The Intricacy and Importance of Treating Inoperable Endometrial Cancer

As the incidence of endometrial cancer is rising, and patients are getting older and more obese, the odds of being faced with a patient who has medially inoperable endometrial cancer have increased. Dominique Rash, MD, FACRO, delivered a presentation at the 2026 American College of Radiation Oncologists (ACRO) Summit, in which she outlined patient cases.

While surgery is always the gold standard of treatment, Rash highlighted that it’s crucial to hold discussions about the necessary treatment for patients who cannot receive surgery. Following the presentation, CancerNetwork® spoke with Rash, a radiation oncologist and an associate professor of Radiation Medicine and Applied Sciences at University of California San Diego, about the importance of this topic.

The conversation covered topics ranging from why this topic, treating inoperable endometrial cancer, was important for a forum like ACRO to how this technique may evolve in the next few years.

Why was your topic important for a forum like the ACRO Summit?

The session organizers were wanting to present some challenging cases with real-world, practical applications for the providers that attend ACRO. Medically inoperable endometrial cancer is probably something that we’re going to be seeing a little bit more of in the future. The incidence of endometrial cancer in the US is rising. Patients are becoming older with additional medical comorbidities and living a longer time. There’s also a cohort of patients who are becoming a little bit more heavyset over time as well, and those are things that increase the probability of being diagnosed with medically inoperable endometrial cancer.

What were the key takeaways?

We tried to prioritize on how best to manage patients with either a combination of external beam radiation with brachytherapy or brachytherapy alone. How do [we] identify which patients benefit from monotherapy with—for example, brachytherapy alone—vs the combined modality therapy? Then, there’s been a lot of discussion of how to incorporate systemic therapy as well, particularly with patients with more advanced stage disease—stage III, stage IV—endometrial cancer.

How do you define “inoperable” endometrial cancer?

There are a couple of ways to identify patients as inoperable. There is medically inoperable, where the surgeon has assessed that the patient is not a good candidate for surgery based on medical reasons, such as other medical comorbidities, the most common of which are cardiovascular and pulmonary disease, or maybe something like higher [body mass index], which can make the minimally invasive laparoscopic procedures much more technically challenging. That contrasts with patients who are inoperable because their disease is too advanced. For example, if you have a uterine cancer that’s extended to the cervix, involving the parametria, or involving a portion of the vagina that cannot be resected, those patients will also be considered inoperable.

In a disease that can change anatomically across treatment, how do you incorporate adaptive planning into your workflow?

One of the major developments over the last 10 to 15 years has been the use of intensity modulated radiation therapy for gynecologic malignancies. The main challenge of which is as you highlight, the organ motion with cervix and uterine cancers, so having good daily, online imaging to verify the patient’s position, not only the external landmarks, but also the internal landmarks, that’s key. Then, with the emerging technologies like adaptive radiotherapy, where you can potentially create an adaptive plan for each daily organ position that is also probably going to go a long way in helping minimize the toxicity of radiation long term, by shrinking down our treatment volumes, it’s not quite ready for prime time. I wouldn’t say that we’re broadly using adaptive radiation for our medically inoperable endometrial cancer patients, but it’s something I consider in select cases.

What patient-centered outcomes, like quality of life, are important to be tracked when treating this disease?

You hit the nail on the head: quality of life. With our patients who are treated with combined external beam [radiotherapy] and brachytherapy, we want to focus on what the urinary toxicity associated with treatment is [and] the [gastrointestinal] toxicity. Then, sexual health is another big one. As you add brachytherapy to external beam [radiotherapy], there is a slightly higher risk of having a detrimental impact on the patient’s sexual function in the long term. Getting patients referred early for physical therapy or other potential interventions to help improve their quality of life is key, especially as we’re starting to see in the more recently published papers that treatment outcomes are getting a little bit better for these patients who have a medically inoperable uterus.

What factors guide your coordination of radiation with systemic therapy in cases where surgery is not feasible?

The stage of the disease at diagnosis, specifically the tumor stage, the nodal stage, if we have somebody who’s got multiple lymph nodes involved, or extensive, bulky tumor that renders them inoperable, we may consider starting with upfront systemic therapy, especially tailoring that systemic therapy based on the molecular profile of the tumor. We know that [mismatch repair (MMR)]-deficient tumors are likely to have as high as 70% to 80% response rates to immunotherapy with cytotoxic chemotherapy. We might start with systemic therapy in those patients and reassess whether they’re operable after that upfront systemic therapy, and then go from there as to whether to treat them with definitive radiation or surgery.

What role do tumor boards and multidisciplinary discussions play in selecting and timing radiation therapy for these patients?

It’s very much an active discussion between the different disciplines that are present at the table. For us, chemotherapy and systemic therapy are also administered by our gynecologic oncologists, so they play the dual role of a surgeon and a medical oncologist in this scenario. We are very much actively discussing these cases to ensure that surgery isn’t a viable option, whether or not you sequence it after systemic therapy or maybe even just after upfront external beam and slightly lower doses of brachytherapy. That could convert somebody who’s otherwise considered unresectable due to the local extent of disease into an operative candidate. We only take surgery off the table when it becomes apparent that there is no way to get good, clear negative margins on a patient, or if they have other comorbidities and their size is not amenable to operative care.

How do you see this technique evolving in the next 3 to 5 years?

Learning how to incorporate the molecular status of these tumors into decisions about adding systemic therapy earlier or even concurrent with definitive radiation is probably going to substantially improve outcomes for us, particularly in those patients who are MMR-deficient, where you know they’re going to respond a little bit better to immunotherapy or immune checkpoint inhibitors. What about adding that on to the definitive radiation? Is that going to improve our outcomes compared with just the definitive radiation alone? Those are open questions that I’m looking forward to seeing the answers to soon.

References

Rash D. Challenging cases: Medically inoperable endometrial cancer. Presented at the 2026 ACRO Summit; February 4-7, 2026; Orlando, FL.