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Few randomized studies exist examining the treatment regimens of recurrent cancers. GOG 238 is a prospective randomized trial evaluating the role of radiation therapy (RT) versus chemoradiation in the management of locally recurrent endometrial cancers.

In this trial, reported in the and conducted between 2008 and 2020, patients with vaginal or pelvic lymph node recurrent endometrial cancers were randomized to either RT or RT plus weekly cisplatin. RT was delivered to the whole pelvis to 45 Gy followed by a boost with either brachytherapy or further external-beam RT to a minimum total dose of 65 Gy. Brachytherapy was delivered using a volumetric approach, with about 60% of patients in both arms receiving high-dose-rate brachytherapy. Cisplatin was delivered weekly at 40 mg/m², extrapolated from its use in other gynecologic malignancies. The primary endpoint was progression-free survival (PFS) as determined from study entry.

A total of 156 patients were evaluated, with 86% having a vaginal recurrence and a median follow-up of 62 months. Not surprisingly, toxicities were higher in the chemoRT arm compared with the RT-alone arm. Median PFS was 73.7 months in the chemoRT arm and was not reached in the RT-alone arm.

There were 13 cancer-related deaths in the chemoRT arm and 7 in the RT-alone arm. Overall survival was 97 months in the RT-only arm and 99.6 months in the chemoRT arm. No clinical factors were found to be associated with PFS.

Patients in this study had significantly better outcomes than those historically treated with a 3-year PFS rate of 73%. The patients included in this study tended to have lower-grade recurrent tumors, and there were likely some enrollment biases in that patients with larger recurrences were not felt to be safe to get radiation alone.

Modern brachytherapy techniques were utilized, which likely contributed to the improved local control seen in patients. Based on these data, the authors suggest that for patients with smaller-volume, low-grade recurrences, radiation alone is the treatment paradigm of choice.

Recent studies have also shown an improvement in outcomes of advanced/recurrent endometrial cancers with the addition of immunotherapy to chemotherapy. Like many cancers, the decision now is how to incorporate two separate sets of data to determine a personalized approach for each patient.

Molecular subtyping of endometrial cancers may continue to help determine the best approach for each patient and help to stratify patients into different paradigms. Until molecular subtyping is widely adopted and approved by insurance, these data provide sound evidence to treat smaller, recurrent tumors with RT alone.

Elizabeth Nichols, MD, is Associate Professor and Vice Chair of Clinical Operations at the University of Maryland School of Medicine, Department of Radiation Oncology, University of Maryland Medical Center, Maryland Proton Treatment Center, in Baltimore.

Read the study here and an interview about it here.