Table 1 Prognostic factors for recurrence in high-risk endometrial cancer.

Recurrence	Pathologic model			Molecular model			Molecular-immune model
N = 378, 111 events	HR	95% CI	p-value	HR	95% CI	p-value	HR	95% CI	p-value
Age	1.05	1.02–1.07	0.00032	1.03	1.00–1.05	0.045	1.03	1.00–1.05	0.034
Adjuvant treatment
RT	reference			reference			reference
CTRT	0.76	0.52–1.10	0.15	0.70	0.48–1.03	0.069	0.72	0.50–1.063	0.093
Histograde
EEC grade 1-2	reference			reference			reference
EEC grade 3	1.24	0.76–2.02	0.40	1.23	0.71–2.14	0.45	1.37	0.79–2.37	0.27
non-EEC	1.42	0.89–2.27	0.14	0.94	0.53–1.70	0.85	1.02	0.57–1.82	0.96
Stage (I-II vs. III)	1.93	1.28–2.91	0.0016	1.90	1.27–2.85	0.0020	1.98	1.31–2.97	0.0011
LVSI	1.25	0.82–1.96	0.30	1.29	0.83–2.00	0.25	1.24	0.80–1.94	0.33
Molecular group
NSMP				reference			reference
POLEmut				no events			no events
MMRd				0.89	0.53–1.48	0.64	0.99	0.59–1.64	0.96
p53abn				2.63	1.46–4.73	0.0012	2.42	1.35–4.32	0.0029
TLS							0.32	0.14–0.73	0.0073

Three Cox proportional hazards models to showing impact of respectively clinicopathological factors, clinicopathological + molecular factors, and clinicopathological + molecular factors + presence of tertiary lymphoid structures on time to recurrence. Covariates were pre-specified according to Léon-Castillo et al. (J Clin Oncol, 2020)². The addition of the molecular classifier to the pathologic model was associated with an improvement in model fit evidenced by: (i) reduction in Akaike’s information criterion (AIC) 1244.968 vs. 1202.158, (ii) increase in model concordance (C index 0.655 vs. 0.714, and (iii) likelihood ratio test for comparison of nested models p = 1.43 × 10⁻¹⁰. Likewise, the addition of TLS presence improved model fit: (i) AIC 1202.158 vs. 1194.242, (ii) C index 0.714 vs. 0.729, (iii) likelihood ratio test for nested models p = 0.0016.
HR Hazard ratio; CI Confidence interval; RT Radiotherapy; CTRT Chemoradiation; EEC Endometrioid endometrial cancer; LVSI Lymphovascular space invasion; NSMP No specific molecular profile; POLEmut Pathogenic polymerase epsilon mutation; MMRd Mismatch repair deficient; p53abn p53 abnormal; TLS Tertiary lymphoid structure.

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