Comparison of Adjuvant Radiation Treatment and Chemotherapy Sequencing in Women with Advanced Stage Endometrial Carcinoma

Abstract

There remains no definitive consensus on the optimal sequencing of adjuvant chemotherapy (CT) and radiotherapy (RT) for women with stage III endometrial carcinoma. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) endpoints were compared between women who received RT concurrent with cisplatin followed by 4 more cycles of CT (carboplatin and paclitaxel) and those who received 3 cycles of CT (carboplatin and paclitaxel) then RT alone then 3 more cycles of CT (“sandwich” technique). After IRB approval, we analyzed the data of 140 women with FIGO stage III disease treated from 1/1995 to 12/2017 at our institution. All women were surgically staged and received adjuvant combined modality therapy with different sequences (concurrent or “sandwich”). Differences in variables between the two arms were assessed by chi-squared test. Survival endpoints were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate (MVA) models with Cox regression analyses were generated to determine significant predictors for survival endpoints. Of the 140 women included, 66 (47%) received the “sandwich” technique and 74 (53%) received concurrent therapy. Median follow-up was 43.7 months. There were 77 women (55%) with uterine endometrioid carcinoma and 111 women (80%) with stage IIIC disease. The concurrent group was found to have a significantly better 5-year RFS rate (Hazard Ratio [HR]=0.70, 95% Confidence Interval [CI] 0.46-0.85) compared to the sandwich technique (HR 0.47 [0.33-0.6], p=0.02). There was no statistically significant difference in the pattern of recurrence between the two groups. On MVA, significant predictors of worsened RFS were higher comorbidity burden (Charlson score)(p=0.02), grade 3 vs 2 (p=0.01), FIGO stage IIIC disease (p=0.04), and lower uterine segment involvement (p=0.001). There was no statistically significant difference found between the two groups in regards to OS and DSS. This study suggests that the sequence of radiation therapy given concurrently with chemotherapy is relatively better in terms of recurrence-free survival in women with stage III endometrial carcinoma compared to the “sandwich” approach. These data warrant further validation in a multi-institutional prospective study.