Following surgery for intermediate- to high-risk endometrial cancer, clinicians and patients carefully weigh the risks and benefits of adjuvant therapies. Tumor characteristics used to guide treatment selection for advanced and recurrent endometrial cancer may eventually have a role in the selection of adjuvant therapy.

For a cancer like endometrial cancer, for which the initial treatment is typically surgery, I tell patients that there could be some cancer cells remaining after surgery even though we took out all the cancer that we could see and that, unfortunately, the cancer could recur or progress. I explain that our hope with adjuvant therapy is to kill off the remaining cancer cells so that they do not have a chance to regrow.

The problem with adjuvant radiation therapy for endometrial cancer is that it does not impact overall survival (OS). For example, a long-term review of the GOG-99 study reported that the 2-year estimated cumulative incidence of recurrence was reduced from 12% with no additional treatment to 3% with adjuvant radiation therapy, but there was no improvement in OS.

I tell patients that we could potentially reduce the risk of the cancer recurring by approximately 4-fold with adjuvant radiation therapy; however, their life span would likely not be impacted. Some patients will consider this and still decide that they want the adjuvant therapy because they do not want a cancer recurrence, and they like the fact that it significantly reduces this risk. Others feel that they do not want adjuvant therapy if it does not affect how long they will live and because of the potential toxicities.

We should consider adjuvant therapy when we think that it will significantly improve progression-free survival or OS. When speaking with my trainees, I emphasize that we should quantify the risks and benefits of the proposed interventions that may have only a modest benefit in a way that is meaningful for patients. The patient can then make an informed decision through shared decision making.

As an example, going back to the GOG-99 trial, in the high-intermediate–risk group of patients, radiation therapy reduced the risk of recurrence from 27% to 13% and decreased the risk of death from 36% to 17% but increased grade 3/4 toxicity from 6% to 14%. Thus, 100 patients would need to be treated to save 19. These are the types of things that we need to consider in terms of how patients would benefit and how we engage in shared decision making with our patients.

Recent studies have really changed how we determine which patients need therapy after surgery. Historically, the main considerations were the cancer’s histology and stage, and the standard-of-care treatment was the combination of paclitaxel and carboplatin. Over the last 5 years or so, however, a number of studies in the advanced/recurrent setting have suggested that we need to use molecular testing to identify the patients who may benefit from the addition of another therapy to paclitaxel and carboplatin.

So, for example, in patients with advanced/recurrent uterine serous carcinoma that is HER2/neu-positive, there is a benefit when adding trastuzumab to paclitaxel and carboplatin and continuing it as maintenance therapy. In patients with advanced endometrial cancer who have a mismatch repair deficiency, adding immunotherapy or an ICI to paclitaxel and carboplatin and continuing them as maintenance therapy has had a remarkable impact on patients’ progression-free survival. Finally, patients who have TP53-aberrant disease may benefit from bevacizumab, and, based on ongoing clinical trials, those with TP53 wild-type advanced or recurrent endometrial cancer may benefit from maintenance therapy with selinexor. These data suggest that biomarker-driven treatment benefits patients, and this is something that we consider when we look at adjuvant therapy.