Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients’ information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

Background/Objectives: The treatment-free interval (TFI) predicts benefit from platinum rechallenge in gynecological cancers, but its prognostic value in patients receiving second-line pembrolizumab plus lenvatinib for recurrent endometrial cancer (EC) is unknown. We evaluated whether the TFI is associated with survival and toxicity in this setting. Methods: Using the TriNetX Research Network (122 healthcare organizations, United States and Europe), we identified adults aged 18–90 years with advanced or recurrent EC between January 2018 and June 2026 who received three to six cycles of first-line carboplatin plus paclitaxel, progressed, and then received pembrolizumab plus lenvatinib. Patients were stratified by TFI (<6 months, Cohort 1; ≥6 months, Cohort 2) and matched 1:1 by propensity score. The primary outcome was overall survival (OS), compared using Kaplan–Meier and Cox proportional-hazards methods; adverse-event risks were exploratory outcomes compared using z-tests for the risk difference, without adjustment for multiple comparisons. Results: Of 420 eligible patients, 119 remained in each cohort after matching, with balanced baseline characteristics. Median OS was 10.0 months in Cohort 1 versus 23.6 months in Cohort 2 (hazard ratio 1.60, 95% confidence interval 1.12–2.29; p = 0.009), and 3-year OS was 32.5% versus 40.5%. Grade 3 anemia occurred earlier and more often in Cohort 1 (hazard ratio 1.74, 95% confidence interval 1.10–2.76; p = 0.017), whereas hypothyroidism was less frequent (31.9% versus 47.1%; p = 0.017); the remaining adverse events did not differ significantly between cohorts. Conclusions: A TFI ≥ 6 months is associated with significantly longer OS and a largely similar toxicity profile. The TFI is a readily available, real-world evidence-based reference for the prognosis and for the comparative adverse-event profile of the two TFI groups in this setting.