IMPORTANCE As the number of young women with early-stage endometrial cancer
is increasing, there is growing interest in use of progesterone-based therapy to allow fertility
preservation.

OBJECTIVE To ascertain the long-term survival of premenopausal women with clinical stage I
endometrial cancer treated primarily with fertility-preserving hormonal therapy compared
with hysterectomy.

DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the National Cancer
Database to identify female patients aged 18 to 49 years with clinical stage I, grade 1 to 2,
endometrioid endometrial cancer diagnosed from 2004 through 2020. In addition, trends
in and factors associated with the use of fertility-preserving hormonal therapy were
examined. Propensity score matching was used to compare survival among patients treated
primarily with fertility-preserving hormonal therapy and those treated with hysterectomy.
Data were analyzed from November 2023 to January 2024.

EXPOSURES Primary treatment was defined as hysterectomy or fertility-preserving hormonal
therapy based on days from diagnosis to operation or fertility-preserving hormonal therapy.

MAIN OUTCOMES AND MEASURES Time to all-cause mortalitywas measured in months from
cancer diagnosis to death or last follow-up at 2-year, 5-year, and 10-year intervals.

RESULTS A total of 15 849 women, including 14 662 (92.5%) treated with primary
hysterectomy (mean [IQR] age, 44 [39-47] years]) and 1187 (7.5%) who received primary
hormonal therapy (mean [IQR] age, 34 [30-38] years) were identified. The use of hormonal
treatment increased from 5.2%in 2004 to 13.8% in 2020 (P < .001). After propensity score
matching, 5-year survival was 98.5%(95%CI, 97.3%-99.2%) for primary hysterectomy and
96.8%(95%CI, 95.3%-97.8%) for primary hormonal therapy (hazard ratio [HR] = 1.84; 95%
CI, 1.06-3.21). Among patients younger than 40 years, there was no difference in survival
between hysterectomy and hormonal therapy (HR = 1.00; 95%CI, 0.50-2.00). However, for
patients aged 40 to 49 years, fertility-preserving hormonal therapy was associated with
a significantly increased risk of death (HR = 4.94; 95%CI, 1.89-12.91).

CONCLUSIONS AND RELEVANCE This study found that the use of fertility-preserving hormonal
therapy among reproductive age patients with early-stage endometrial cancer has increased
over time. While overall survival in patients with hormonal therapy is shorter than with
hysterectomy, survival for patients younger than 40 years of age is comparable after primary
treatment with fertility-preserving hormonal therapy or hysterectomy.