Impact of Adjuvant Pelvic External Beam Radiotherapy or Vaginal Brachytherapy on Clinical Outcomes for Early-Stage Uterine Carcinosarcoma

Abstract

<h3>Purpose/Objective(s)</h3> Uterine carcinosarcoma (UCS) is an uncommon but aggressive malignancy with poor prognosis. There is no clear consensus regarding adjuvant radiotherapy (RT) following surgical management for patients (pts) with early stage UCS. We compared outcomes for pts with early stage UCS who underwent adjuvant pelvic external beam RT (EBRT) vs. vaginal brachytherapy (VBT) alone. <h3>Materials/Methods</h3> We conducted an Institutional Review Board-approved single institution retrospective study of 98 pts diagnosed with FIGO stage I-II UCS from 2002 to 2020 and received adjuvant RT, with or without chemotherapy (CT), following definitive surgery. EBRT dose was 45-50.4 Gy alone or followed by VBT boost of 10-18 Gy in 2-4 fractions (fx). Dose for adjuvant VBT alone was 21 Gy in 3 fx or 24 Gy in 6 fx, prescribed to the vaginal surface. We recorded clinical and treatment characteristics and clinical outcomes, including dates and location of progression. Fisher exact tests were used for categorical variables. PFS and OS were analyzed by Kaplan-Meier method and log-rank test. Univariate analyses (UVA) were performed using Cox proportional hazards modeling. <h3>Results</h3> 38 received CT+EBRT, 31 received CT+VBT, and 29 received RT alone (18 EBRT, 11 VBT). Fewer pts in the CT+EBRT and RT-alone groups received nodal sampling compared to pts in the CT+VBT group (<i>P</i>=0.02). Other factors including age, comorbidities, FIGO stage, and pathology were not different between the three groups. Median follow up was 93.5, 50.2, and 143.0 months for CT+EBRT, CT+VBT, and RT-alone groups, respectively. 3-year PFS was 78.7%, 67.6%, and 58.2% for CT+EBRT, CT+VBT, and RT alone, respectively. EBRT+CT significantly improved PFS (P=0.01) compared to RT alone (P=0.01), but not compared to CT+VBT (P=0.22). In terms of locoregional recurrences, 1 pt had a vaginal recurrence and 3 had pelvic nodal recurrences after CT+EBRT. In the CT+VBT cohort, 4 pts had vaginal recurrences, 3 had pelvic nodal recurrences, and 1 had a pelvic soft-tissue recurrence. In the RT-alone group, 1 pt receiving VBT suffered a vaginal recurrence, and 4 pts receiving EBRT had pelvic nodal recurrences. UVA showed that compared to CT+EBRT, RT alone was associated with shorter time to progression (HR 2.50, 95% CI 1.08-5.79, <i>P</i>=0.03) but CT+VBT was not (HR 1.82, 95% CI 0.74-4.50, <i>P=</i>0.20). Other factors including age, stage, nodal sampling, and lymphovascular invasion were not significant on UVA. <h3>Conclusion</h3> In one of the largest retrospective cohorts of early stage UCS, we found adjuvant EBRT+CT improved outcomes compared to RT alone, but not CT+VBT. There were 5 vaginal recurrences in pts undergoing VBT, suggesting that VBT alone at the doses prescribed in this study may not be sufficient. Larger prospective studies and longer follow up are needed to further investigate differences in radiation modalities for the treatment of early-stage UCS. †In Memoriam: LJL, deceased June 23, 2021.