Does Charlson Comorbidity Score Dilute the Survival Impact of Adjuvant Radiation Therapy in Women with Early Stage Endometrial Cancer? A Matched Analysis

Abstract

To determine the impact of Age-Adjusted Charlson Comorbidity index (AACCI) score on survival outcomes in women with early stage endometrial cancer using a matched analysis methodology. After institutional review board-approval, 388 women with FIGO stage I-II uterine endometrioid carcinoma were included in this study. 194 women who had received adjuvant radiation treatment (RT) were exactly matched with 194 women who were observed after hysterectomy (1:1 match, strictly based on FIGO stage and grade). AACCI score at time of hysterectomy was determined by trained physicians based on review of all available medical records. Based on AACCI, the study cohort was divided into those with AACCI score of 0 (healthier) vs. those with a score of ≥1. Univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). Median follow-up for the study cohort was 58 months. While women who received adjuvant RT had a significantly higher 5-year RFS (90% vs. 78%, p=0.002), there was no significant difference in 5-year OS (88% vs. 86%, p=0.589). When accounting for comorbidity burden in women who received RT, 5-year OS was (94% vs. 81%, p=0.017) for women with AACCI score of 0 compared to those with a score of > 1, with an absolute difference of 13% at 5-year and 23% at 10 year OS. Similarly, for those who were observed after hysterectomy, 5-year OS was 91% vs 80%, p=0.011. The impact of AACCI was not statistically significant on 5-year RFS and DSS. On multivariate analyses for the entire cohort, higher AACCI score, older age, tumor grade (3 vs 1), and lymphovascular space invasion (LVSI) were significantly independent predictors for shorter OS. LVSI and grade 3 were the only two independent predictors of DSS. The lack of adjuvant RT and the presence of LVSI were significant predictors of worse RFS. Comorbidity burden is just as important as traditional prognostic variables for predicting overall survival in women with early-stage endometrioid endometrial carcinoma. Its prognostic impact should be accounted for in future prospective studies of women with endometrial cancer. On the other hand, its prognostic impact was not observed for RFS and DSS.