Objective To evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy.
Methods Retrospective review identified 62 patients with stage I–II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and image-guided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months follow-up. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan–Meier. Univariate and multivariate analyses were performed by Cox proportional hazards.
Results Most patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3–167), 3- and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with non-endometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1–2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively.
Conclusion Definitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1–2 disease.
- endometrial neoplasms
- neoplasm recurrence
Data availability statement
Deidentified patient data are available upon request to the corresponding author and by approval of the local IRB through a data-sharing agreement.
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Contributors GA and LL were responsible for data collection, analysis, and drafting of the manuscript. JA, IB, MK, JP, and LS provided input on the analysis, presentation of the findings, and manuscript editing.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests LL is the principal investigator of an investigator-initiated clinical trial sponsored by AstraZeneca, has received nonfinancial support from AstraZeneca for sponsored travel, and grant support from the Koch Institute at the Massachusetts Institute of Technology. LS receives research funding from Viewray, outside the scope of this work.
Provenance and peer review Not commissioned; externally peer reviewed.