Programmed death-ligand expression and lymph node involvement in penile squamous cell carcinoma

Purpose: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC. Materials and methods: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive. Results: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188). Conclusions: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.