The much anticipated results of PORTEC-3 were recently published in The Lancet Oncology. Stephanie de Boer and colleagues looked to investigate the benefit of adjuvant chemotherapy during and after radiation therapy versus radiation therapy alone for women with high-risk endometrial cancer.
This open-label, randomized phase III trial enrolled a total of 686 women, with 660 eligible patients included in the final analysis. The co-primary endpoints for the study were overall survival and failure-free survival. There was no significant difference in 5-year overall survival between the cohorts. Furthermore, the distant recurrence rate was similar across treatment arms. In a subset analysis exploring failure-free survival, the greatest benefit for combined chemotherapy and radiation appeared to be limited to patients with stage III disease. As anticipated the combined modality arm was associated with greater acute toxicity.
Identifying novel and effective therapeutic regimens in patients with endometrial cancer has been difficult. The rational for systemic therapy exists and is supported by preliminary evidence from earlier trials suggesting a progression-free survival benefit with sequential radiation therapy and chemotherapy. While radiation provides adequate local control, clinicians are commonly anxious about distant disease recurrence. The authors should be applauded for their design and completion of this large prospective trial.
However, as commonly seen in adjuvant trials in endometrial cancer, the patient population is heterogeneous, with early-stage high-risk, and advanced stage disease, potentially diluting a therapeutic effect. In addition, lymphadenectomy was not performed in nearly half of subjects, possibly impacting stage interpretation. Lastly, patients with measurable residual disease were excluded from enrollment on trial, and this population may benefit most from a combinatorial approach.
Future studies may benefit from molecular classification of endometrial cancers, in an effort to better risk stratify subjects, identify relevant prognostic factors, and develop more effective treatment paradigms.