The impact of programmed death ligand 1 expression on prognosis in penile cancer: a systematic review and meta‐analysis

OBJECTIVES: To determine the prevalence of programmed death ligand 1 (PD-L1) expression in penile squamous cell carcinoma (PSCC) and evaluate its associations with clinicopathological features and survival outcomes. PATIENTS AND METHODS: A systematic review was carried out using PubMed, the Excerpta Medica dataBASE (EMBASE), Scopus, Web of Science and Cochrane. Random-effects meta-analysis synthesised prevalence, hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS), and odds ratios (ORs) for lymph node metastases (LNM) and tumour characteristics. Meta-regression was caried out for pre-specified moderators. RESULTS: A total of 16 studies (1634 patients) were included, with median follow-up of 44 months. The pooled PD-L1 prevalence was 53% (95% confidence interval [CI] 44-62%) with substantial between-study heterogeneity. PD-L1 positivity was associated with worse CSS (HR 1.94, 95% CI 1.54-2.44; P < 0.001) but not OS (HR 1.28, 95% CI 0.89-1.86; P = 0.2). PD-L1 positivity was associated with higher tumour stage (pathological T stage [pT]1 vs pT2-4, OR 1.67, 95% CI 1.22-2.29, P = 0.001), higher tumour grade (Grade 1 vs Grade 2-3, OR 2.60, 95% CI 1.94-3.5, P < 0.001), and LNM (OR 2.32, 95% CI 1.57-3.42, P < 0.001). Sensitivity testing and meta-regression did not materially alter pooled effects. CONCLUSIONS: Programmed death ligand 1 is associated with adverse clinicopathological features and worse CSS in PSCC. Prospective validation is required to assess its independent prognostic value. Similarly PD-L1's predictive value for immunotherapy benefit cannot be determined from the current evidence and requires evaluation with treatment-specific prospective studies.