Ashley S. Felix

Adjuvant hormone therapy and overall survival among low-grade and apparent early-stage endometrial stromal sarcoma patients

Surgery is the mainstay of treatment for low-grade endometrial stromal sarcoma (LG-ESS). While adjuvant hormone therapy is recommended for patients with advanced/recurrent disease, no consensus regarding its use among early-stage patients exists. We aimed to identify correlates of adjuvant hormone therapy use and associations of adjuvant hormone therapy and overall survival (OS) in stage I LG-ESS patients. Retrospective cohort study of patients with stage I LG-ESS who underwent hysterectomy from 2004-2019 using data from the National Cancer Database. Categorical data were compared using χ² tests. Kaplan-Meier estimates and log-rank tests were used to compare OS according to adjuvant hormone use. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between adjuvant hormone use and OS were estimated using Cox proportional hazards regression. Of 2,386 patients included, 20.2% were treated with adjuvant hormonal therapy. Use of hormone therapy increased over time, with rates approximately doubling from 2004 to 2019 (12.6% to 24.6%). Age, tumor size, lymphovascular space invasion and adjuvant radiation were associated with adjuvant hormone therapy use. There was no association between adjuvant hormone therapy and OS (log-rank p=0.73; HR=1.05; 95% CI=0.76-1.46) for patients with LG-ESS. Use of adjuvant hormone therapy for stage I LG-ESS has increased over time though is not associated with OS in this cohort of patients. Additional evaluation is needed to understand the impact of adjuvant hormone therapy on recurrence rates, progression rates, and quality of life to fully understand its value.

Management of stage II endometrial cancer and subsequent oncologic outcomes: a National Cancer Database study

The management of stage II endometrial cancer (EC) is challenging due to the wide variation in surgical practice and adjuvant treatment recommendations. We sought to describe the treatment patterns for patients with stage II EC and to evaluate the association between surgical management and adjuvant therapy on survival outcomes in a large cohort of patients with stage II EC. Using data from the National Cancer Database, we identified 9,690 women with stage II EC. We used logistic regression to identify association of sociodemographic and tumor characteristics with surgery type and receipt of adjuvant therapy. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between adjuvant therapy, hysterectomy type, and overall survival. Almost 11% of the cohort underwent radical hysterectomy; however, there was no difference in survival between surgical types even when adjusted for adjuvant therapy (HR=0.94; 95% CI=0.82-1.07). Compared to no adjuvant treatment, radiation only (HR=0.66; 95% CI=0.61-0.73) and combination radiation and chemotherapy (HR=0.53; 95% CI=0.45-0.62) were associated with lower risk of death. There was no survival benefit of chemotherapy alone even when separated by histologic subtype (HR range, 0.55-1.46). Women with stage II EC do not appear to benefit from routine radical hysterectomy though all patients appear to benefit from receipt of radiation therapy (RT), regardless of modality. Additionally, there may be an added survival benefit with the combination of computed tomography and RT in patients with non-endometrioid, high-risk histologies.

Guideline‐concordant endometrial cancer treatment and survival in the Women's Health Initiative Life and Longevity After Cancer study

In the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) cohort, we examined predictors of guideline‐concordant treatment among endometrial cancer (EC) survivors and associations between receipt of guideline‐concordant treatment and survival. Receipt of guideline‐concordant EC treatment was defined according to year‐specific National Comprehensive Cancer Network (NCCN) guidelines. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of guideline‐concordant treatment receipt. We estimated multivariable‐adjusted hazard ratios (HRs) and 95% CIs for relationships between guideline‐concordant treatment and overall survival using Cox proportional hazards regression. We included 629 women with EC, of whom 83.6% (n = 526) received guideline‐concordant treatment. Receipt of guideline‐concordant treatment was less common among women with nonendometrioid histology (OR = 0.24, 95% CI = 0.13–0.45) but was more common among women living in the Midwest (OR = 2.09, 95% CI = 1.06–4.12) or West (OR = 3.02, 95% CI = 1.49–6.13) compared to the Northeast. In Cox regression models adjusted for age, histology and stage, receipt of guideline‐concordant EC treatment was borderline associated with improved overall survival (HR = 0.80, 95% CI = 0.60–1.01) in the overall population. Guideline‐concordant treatment was also linked with better overall survival among women with low‐grade uterine‐confined endometrioid EC or widely metastatic endometrioid EC. Guideline‐concordant treatment varies by some patient characteristics and those women in receipt of guideline‐concordant care had borderline improved survival. Studies evaluating regional differences in treatment along with randomized clinical trials to determine appropriate treatment regimens for women with aggressive tumor characteristics are warranted.

Agreement between Surveillance, Epidemiology, and End Results– and Medicare Claims–Derived Uterine Cancer Treatment Data

Abstract Background: Despite the prevalent use of Surveillance, Epidemiology, and End Results (SEER)–Medicare data to study uterine cancer treatment patterns and survival, concordance between SEER and Medicare claims has not been a focus of prior research. We assessed the agreement between SEER and Medicare claims, predictors of disagreement between sources, and associations between treatment (identified in SEER vs. Medicare) and survival. Methods: Patients diagnosed with uterine cancer between 2000 and 2019 were identified using the SEER–Medicare linked database. We calculated kappa statistics to assess the agreement between the two data sources for receipt of hysterectomy with or without bilateral salpingo-oophorectomy (BSO), hysterectomy with BSO, lymphadenectomy, external beam radiotherapy (EBRT), vaginal brachytherapy (VBT), and chemotherapy. For each treatment type, we examined temporal trends in the kappa and used multivariable-adjusted logistic regression to examine predictors of disagreement. Treatment hazard ratios in Cox proportional hazards regression models using treatment information from SEER versus Medicare were compared. Results: For each treatment, we excluded patients with unknown SEER information, resulting in variable sample sizes. Agreement was lowest for hysterectomy with BSO (kappa = 0.71) and highest for lymphadenectomy and chemotherapy (kappas = 0.85). Temporal variation was evident, with lymphadenectomy, EBRT, and VBT agreement dropping in recent years. Black race, younger age at diagnosis, high-risk histology, and advanced stage were associated with higher odds of disagreement for certain treatments. Associations between treatment identified in SEER versus Medicare and survival outcomes were similar. Conclusions: Treatment agreement between SEER and Medicare was high. Impact: Our results support the use of both data sources for uterine cancer treatment–survival analyses.