What is the Optimal Adjuvant Treatment Sequence for Node-Positive Endometrial Cancer?

Purpose/Objective(s): Adjuvant treatment in women with node-positive endometrial carcinoma (EC) typically consists of chemotherapy (CT) with tumor-directed radiation treatment (RT) delivered sequentially or concurrently. However, the optimal sequence of administering CT and RT remains controversial. We evaluated survival outcomes in women with advanced stage EC across different sequences of adjuvant therapy using the National Cancer Database (NCDB). Purpose/Objective(s): The NCDB was queried for adult females with FIGO 2009 stage IIIC1-IIIC2 EC diagnosed from 2003-2013 treated definitively with hysterectomy, adjuvant CT and RT. Sequence of CT and RT was determined using difference between the time to initiation of CT and RT. Two groups were created: those with CT upfront followed by RT (sequential), and those who received CT and RT concurrently. Therapy was considered concurrent if start days were within 4 weeks. Those with adjuvant therapy delivered later than 6 months from diagnosis were excluded. Chi-square tests were used to assess differences by sequence (sequential or concurrent) and various clinical variables. Log rank test and Cox proportional hazards models were used to evaluate survival outcomes. Risk factors related to overall survival (OS) were identified by univariate and multivariate analyses. Results: Of 1,826 patients that met inclusion criteria, 67% (1,218) received sequential treatment and 33% (608) concurrent treatment. The median follow-up for all patients was 49.2 months. The median age was 61 years and the majority of patients (79%) were stage IIIC1. A brachytherapy boost was used in 34% of all patients. A median of 16 nodes were examined with 2 nodes positive in the sequential group and 14 nodes examined and 2 nodes positive in the concurrent group. Patients treated sequentially had a better 5-year OS (67% [95% confidence interval 64-70%]) than those treated concurrently (62% [57-66%]) (p = 0.004). On multivariate analysis, increasing age (hazard ratio [HR] 1.04 [1.02-1.06], p\u3c.0001), Bokhman type 2 versus type 1 (HR 1.55 [1.04-2.31], p=0.03), grade 3 versus 1 (HR 2.57 [1.26-5.24], p=0.009), and concurrent versus sequential treatment (HR 1.56 [1.09-2.22], p=0.01) were the strongest predictors of worse OS. Conclusion: This large population-based study suggests that about two-thirds of patients with node-positive endometrial carcinoma could be cured with adjuvant multimodality treatment. Upfront CT followed by RT may be a better treatment sequence in this population of patients. Prospective studies addressing this question are warranted