Introduction/Background*The molecular endometrial cancer (EC) classification has proven prognostic impact. However, patients included in previous studies were not always staged by lymphadenectomy (LND) and often received adjuvant treatment (AT). This may have moderated the prognostic effect of the molecular classification. We evaluated the prognostic significance of the molecular classification in high-grade EC patients staged by LND and those without AT.
Methodology Targeted DNA-sequencing for pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynecological Cancer Database 2005-2012 to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Analyses were performed on patients staged by LND and on patients without AT. Time to recurrence analyses were performed using the Kaplan-Meier method, log-rank test and Cox proportional hazard’s models. Pre-specified multivariate regression analyses were performed including age, ASA class, stage, lymphovascular space invasion and in the LND subgroup a propensity score to correct for confounding by indication.
Result(s)*Molecular analysis was successful in 367 EC; 251 patients had undergone LND, see table 1. Median follow-up was 11 years (range 7.5-15.4). Multivariable analysis showed that molecular subgroup was a strong independent prognostic factor for recurrence: p53abn HR 3.88 (95%CI 1.89-7.94, p<0.001) and NSMP HR 4.80 (95%CI 2.14-10.78, p<0.001) compared to MMRd. Figure 1A shows time to recurrence among those patients staged by LND as IA-IB by molecular subgroup.
Among 264 patients without AT, 247 (94%) had stage I-II disease and 17 (6%) stage III. None of the patients with POLEmut EC (n=26, 10%) had a recurrence (figure 1B). Multivariable analysis showed that the significant prognostic impact of molecular subgroup was independent of clinicopathological factors.
Conclusion*The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among patients staged by LND and those without AT. This implies that the unfavourable prognosis of p53abn EC is not caused by undetected lymph node metastasis. POLEmut EC is inherently associated with an excellent prognosis even in the absence of adjuvant treatment.
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