Matching risk to escalated therapies

Top Line: Little in oncology is more convoluted than the ideal adjuvant treatment for intermediate-risk endometrial cancer.

The Study: The trick isn’t achieving superior oncologic outcomes alone–it’s doing so in a way that minimizes toxicity for those who will do well regardless. This retrospective study of 198 patients receiving post-hysterectomy vaginal brachytherapy for low- (n=90) and high- (n=108) intermediate risk endometrial cancer asks if mismatch repair (MMR) status informs risk of recurrence above and beyond standardly-referenced clinicopathologic features. As expected, patients with MMR-deficient tumors (n=69) were more likely to be high-intermediate risk (65% v 49%), more likely to be high-grade (75% v 57%), and more likely to have lymphovascular invasion (40% v 25%). Nonetheless, on multivariate analysis, deficient MMR status was the standout prognostic variable for recurrence-free survival (HR 3.8). In fact, Figure 1 depicts how MMR status influences local control, completely replacing historic low- versus high- intermediate risk designations (i.e. Kaplan-Meier cures for low- v high-intermediate risk patients with deficient MMR tumors are identical, as are the ones for low- v high-intermediate risk patients with proficient MMR tumors). That is to say, patients with deficient MMR tumors saw a similarly reduced recurrence-free survival at 3 years within both the low- (74% v 100%) and high- (75% v 91%) intermediate risk subgroups.

TBL: The next iteration of trials seeking to clarify which women merit escalated adjuvant therapies for intermediate-risk endometrial cancer should also stratify by MMR-status.