Association of Neoadjuvant Chemotherapy With Overall Survival in Women With Metastatic Endometrial Cancer
Authors: Claire J. Tobias, Ling Chen, Alexander Melamed, Caryn St Clair, Fady Khoury-Collado, Ana I. Tergas, June Y. Hou, Chin Hur, Cande V. Ananth, Alfred I. Neugut, Dawn L. Hershman, Jason D. Wright
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Although primary debulking surgery (PDS) is often considered the criterion standard for treatment of stage IV endometrial cancer, PDS is associated with significant morbidity and poor survival. Neoadjuvant chemotherapy (NACT) has been proposed as an alternative treatment strategy. <h3>Objective</h3> To determine the use of and outcomes associated with NACT for women with stage IV endometrial cancer. <h3>Design, Setting, and Participants</h3> This cohort study used the National Cancer Database to identify women with stage IV endometrial cancer treated from January 1, 2010, to December 31, 2015. The cohort was limited to women aged 70 years or younger with minimal comorbidity (comorbidity score = 0). Women were stratified based on receipt of NACT or PDS. A propensity score analysis with inverse probability weighting was performed to balance the clinical characteristics of the groups. Survival was examined using flexible parametric Royston-Parmer models to account for time-varying hazards associated with use of NACT. An intention-to-treat (ITT) analysis was performed, as was a per-protocol (PP) analysis that included only women who received treatment with both chemotherapy and surgery (in either sequence). Data were analyzed from March 15, 2018, to July 20, 2018. <h3>Main Outcomes and Measures</h3> Use of NACT and overall survival. <h3>Results</h3> Of a total of 4890 women (median age, 60 years [interquartile range, 54-65 years]) with stage IV endometrial cancer, NACT was used in 952 women (19.5%). Use of NACT increased from 106 of 661 women (16.0%; 95% CI, 13.2%-18.8%) in 2010 to 224 of 938 women (23.9%; 95% CI, 21.2%-26.6%) in 2015 (<i>P</i> &lt; .001). In a multivariate model, more recent year of diagnosis (risk ratio [RR], 1.42; 95% CI, 1.21-1.79 for 2015 vs 2010), stage IVB disease (RR, 1.31; 95% CI, 1.03-1.67 for stage IVB vs IVA), and serous histology (RR, 1.38; 95% CI, 1.13-1.69 for serous vs endometrioid histology) were associated with use of NACT. In a propensity score–balanced cohort, use of NACT displayed a time-varying association with survival. In the ITT analysis, use of NACT was associated with decreased mortality for the first 3 months after diagnosis (hazard ratio [HR] at 2 months, 0.81; 95% CI, 0.66-0.99). After 4 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 6 months, 1.23; 95% CI, 1.09-1.39). In the PP analysis, use of NACT was associated with decreased mortality for the first 8 months after diagnosis (HR at 6 months, 0.79; 95% CI, 0.63-0.98). After 9 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 12 months, 1.22; 95% CI, 1.04-1.43). <h3>Conclusions and Relevance</h3> The results of this cohort study suggest that women treated with PDS are at increased risk of early death but have a more favorable long-term prognosis. In contrast, results suggest that women treated with NACT, particularly if they ultimately undergo surgery, may have superior survival in the short term. Based on these findings, NACT may be appropriate for select patients with advanced uterine serous carcinoma.