National patterns of care and fertility outcomes for reproductive-aged women with endometrial cancer or atypical hyperplasia

Abstract

Background: Although it is uncommon, the incidence of endometrial cancer and atypical hyperplasia among reproductive-aged women is increasing. The fertility outcomes in this population are not well described.

Objective: We aim to describe the patterns of care and fertility outcomes of reproductive-aged women with endometrial cancer or atypical hyperplasia.

Materials and methods: A cohort of women aged ≤45 years with endometrial cancer or atypical hyperplasia diagnosed in 2000 to 2014 were identified in Truven Marketscan, an insurance claims database of commercially insured patients in the United States. Treatment information, including use of progestin therapy, hysterectomy, and assisted fertility services, was identified and collected using a combination of Common Procedural Terminology codes, International Statistical Classification of Diseases and Related Health Problems codes, and National Drug Codes. Pregnancy events were identified from claims data using a similar technique. Patients were categorized as receiving progestin therapy alone, progestin therapy followed by hysterectomy, or standard surgical management with hysterectomy alone. Multivariable logistic regression was performed to assess factors associated with receiving fertility-sparing treatment.

Results: A total of 4007 reproductive-aged patients diagnosed with endometrial cancer or atypical hyperplasia were identified. The majority of these patients (n = 3189; 79.6%) received standard surgical management. Of the 818 patients treated initially with progestins, 397 (48.5%) subsequently underwent hysterectomy, whereas 421 (51.5%) did not. Patients treated with progestin therapy had a lower median age than those who received standard surgical management (median age, 36 vs 41 years; P < .001). The proportion of patients receiving progestin therapy increased significantly over the observation period, with 24.9% treated at least initially with progestin therapy in 2014 (P < .001). Multivariable analysis shows that younger age, a diagnosis of atypical hyperplasia diagnosis rather than endometrial cancer, and diagnosis later in the study period were all associated with a greater likelihood of receiving progestin therapy (P < .0001). Among the 421 patients who received progestin therapy alone, 92 patients (21.8%; 92/421) had 131 pregnancies, including 49 live births for a live birth rate of 11.6%. Among the 397 patients treated with progestin therapy followed by hysterectomy, 25 patients (6.3%; 25/397) had 34 pregnancies with 13 live births. The median age of patients who experienced a live birth following diagnosis during the study period was 36 years (interquartile range, 33-38). The use of some form of assisted fertility services was observed in 15.5% patients who were treated with progestin therapy. Among patients who experienced any pregnancy event following diagnosis, 54% of patients used some form of fertility treatment. For patients who experienced a live birth following diagnosis, 50% of patients received fertility treatment. Median time to live birth following diagnosis was 756 days (interquartile range, 525-1077). Patients treated with progestin therapy were more likely to experience a live birth if they had used assisted fertility services (odds ratio, 5.9; 95% confidence interval, 3.4-10.1; P < .0001).

Conclusion: The number of patients who received fertility-sparing treatment for endometrial cancer or atypical hyperplasia increased over time. However, the proportion of women who experience a live birth following these diagnoses is relatively small.

Keywords: endometrial cancer; endometrial hyperplasia; fertility; fertility conservation; fertility-sparing treatment; health services research; oncofertility.

Figure 1. Cohort identification for reproductive-aged patients with endometrial cancer or atypical hyperplasia

At least 2 outpatient claims or at least 1 inpatient for endometrial cancer [ICD-9-CM 182.0; ICD-10-CM C54.x] or atypical hyperplasia [ICD-9-CM 621.33; ICD-10-CM N85.02] was required for initial study inclusion. Description: Figure 1 depicts the process by which the final analyzed sample was selected from the MarketScan Commercial Database, as well as the rationale and number of patients excluded at different points in the cohort selection.

Figure 2. Reproductive-aged patients with endometrial cancer or atypical hyperplasia receiving progestin therapy

y-axis indicates percentage of patients diagnosed with endometrial cancer or atypical hyperplasia in given year in each treatment group. Patients treated with only hysterectomy are not shown. Fertility-sparing treatment defined as treatment with progestin therapy alone. Patients diagnosed in 1999 not shown due to washout algorithm to exclude prevalent cases. Cases from 2000 not shown as only 22 patients were identified meeting inclusion criteria for analysis; 18% [4/22] received fertility-sparing treatment. Description: Figure 2 depicts a statistically-significant increasing trend in the proportion of patients who were treated with progestin therapy in each subsequent year of the observation period. The total group of patients treated with progestins is divided into those treated with progestin therapy alone [blue] and progestin therapy followed by hysterectomy [orange].