Introduction Determine whether molecular classification using mismatch repair (MMR) and p53 protein expression predictsRFS in EC patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).
Methods GOG-0258 was a phase III, randomized trial (NCT00942357) comparing CRT and CT with primary endpoint of RFS. Immunohistochemistry was performed to determine MMR and p53 status. Demographic variables were compared with chi-squared and Kruskal Wallis tests for categorical and continuous variables, respectively. Kaplan-Meier curves estimated RFS between sub-groups. Adjusted Cox proportional hazards models estimated hazard ratios and 95% confidence limits.
Results Using a modified ProMiSe algorithm, 27.4% of EC classified as dMMR, 49% p53wt, and 23.6% p53abn. p53abn tumors were more frequent in older (p<0.001ADD p-value) and Black (p<0.001ADD p-value) patients, and those with serous histology (p<0.001ADD p-value). In contrast, dMMR was more common in Non-Hispanic patients (ADD p-valuep=0.025) and endometrioid cancers (p<0.001ADD p-value). 5-year RFS was significantly worse for those with p53abn [28.8% vs 68.9% vs 57.5%; HR=3.39 (2.34–4.91); p<0.001] compared to p53wt (referent) and dMMR ECs. After adjusting for age, gross residual disease, and treatment,p53wt was associated with improved RFS in the CRT compared to CT group [77.2% vs 59.7%; HR=0.54 (0.32–0.94); p=0.02]. The 5-year RFS with CRT versus CT were similar for those with p53abn [29.3% vs 29.4%; 0.76 (0.46–1.24)] and dMMR [52.5% vs 63.7% (0.70–2.57)] ECs.
Conclusion/Implications Molecular classification is prognostic in EC, with worse RFS in p53abn tumors. In an exploratory analysis, p53wt appears to be predictive for treatment efficacy favoring CRT over CT. Further trials are warranted to confirm these findings.
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