Improved Outcomes with Adjuvant Radiation Therapy in Early-Stage Endometrial Cancer with Abnormal Beta-Catenin Expression

Abstract

<h3>Purpose/Objective(s)</h3> There is increasing data about the prognostic significance of molecular profiling for endometrial cancer outcomes and emerging data showing that abnormal (nuclear) β-catenin expression is associated with an increased risk of recurrence and poorer clinical outcomes. Our study aimed to determine if the addition of adjuvant radiation therapy following surgery improves local control in early-stage endometrial cancer patients with abnormal β-catenin expression. <h3>Materials/Methods</h3> We identified 217 patients with FIGO 2009 stage I and stage II endometrial cancer who underwent surgical resection from 2018 to 2021 at our institution and had molecular data available. We reviewed the β-catenin expression status and outcomes in these patients. Vaginal cuff recurrences, regional recurrences, and distant metastases were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier. <h3>Results</h3> The median follow up time was 22.5 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. Abnormal β-catenin expression was present in 36.8% of all patients (47% of grade 1-2 versus 17% of grade 3 patients (p=0.007)) and associated with no specific molecular profile subtype. Abnormal β-catenin expression was significantly associated with increased rates of vaginal cuff recurrence (<i>p</i>=0.02), was borderline associated with worse overall survival (<i>p</i>=0.07), and not significantly associated with regional recurrence or distant metastases. One third of patients received adjuvant radiation therapy, generally based on other pathologic factors, and radiation was significantly associated with decreased vaginal cuff recurrences in patients with abnormal β-catenin expression (<i>p</i>=0.01). This decreased incidence of vaginal recurrence was seen with the use of any type of radiation including brachytherapy or external beam radiation therapy. <h3>Conclusion</h3> Patients with Stage I-II endometrial cancer with abnormal β-catenin expression have increased rates of vaginal cuff recurrences, and adjuvant radiation therapy in this group significantly improved local control. Radiation therapy should be considered in patients with endometrial cancers demonstrating abnormal β-catenin expression to decrease the risk of vaginal cuff recurrences.