Association of Delayed Adjuvant Therapy and Overall Survival in Early Stage Endometrial Cancer

Abstract

The primary treatment for early stage endometrial cancer includes definitive surgical staging procedure followed by adjuvant therapy in women with high risk of recurrence. The objective of the study is to assess differences in survival according to time interval between surgery and initiation of adjuvant therapy in early stage endometrial cancer. 349,404 patients with primary uterine carcinoma diagnosed from 2004 and 2012 were extracted from National Cancer Database (NCDB). We limited the study population to patients with FIGO 2009 stage I and II endometrial cancer with endometroid, mucinous, clear cell, or serous histology. Adjuvant therapy included radiation therapy, chemotherapy, or a combination. Interval time (IT) was defined as time between surgery and initiation of any type of adjuvant therapy. Patients who died within 90 days post surgery were excluded. We used maximally selected rank statistics to identify an interval time cutoff that generates the most statistically significant difference in overall survival, and Cox proportional hazards model was used to analyze patient characteristics associated with delayed initiation of adjuvant therapy. We identified 117,106 early stage endometrial cancer patients who underwent definitive surgical treatment. Final analysis included 28,647 of 117,106 patients who received some form of adjuvant therapy. Median age was 63 (interquartile range, IQR, 57-71). 10,975 patients (38%) had stage IA disease, 11,153 (39%) patients had stage IB disease, and 6,519 (23%) patients had stage II disease. 13,715 (48%) patients received intra-vaginal brachytherapy alone, 8,996 (31%) patients received pelvic external beam radiation, and 2,098 (7%) patients received a combination of chemotherapy and brachytherapy. The median time from surgery to initiation of adjuvant therapy was 49 days (IQR 40-67 days) and the median follow-up time from start of adjuvant therapy for surviving patients was 49.2 months. Analysis with maximally selected rank statistics revealed an interval time cutoff of 86 days. Interval time shorter than or equal to 86 days was associated with improved overall survival compared to longer than 86 days (Log-rank test p<0.0001). On multivariable analysis, Interval time longer than 86 days compared to shorter or equal to 86 days is independently associated with higher mortality (hazard ratio 1.26, 95% CI 1.15-1.38). Other factors associated worse overall survival included age > 70, serous or clear cell histology, Hispanic race, Medicare/Medicaid as primary payer, facilities located in South and Central U.S. Income level > $63,000 is associated with improved survival. In this large cohort of early stage endometrial cancer patients, interval time between surgery and adjuvant therapy longer than 86 days is associated with significantly increased mortality. Further analysis will be carried to elucidate factors associated with delayed initiation of adjuvant therapy.