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The addition of chemotherapy did not extend progression-free survival (PFS) for patients treated with definitive radiation therapy for recurrent endometrial cancer, and also increased acute toxicity, researchers reported in the .

Radiation therapy is considered curative for patients with endometrial cancer recurrences confined to the pelvis, with long-term survival rates of 50-70%. The question of whether chemotherapy would increase the survival rate was tested in a study by Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

Klopp, director of Brachytherapy, who also leads the gynecologic section in the Department of Radiation Oncology, elaborated on the results in the following interview.

What does the study add to the literature?

Klopp: This study demonstrated that adding cisplatin to the standard regimen with radiation didn't improve outcomes for these women. Cisplatin has been shown to be effective at improving outcomes for women with cervical cancer and head and neck cancers, so we wanted to see if the same benefits were observed. We didn't find any evidence that outcomes were improved by cisplatin for women with endometrial cancer.

Notably, our study included a particular subset of women with endometrial cancer recurrences -- specifically those with recurrences in the vagina and lymph nodes. We primarily enrolled low- and moderate-grade endometrioid cancers, which were restricted to the vaginal apex. This means that the study results are most applicable to these patients -- that is, it may not be true that cisplatin doesn't provide additional benefit for other types of pelvic recurrences, such as high-grade cancers that extensively involve the lymph nodes.

The majority of patients had low-grade (grades 1 or 2) endometrioid histology (82% of the group) and recurrences confined to the vagina (86%). External-beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam.

Patients randomly assigned to receive chemotherapy were treated with once-weekly cisplatin at 40 mg/m². Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation -- median PFS was not reached for radiation therapy versus 73 months for chemoradiation, hazard ratio of 1.25.

At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression.

One of the important highlights is that endometrial cancer recurrences are so curable when detected early and treated appropriately with radiation. Often recurrent cancers are thought of as incurable, but this is clearly not the case for locally recurrent endometrial cancer. Three-quarters of women were free of progression 3 years after treatment for recurrence.

Which endometrial cancer patients should be treated with radiation therapy without the addition of chemotherapy?

Klopp: Women with pelvic recurrences of endometrial cancer, especially those with low grade tumors.

If recurrences aren't detected early, they may become larger and thus more challenging to treat curatively with radiation therapy. The brachytherapy technique that we use to escalate dose can result in a higher rate of toxicity or a lower rate of controlling tumors if they are large. If recurrences are detected after they have metastasized, they may no longer be curable and would instead be treated with chemotherapy and immunotherapy.

While these drugs may be effective for a period of time, patients often develop resistant disease.

What are the advantages of using image-guided brachytherapy?

Klopp: Image-guided brachytherapy refers to the use of imaging, usually CT or MRI, to define the tumor that is being treated. This ensures that the radiation applied is optimally positioned within or against tumors. Image guidance also helps to evaluate the dose to the tumor as well as ensure that safe radiation doses are delivered to the bladder and bowel. These organs are typically close to the recurrent tumor and limiting the dose has been shown to reduce the risk of short- and long-term toxicities.

What should future research focus on?

Klopp: We may be able to further improve outcomes by combining radiation with radiosensitizing drugs, such as immunotherapy or PARP inhibitors. The ideal combinations will improve tumor response and survival rates while not contributing to the risk of side effects.

What is your main message for practicing oncologists?

Klopp: Based on these data, patients with vaginal-only recurrences of grade 1 or 2 endometrioid endometrial cancer should be treated with radiation therapy without the addition of chemotherapy.

It is important for patients with a history of endometrial cancer to undergo regular exams and investigate any symptoms of vaginal bleeding. Periodic imaging may be recommended to detect nodal recurrences, especially for patients with a high risk of pelvic recurrence.

Read the study here and expert commentary about it here.