Potent responses to chemo-immunotherapy are promoting a shift toward neoadjuvant treatment for advanced endometrial cancer. Waiting six cycles often achieves a response sufficient to allow for a minimally invasive hysterectomy instead of a more extensive primary debulking surgery.

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.

Even when neoadjuvant immunotherapy achieves an excellent systemic response in MSI-high endometrial cancer, residual disease frequently persists within the uterus. This finding cautions against forgoing hysterectomy based on imaging or systemic response alone.

The future of GYN oncology immunotherapy is diverging. For responsive cancers like endometrial, the focus is on refining biomarkers and overcoming resistance. For historically resistant cancers like ovarian, the strategy shifts to using combinatorial approaches (e.g., CAR-NKs, vaccines) to fundamentally alter the tumor microenvironment itself, making it more receptive to an immune response.

Disparate clinical trial results in endometrial cancer suggest a mechanistic difference between immunotherapy targets. PD-1 inhibitors (dostarlimab, pembrolizumab) have shown pronounced responses, whereas the PD-L1 inhibitor atezolizumab did not, indicating that targeting the PD-1 receptor may be a more robust strategy in GYN cancers.

Early neoadjuvant trials show that while immunotherapy can eliminate metastatic endometrial cancer, residual disease often persists within the uterus. This suggests the uterus is a protected environment, tempering enthusiasm for omitting hysterectomy even in exceptional responders.

Unlike other cancers, re-treating with immunotherapy after recurrence is considered a viable strategy for dMMR endometrial cancer. Experts theorize that these tumors are constantly evolving and may benefit from a "re-education" of the immune system, challenging the conventional wisdom that progression on a drug class means permanent resistance.