The impact of programmed death ligand 1 expression on prognosis in penile cancer: a systematic review and meta‐analysis
Diarmuid D. Sugrue, Orla Cullivan, Eoghan Cunnane, Niall Davis, Min Yuen Teo, Ivor CullenObjectives
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.