The prognostic role of PD-L1 in penile squamous cell carcinoma: A systematic review and meta-analysis.

Abstract

13 Background: Penile squamous cell carcinoma (PSCC) is a rare tumor with limited therapeutic options in advanced disease. Given the role of PD-L1 as a prognostic biomarker in many cancer subtypes, assessing its value in PSCC may inform prognosis and guide the use of immune checkpoint inhibitors in metastatic disease. In this systematic review and meta-analysis, we evaluate the prevalence of PD-L1 tumor expression in PSCC and assess its prognostic association with overall survival (OS), cancer-specific survival (CSS), and lymph node metastasis (LNM). Methods: We searched PubMed, Embase and Cochrane for relevant studies. The primary outcomes were OS, CSS, and LNM, analyzed using HRs or ORs, each with 95% CIs. Outcomes were prespecified in the PROSPERO protocol (CRD42019129410). Random-effects meta-analyses (restricted maximum-likelihood estimator) were performed using inverse-variance weighting. Heterogeneity was assessed by Q, τ², and I² statistics. Publication bias was examined by Egger’s test and funnel plots. Results: Fifteen retrospective studies were included (N = 1,445). Overall, 57% of tumors were PD-L1 positive (IQR, 44%–66%). Among 796 patients, PD-L1 expression was significantly higher in HPV-negative than in HPV-positive tumors (42% vs 13.5%). Eight studies (N = 930) evaluated OS, nine studies (N = 1,091) assessed CSS, and five studies (N = 622) investigated LNM. PD-L1 positivity was associated with reduced OS (HR 1.52; 1.12–2.05; I² = 6.8%) and CSS (HR 1.61; 1.16–2.23; I² = 38.3%), and with higher odds of LNM (OR 2.94; 1.28–6.78; I² = 57.3%). In meta-regression, HPV adjustment significantly strengthened CSS associations (QM = 7.13, p = 0.008; HR = 2.06, 1.21–3.51), accounting for all observed heterogeneity. Other moderators (sample size, adjustment status, tumor stage, study location, tumor-cell vs TIL scoring) were non-significant. Conclusions: PD-L1 expression is more frequent in HPV-negative PSCC and is consistently associated with adverse clinical outcomes, including shorter OS, shorter CSS, and higher odds of LNM. These findings support PD-L1 as a potential prognostic biomarker in PSCC and underscore the importance of considering HPV status in prognostic and therapeutic stratification.