CHAPTER 3 58 Outcome For the independent variables in cox-regression models the proportional hazard assumption was checked. Results of testing the proportional hazard assumption shows that all the variables were satisfied. The 5-years DSS of the included study cohort showed worst prognosis for TP53-mutant and best for POLE-mutant tumors (Figure 2A). Across all molecular subgroups, patients with low-grade EC had an outstanding 5-year DSS when compared to high-grade EC, varying between 90-100% vs. 41-90% (P<.001), respectively (Figure 2B). For all the molecular subgroups and patients with grade 1 EC, an excellent 5-year DSS is shown (Figure 2C). Patients with grade 2 EC and TP53-mutant or NSMP shows a 5-year DSS of 85-95%, respectively (Figure 2D). Within the external validation cohort (n=373), survival outcomes were similarly distributed across all the molecular subgroups, with 5-year DSS varying between 98-100% in low-grade EC and 62-100% in high-grade EC (P=0.017) (Efigure 2 in the Supplement). In multivariable analysis of the entire cohort, high-grade EC, TP53-mutant and FIGO advanced-stage were independently associated with reduced DSS. Among patients with lowgrade EC, FIGO advanced stage was independently associated with a reduced DSS, but none of the molecular subgroups. However, the number of events was low and the estimated HR’s were of similar magnitude as in the entire cohort (Table 2). Within patients with high-grade EC, only FIGO advanced-stage remained associated as independent prognostic factor for a reduced DSS (Etable 3 in the Supplement).
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