Top Line: What are the long-term outcomes of PORTEC-3 based on molecular classification?
The Study: PORTEC-3 was a phase 3 trial that randomized 660 patients with high risk endometrial cancer to adjuvant radiation or chemoradiation. High risk was defined as: “FIGO 2009 stage I, grade 3, with deep myometrial invasion and/or lymphovascular space invasion; stage II–III; or stage I–III with serous or clear-cell histology.” Chemoradiation significantly improved failure free survival, and a later post-hoc survival analysis found improved overall survival. Since those outcomes, endometrial cancer has been classified into four molecular subgroups: POLEmut, MMRd, NSMP (nonspecific), and p53abn. 10-year outcomes from PORTEC-3 show a continued improvement in OS (74.4% v 67.3%) and RFS (72.8% v 67.4%) with the addition of chemotherapy to radiation. Survival breakdown by molecular subgroup was: POLEmut 98%, NSMP 77.9%, MMRd 71.7%, and p53abn 45.1%. The latter group saw the most significant improvement in OS with the addition of chemotherapy (52.7% v 36.6%). Most serous cancer (74%) were p53abn, and nearly half of p53abn cancers were serous histology. A notable finding was relatively poor outcomes among a small subset of ER-negative NSMP tumors suggesting they may benefit from more aggressive therapy.
TBL: Chemoradiation maintained long-term improvement in OS in PORTEC-3 particularly among those in the p53abn molecular subgroup. | Post, Lancet Oncol 2025
The Study: PORTEC-3 was a phase 3 trial that randomized 660 patients with high risk endometrial cancer to adjuvant radiation or chemoradiation. High risk was defined as: “FIGO 2009 stage I, grade 3, with deep myometrial invasion and/or lymphovascular space invasion; stage II–III; or stage I–III with serous or clear-cell histology.” Chemoradiation significantly improved failure free survival, and a later post-hoc survival analysis found improved overall survival. Since those outcomes, endometrial cancer has been classified into four molecular subgroups: POLEmut, MMRd, NSMP (nonspecific), and p53abn. 10-year outcomes from PORTEC-3 show a continued improvement in OS (74.4% v 67.3%) and RFS (72.8% v 67.4%) with the addition of chemotherapy to radiation. Survival breakdown by molecular subgroup was: POLEmut 98%, NSMP 77.9%, MMRd 71.7%, and p53abn 45.1%. The latter group saw the most significant improvement in OS with the addition of chemotherapy (52.7% v 36.6%). Most serous cancer (74%) were p53abn, and nearly half of p53abn cancers were serous histology. A notable finding was relatively poor outcomes among a small subset of ER-negative NSMP tumors suggesting they may benefit from more aggressive therapy.
TBL: Chemoradiation maintained long-term improvement in OS in PORTEC-3 particularly among those in the p53abn molecular subgroup. | Post, Lancet Oncol 2025