If a patient has early-stage grade 1 or 2 endometrioid cancer and high-risk factors such as deep myometrial invasion or cervical involvement, I typically use vaginal cuff brachytherapy. For a patient with early-stage, grade 3, node-negative endometrial cancer, vaginal cuff brachytherapy can also reduce the risk of local recurrence. The question is: Should we give these patients vaginal cuff brachytherapy alone, vaginal cuff brachytherapy with chemotherapy, or even, potentially, vaginal cuff brachytherapy with immunotherapy? This is currently being evaluated in clinical trials.

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Radiation therapy is also discussed with patients who have node-positive disease. However, the GOG-258 trial comparing chemotherapy with or without radiation in patients with advanced disease did not report a survival benefit, but there may have been a benefit in local disease control or in preventing pelvic recurrence. Traditionally, we treated all patients with node-positive disease with chemoradiation followed by chemotherapy. In patients with higher-risk subtypes, in whom we need to prioritize chemotherapy, we may consider 6 cycles of chemotherapy and then reassess for the role of consolidative radiation therapy. If a patient has a mismatch repair–deficient disease, I take radiation therapy off the table because chemotherapy plus immunotherapy improves survival.

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The treatment for endometrial cancer continues to evolve. At least for now, our group at The University of Texas MD Anderson Cancer Center still offers radiation therapy to patients who have node-positive, completely resected disease, particularly those with endometrioid histology. Although the role of pelvic radiation therapy has decreased significantly, I still consider it for these patients because their risk of local recurrence is so high.

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Dr Backes, Dr Penson, and I have the benefit of working at large centers that have gynecology-specific radiation oncologists, but this is not universal, and there are places that do not routinely perform vaginal cuff brachytherapy and have to refer patients to another center. When making treatment decisions, it is important to consider your practice setting and local resources.

I am also using much less radiation therapy. In my practice, vaginal cuff brachytherapy has replaced the use of pelvic radiation therapy for a lot of patients and is something that I consider for those with high-intermediate-risk disease. Patients with deep myometrial or cervical invasion are at a much higher risk for pelvic recurrence, so, for these individuals, I consider pelvic radiation.

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In terms of salvage radiation therapy, I find that small vaginal recurrences can be salvaged fairly easily. Larger recurrences require more treatment, and I sometimes consider a combination of surgery, radiation therapy, and, in some circumstances, chemotherapy. Unlike in cervical cancer, in which cisplatin is used as a radiosensitizer, radiation alone is just as effective for recurrent endometrial cancer confined to the pelvis.

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I typically give chemotherapy to patients with metastatic pelvic-confined disease (eg, stage IIIC1) because of their high risk for distant and pelvic recurrences, and, while radiation therapy can help reduce the incidence of pelvic recurrence, it cannot prevent distant recurrence. I would still consider adding radiation for patients with a bulky uterine carcinosarcoma.

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Even though clinical trials did not find a survival benefit with the addition of radiation therapy to chemotherapy, it is still a consideration for locoregional control, especially for patients who have bulky lymph nodes. There has been a lot of discussion on the national level about a recent exploratory analysis of the GOG-258 study based on molecular classification. It is important to remember that this was an unplanned analysis, but it did suggest a potential benefit of radiation in patients with TP53 wild-type, no specific mutational profile (NSMP) tumors. Based on these results, some people are considering radiation for mismatch repair–proficient disease with NSMP.

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Although most advanced-stage endometrial cancer trials administered radiation followed by chemotherapy, more recent trials, such as KEYNOTE-B21, are giving chemotherapy first with the option of giving radiation therapy after. This has been the way in which we most commonly sequence chemotherapy and radiation at The Ohio State University. In most instances, I also give patients with endometrial cancer chemotherapy first, and then I consider giving them radiation.

Radiation therapy is an essential part of treatment for patients with high-risk endometrial cancer to minimize the chance of local recurrence. We typically use external beam radiation therapy when there are positive nodes and vaginal cuff brachytherapy when there are other risk factors for local recurrence.

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How do we integrate chemotherapy and immunotherapy with radiation therapy to ensure the best outcomes for patients? I think that the advantages we are seeing with the use of ICIs among all-comers in clinical trials encourage their integration into therapy. It is not clear whether the concurrent irradiation of nodes when receiving ICIs is good (ie, benefiting from an abscopal effect) or bad (ie, damaging the very T cells you are trying to educate about the tumor), and creative strategies may help us reach for the best outcomes for our patients. However, they need to be done in a well-informed, carefully considered way in rigorous trials.