Study Suggests NACT to be Important Treatment Option for Metastatic Endometrial Cancer

Women with metastatic endometrial cancer treated with primary debulking surgery (PDS) are at increased risk of early death, though they also have a more favorable long-term prognosis, according to findings from a cohort study published in JAMA Network Open.

Conversely, the study also indicated that women treated with neoadjuvant chemotherapy (NACT) may experience superior survival in the short term, especially if they eventually undergo surgery.

“These findings suggest that similar to its benefits in ovarian cancer, NACT could potentially lower perioperative morbidity and may serve as an important treatment option among women with metastatic endometrial cancer,” wrote the study authors.

This study employed the National Cancer Database to evaluate women aged 70 years or younger with stage IV endometrial cancer and minimal comorbidity (comorbidity score = 0). Researchers conducted an intention-to-treat (ITT) analysis, as well as a per-protocol analysis which included women who received treatment with both chemotherapy and surgery, in either sequence.

Among 4890 women identified with stage IV endometrial cancer, NACT was used to treat a total of 952 (19.5%). Notably, NACT use 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 (P < .001).

In multivariate analysis, NACT use was associated with 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). Moreover, in a propensity score-balanced cohort, a time-varying correlation with survival was revealed with the use of NACT.

In the ITT analysis, NACT was associated with decreased mortality for the first 3 months following diagnosis (hazard ratio [HR] at 2 months, 0.81; 95% CI, 0.66-0.99). Further, the survival curves crossed after 4 months, and NACT treatment was associated with increased mortality (HR at 6 months, 1.23; 95% CI, 1.09-1.39).

In the per-protocol analysis, NACT use was correlated with decreased mortality for the first 8 months following diagnosis (HR at 6 months, 0.79; 95% CI, 0.63-0.98). After 9 months, the survival curves crossed and NACT receipt was again associated with increased mortality (HR at 12 months, 1.22; 95% CI, 1.04-1.43).

“To our knowledge, there is a paucity of data to date on the use of NACT for the early identification of chemotherapy-resistant disease and resultant patient outcomes. Hypothetically, information regarding response to initial treatment may inform decisions with respect to surgical intervention as well as earlier enrollment in clinical trials, palliative care referrals, and goals of care discussions that have favorable outcomes with regard to quality of life in end-stage disease,” the authors wrote. “Further data exploring the predictive value of response rates to NACT as well as the benefits of NACT in patients felt to have unresectable disease at the time of diagnosis are certainly needed.”

Importantly, a possible limitation of the current study is that the decision to receive chemotherapy versus primary surgery is dependent on both the patient and clinician and is based on a variety of factors that cannot fully be determined using medical records or observational data. In addition, though the National Cancer Database includes women from a number of hospitals, the data may not be representative of the entire population.

Reference:

Tobias CJ, Chen L, Melamed A, et al. Association of Neoadjuvant Chemotherapy With Overall Survival in Women With Metastatic Endometrial Cancer. JAMA Network Open. doi: 10.1001/jamanetworkopen.2020.28612