Impact of stage and grade on conditional survival in 173,211 women with endometrioid endometrial carcinoma

Abstract

<h3>Objectives:</h3> Survival is often discussed in terms of five-year survival. However, conditional survival expresses the probability of survival as a function of time already survived. The purpose of this study was to investigate the impact of stage and grade on overall survival, conditional survival and relative mortality risk in women with endometrioid endometrial carcinoma (EEC). <h3>Methods:</h3> Eligible participants were diagnosed following surgery with low grade (LG)-EEC (grade 1/2) or high grade (HG)-EEC (grade 3) between 2004 and 2014 in the National Cancer Database. Survival was compared by stage with log-rank test and with multivariate Cox modeling in LG-EEC or HG-EEC. Five-year conditional survival was evaluated by stage using Kaplan-Meier method in women with LG-EEC or HG-EEC who survived 1 to 5 years after diagnosis. Standardized mortality ratio (SMR) defined as the ratio of observed to expected number of deaths was estimated based on the mortality risk of general US population matched by age and race. <h3>Results:</h3> There were 147,944 women with LG-EEC (85.9% stage I, 5.7% stage II, 7.4% stage III, 1.0% stage IV) and 25,267 with HG-EEC (57.4% stage I, 8.7% stage II, 24.7% stage III, 9.3% stage IV). Stage was an independent poor prognostic factor in LG-EEC and HG-EEC (Fig. 1A). Adjusted HR was 1.67, 2.88 and 7.25 for stage II, III and IV vs. I LG-EEC and 1.78, 3.20 and 6.73 for stage II, III and IV vs I HG-EEC, respectively (<i>P<0.0001</i>). Five-year conditional survival for women with stage I, II or III LG-EEC or with stage I HG-EEC changed minimally after surviving at least 1 and up through 5 years (Fig. 1B). In contrast, five-year conditional survival improved in women with stage IV LG-EEC from 48.7% to 58.1% and 69.4% after surviving 2 and 4 years, and in women with stage II HG-EEC from 65.4% to 73.8% and 80.4% after surviving 3 and 5 years, respectively (Fig. 1B). More rapid and incremental improvements in conditional survival occurred after surviving 1, 2, 3 and 5-years for women with either stage III HG-EEC (52.4% to 57.2%, 64.7%, 69.2% and 75.3%) or stage IV HG-EEC (24.9% to 35.7%, 49.2%, 63.4% and 75.0%, respectively (Fig. 1B). SMR represents the age- and race-matched mortality risk of a member in the cohort compared with the general population. The change in SMR over time mirrored the change in conditional survival and dropped from 10.73 to 5.37 in women with stage IV LG-EEC, 4.08 to 2.33 with stage II HG-EEC, 7.34 to 3.27 with stage III HG-EEC and 19.50 to 3.42 with stage IV HG-EEC after surviving 5 years (Fig. 1C). <h3>Conclusions:</h3> Prognosis for EEC improves over time in almost all groups with the most significant improvement in women with advanced stage and high-grade disease. Conditional survival provides clinicians and patients with an informative incremental recalibration in prognosis during the milestones of survivorship advancing shared decision-making across the continuum of care regarding treatment and surveillance.