Molecular classification has strong prognostic value in high-risk endometrial cancer and should be incorporated in future trials to target subgroups of patients, according to a molecular analysis of patients in the PORTEC-3 Trial (J Clin Oncol. 2020 Aug 4. Epub ahead of print).

“The randomized (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus radiotherapy alone for women with high-risk endometrial cancer,” wrote Alicia Leon-Castillo, Leiden University Medical Center, the Netherlands, and co-investigators.

Dr Leon-Castillo et al proceeded to investigate prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from trial participants because The Cancer Genome Atlas defined an endometrial cancer classification as a strong prognostic value.

The primary end point was recurrence-free survival (RFS).

A total of 410 high-risk endometrial cancer tissue samples were successfully molecularly analyzed, identifying 4 sub-groups: p53abn (n = 93; 23%), POLEmut (n = 51; 12%), MMRd (n = 137; 33%) and NSMP (n = 129; 32%).

The 5-year RFS rates were 48% in patients with p53abn endometrial cancer, 98% for POLEmut endometrial cancer, 72% for MMRd, and 74% for NSMP endometrial cancer.

For patients with p53abn endometrial cancer, the 5-year RFS rate observed with combined chemotherapy and adjuvant radiotherapy was 59% compared with 36% with radiotherapy alone.

The 5-year RFS rate for chemotherapy with adjuvant radiotherapy versus radiotherapy alone was 100% versus 97%, respectively, for patients with POLEmut endometrial cancer; 68% versus 76% for patients with MMRd endometrial cancer; and 80% versus 68% for patients with NSMP endometrial cancer.

Dr Leon-Castillo et al found that molecular classification has strong prognostic value in high-risk endometrial cancer.

In addition, they noted improved RFS with adjuvant chemotherapy and radiotherapy for p53abn tumors and that in both trial arms, patients with POLEmut endometrial cancer had an excellent RFS.

“[Endometrial cancer] molecular classification should be incorporated in the risk stratification of these patients as well as in future trials to target specific subgroups of patients,” the investigators concluded.—Kaitlyn Manasterski