Neoadjuvant Chemotherapy Versus Primary Cytoreductive Surgery for Metastatic Endometrial Cancer

To evaluate the pattern of use and clinical outcomes associated with neoadjuvant chemotherapy (NACT) compared with primary debulking surgery (PDS) in patients with stage IV endometrial cancer.

We utilized the National Cancer Database to identify individuals diagnosed with stage IV endometrial cancer, and categorized them according to receipt of NACT or PDS. Propensity score weighting using inverse probability of treatment weighting was applied. Survival outcomes were evaluated using both an intention-to-treat (ITT) analysis, which included all eligible patients, and a per-protocol (PP) analysis restricted to those who underwent chemotherapy and surgery.

Among 18,205 patients, NACT utilization rose from 30.3% in 2010 to 73.8% in 2021 (p < 0.0001). In the multivariable analysis, patients diagnosed in more recent years, Black and Hispanic race and ethnicity, Medicaid insurance, serous histology, and greater comorbidities were associated with NACT (p < 0.05). In the ITT analysis, there was no mortality difference within 4 months after diagnosis between NACT patients and PDS patients (aHR = 1.03; 95% CI: 0.96-1.11); however, after 4 months, patients treated with NACT experienced higher mortality than those undergoing PDS (aHR = 1.58; 95% CI: 1.51-1.64). In the PP analysis, NACT patients had lower mortality compared to PDS patients within 24 months after diagnosis (aHR = 0.93; 95% CI, 0.88-0.99) but a 34% higher mortality after 24 months (aHR = 1.34; 95% CI, 1.23-1.47).

Utilization of NACT has expanded among patients with metastatic endometrial cancer. Primary debulking surgery with postoperative chemotherapy is linked to higher early mortality but improved long-term outcomes relative to treatment strategies beginning with NACT followed by surgery.