June 3, 2024
By Catlin Nalley
New data revealed the increasing use of fertility-preserving hormonal therapy among patients with early-stage endometrial cancer who are of reproductive age. Younger age, more recent year of diagnosis, non-White race, lower tumor grade, and earlier stage of disease were all associated with the use of hormonal therapy.
This research was recently presented by study author Yukio Suzuki, MD, PhD, Gynecologist in the Department of Obstetrics and Gynecology at Columbia University Vagelos College of Physicians and Surgeons, during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31-June 4 in Chicago (Abstract 5508).
“The incidence of endometrial cancer is increasing in the U.S. and also globally due to increased obesity rates and prolonged life expectancy,” Suzuki stated. “Endometrial cancer most commonly occurs in postmenopausal women, but approximately 12 percent of newly diagnosed endometrial cancer in the U.S. will occur in premenopausal patients.
“Recent trends toward delayed childbearing predict a growing population of premenopausal patients with early-stage endometrial cancer who may desire fertility preservation,” he continued. “Guidelines offer fertility preservation as an option for premenopausal patients who desire fertility as an alternative to hysterectomy.”
While a substantial proportion of reproductive-age patients achieved a complete response (CR) within the first 12 months with hormonal therapy, there are patients who cannot achieve CR in the primary treatment. This may affect survival outcomes, according to Suzuki, who also noted there is currently a paucity of data on long-term outcomes of hormonal therapy.
To address this knowledge gap, Suzuki and colleagues initiated the current study to better understand the safety and long-term outcomes of hormonal therapy for premenopausal women with early-stage endometrial cancer.
Researchers used the National Cancer Database to identify patients (18-49 years old) with clinical Stage I, Grade 1-2, endometrioid endometrial cancer diagnosed from 2004 to 2020. In this analysis, primary treatment was defined as hysterectomy or hormonal therapy. Key exclusion criteria included the following: discrepancies in AJCC clinical TNM stage, diagnosis not confirmed pathologically, radiation/chemotherapy prior to hysterectomy or hormonal therapy, and unclassified endometrioid cancer.
Suzuki and team evaluated trends in the use of hormonal therapy. They developed a multivariable regression model to examine the association between hormonal therapy and demographic factors. After propensity score matching, survival was compared between patients treated primarily with hormonal therapy and with primary hysterectomy.
The study included a total of 15,849 patients. Of those patients, 14,662 (92.5%) were treated with primary hysterectomy and 1,187 (7.5%) received primary hormonal therapy. Researchers observed an increase in the use of hormonal therapy from 5.2 percent in 2004 to 13.8 percent in 2020. A multivariable model showed that younger age, more recent year of diagnosis, non-White race, lower tumor grade, and earlier stage were associated with the use of hormonal therapy.
“After propensity score balancing, 5-year survival was 98.5 percent (95% CI: 97.3-99.2) for hysterectomy and 96.8 percent (95% CI, 95.3-97.8) for hormonal therapy,” according to the investigators. Among patients <40 years of age, there was no difference in survival between hysterectomy and hormonal therapy (HR=1.00; 95% CI: 0.50-2.00),” they reported. “However, for patients aged 40-49, hormonal therapy was associated with a significantly increased risk of death (HR=4.94; 95% CI: 1.89-12.91).”
In subset analyses stratified by grade (1 or 2) or stage (1A or 1B), Suzuki and colleagues saw no statistically significant difference in outcomes for hormonal therapy when compared to hysterectomy.
During his presentation, Suzuki acknowledged the limitations of this research. “Although we used propensity score matching cohort, we need to pay attention to the existence of unmeasured confounders,” he said. “We were not able to determine the real indication for hormonal therapy. This study has potential selection bias because of the several exclusion criteria. In addition, this is not cancer specific survival.”
Concluding his presentation, Suzuki highlighted the increasing use of fertility-preserving hormonal therapy among reproductive-age patients with early-stage endometrial cancer.
As discussed above, younger age, more recent year of diagnosis, non-White race, lower tumor grade, and earlier disease stage are all correlated with hormonal therapy use. “Overall survivals are similar among women younger than 40 years with primary hysterectomy and primary hormonal therapy from 10-year follow-up,” he said.
“Shared decision-making should be carefully utilized in all patients, particularly in women aged 40-49 with early-stage endometrial cancer given the potentially poorer prognosis associated with initial hormonal therapy,” Suzuki told Oncology Times. “In the next step, we need to identify which patients would be resistant to progesterone-based hormonal therapy based on molecular classification or genetic alteration.”
Catlin Nalley is a contributing writer.