Dr. Pothuri on the Challenges of POLE Testing in Endometrial Cancer

Bhavana Pothuri, MD, professor, departments of Obstetrics and Gynecology and Medicine, NYU Grossman School of Medicine, director, Gynecologic Oncology Clinical Trials, NYU Langone Health’s Perlmutter Cancer Center, discusses the challenges of DNA polymerase epsilon (POLE) mutation testing in endometrial cancer.

POLE mutation testing requires tissue-based next-generation sequencing, so it can be difficult to test patients with endometrial cancer, Pothuri explains. However, data from several retrospective studies have shown that women with POLE-mutated endometrial cancer have improved recurrence-free survival (RFS) compared with women without the mutation. For example, findings from the phase 3 PORTEC-3 trial (NCT00411138) revealed that women with POLE-mutated high-risk disease had good RFS with chemoradiation, as well as radiation alone.

Moreover, guidelines from ESMO, ESGO, and ESTRO recommend against adjuvant therapy for patients with POLE-mutated stage I and II endometrial cancer, Pothuri explains. Therefore, POLE testing is critical to ensure eligible patients are spared the toxicities of adjuvant treatment regimens.

However, insurance is currently only covering POLE testing for patients with advanced-stage disease, so incorporating the testing into the earlier-stage setting is difficult. Moreover, the retrospective findings need to be validated prospectively before POLE testing can become standard of care for patients with endometrial cancer, Pothuri concludes.