Timing of chemotherapy does not impact survival in advanced-stage endometrial cancer

Abstract

Objectives: The optimal timing of chemotherapy for advanced stage endometrial cancers (EC) is not known. In other advanced gynecologic malignancies, delays in treatment start have been associated with adverse outcomes. We sought to assess whether timing of neo-adjuvant (NACT) and post-operative (POC) chemotherapy in Stage III and IV EC impacts survival. Methods: Patient data from the combined SEER-Medicare database from 1991-2015 was collected. The population included 826 patients with 2009 FIGO III-IV EC who received chemotherapy as first treatment. Patients were categorized by mode of treatment: chemotherapy alone (CT), or chemotherapy with subsequent surgery (CT+S). Patients were further stratified by the time from diagnosis to start of chemotherapy. Using the median time, the four quartiles identified were 0-9 days (Q1), 10-25 days (Q2), 26-45 days (Q3), and 46-301 days (Q4). In the CT+S cohort, the time to POC was assessed. Interaction between race and chemotherapy timing were assessed as well. Multivariable Cox regression models were used to identify treatment factors associated with overall survival (OS) and cause specific survival (CSS). Results: A total of 502 and 324 patients had CT and CT+S respectively. Radiation was given in 32.1% and 45.1% of the patients in the CT and CT+S cohorts respectively, and the addition of radiation was associated with improved survival (OS HR 0.66 [0.55-0.80]; CSS HR 0.64 [0.51-0.80]). The CT+S patients were significantly younger, were more likely to be stage III, of type II histology, and had an earlier time to start of chemotherapy when compared with CT. OS (HR 0.39 [0.33-0.46]) and CSS (HR 0.35 [0.28-0.44]) were significantly improved in the CT+S cohort compared to the CT cohort. In the CT+S cohort, the median time to start NACT was 21 days. When stratifying by quartiles, Q4 was associated with improved survival when compared with Q1 (CSS HR 0.41 [0.21-0.79]), and Q2-Q3 (OS HR 0.61 [0.40-0.93]; CSS HR 0.43 [0.23-0.80]). There was no significant difference found amongst the other quartiles. The median time to start of POC was 32 days. When stratifying by quartiles, timing of POC start was not associated with survival (OS p=0.942; CSS p=0.881). Similarly, in the CT cohort, median time to start NACT was 28 days. Q4 was associated with improved survival when compared with Q1 (OS HR 0.50 [0.38-0.66]; CSS HR 0.50 [0.36-0.69]) and Q2-3 (OS HR 0.62 [0.49-0.77]; CSS HR 0.62 [0.47-0.81]). There were no differences in times to treatment based on race. Conclusions: In patients with advanced stage EC who receive NACT, delays in chemotherapy start both prior to and following interval debulking surgery do not appear to impact survival. These results stand independent of race and demographic features. Interestingly, a majority of the cohort did not undergo hysterectomy and survival outcomes were worse in this group. Timing of treatment initiation did not impact survival, even in this poor prognostic group.