the pattern of recurrence in endometrial cancer. Instead of widespread disease, patients often develop isolated recurrences in a single location. This shift allows for the use of local therapies, like radiation, to treat the single spot while continuing the effective systemic immunotherapy.

While immunotherapy is transformational for DMMR endometrial cancer, its benefit is much smaller for the PMMR majority (two-thirds of patients). This reality requires more nuanced patient counseling and selective use in this population.

Despite significant interest, circulating tumor DNA (ctDNA) is not yet an actionable tool for guiding the duration of maintenance immunotherapy in endometrial cancer. While studies like DuoE show ctDNA levels correlate with outcomes, there is no evidence to support using its clearance to decide when to stop treatment. It remains a prognostic, not a predictive, biomarker for this purpose.

For dMMR endometrial cancer patients on combination therapy, clinicians are quicker to reduce or stop chemotherapy (like taxanes) when side effects arise. This practice reflects a growing confidence that immunotherapy is the primary driver of efficacy in this subgroup, allowing for a reduction in chemotherapy-related toxicity.

Clinicians observe that even when immunotherapy leads to a complete response in metastatic endometrial cancer sites, residual disease often persists in the uterus. This suggests the uterine environment is uniquely resistant, making hysterectomy necessary even when a patient appears to be systemically disease-free.