Klopp Comments on Optimizing Chemoradiation in Endometrial Cancer

Ann H. Klopp, MD, PhD

In a debate at the 2018 Society of Gynecologic Oncology Winter Meeting, physicians reviewed the optimal use of adjuvant chemoradiation (CRT) in patients with stage III endometrial cancer, compared with radiotherapy (RT) or chemotherapy (CT) alone.

Ann H. Klopp, MD, PhD, was assigned to defend the use of CRT as the optimal strategy in this patient population. In support of the position, Klopp referred to a retrospective analysis that compared the various treatment approaches.

The analysis included women with node-positive stage IIIC endometrial cancer who were assigned to CRT, RT, or CT. Survival after CRT was superior to no adjuvant therapy (P&#8197;<.001), RT (P&#8197;=&#8197;.010), and CT (P&#8197;<.001). After adjusting for covariates, CRT led to an 83% (P&#8197;<.001) reduction in the risk of death compared with no treatment. The corresponding risk reductions were 62% (P&#8197;=&#8197;.003) and 57% (P&#8197;=&#8197;.024) for CT and RT, respectively.

OncLive: Please provide an overview of your presentation on chemotherapy and radiation in endometrial cancer.What is your opinion on the debate?

In an interview with OncLive at the meeting, Klopp, an associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center, discussed optimizing the use of chemoradiation and the future of the treatment landscape in endometrial cancer.Klopp: A combination of chemotherapy and radiation is the best treatment. The data that we have to support my opinion is from the trial that compared radiation with chemoradiation. It showed improved outcomes with an improvement in disease-free survival when patients had both chemotherapy and radiation. In addition to having better outcomes overall, the combination also reduces the risk of having a recurrence in the pelvis, which is what radiation is particularly useful for.

What challenges are patients likely to experience if they do not receive chemoradiation?

Is there anything else that you would like to add about your presentation?

There is another study that compared chemotherapy with chemoradiation, which showed equivalent survival, but there were more pelvic relapses, which are a symptomatic problem for patients. There was also a quality-of-life effect. My feeling is that the combination is what gives patients the best overall outcomes. For the patients who only receive chemotherapy and do not receive radiation, there is a 30% risk of having the cancer come back in the pelvis. Sometimes those patients can still get curative radiation treatment, but it is a more intensive type of radiation and does not always work. For that reason, preventing that situation for patients who are at high risk is important.It is difficult data to sort through and takes a lot of expertise and effort to churn through these studies. It is a discussion that I am happy to be a part of, especially since it is not an easy answer for everyone, even those of use that spend our time figuring it out on a daily basis.

What does the future treatment landscape of endometrial cancer look like to you?

You mentioned the biology of these tumors and how that helps to determine which treatment to give a patient. Are there any ongoing studies investigating this?

I enjoyed hearing some of the case discussions. It is interesting to hear different physicians’ perspectives on how to approach problems from different institutions in the gynecologic community. As a radiation oncologist, it is not that often that I am in the environment of a different specialty. Going forward, the hope is that we can better distinguish subsets of patients based on their biology who need different types of treatments. For example, some patients may benefit from an immunotherapy regimen, whereas some may benefit from targeted therapy. I would say that our best evidence and the standard of care should be both chemotherapy and radiation. A couple of years ago there was a comprehensive analysis of the molecular biology of endometrial cancer that identified some subgroups. The challenge is designing trials to test the benefit of treatments in those subgroups because once you make smaller groups, it gets hard to design trials that are large enough to answer questions. That is the challenge but there is good evidence that there are molecular subtypes among endometrial cancers.

Binder PS, Kuroki LM, Zhao P, et al. Benefit of combination chemotherapy and radiation stratified by grade of stage IIIC endometrial cancer [published online September 12, 2017]. Gynecol Oncol. doi: 10.1016/j.ygyno.2017.08.031.