Programmed Death-Ligand 1, C-reactive Protein, and Neutrophil/Lymphocyte Ratio as Lymphangiogenesis Markers of Metastasis in Penile Cancer – A Systematic Review

Abstract Introduction The spread of penile cancer cells through lymphatic vessels provides the potential for using compounds involved in lymphangiogenesis, such as programmed death-ligand 1 (PD-L1), C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and Ki-67, in predicting the development of lymphatic metastases in penile cancer. Methods The systematic review was conducted based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. A literature search was conducted using the medical literature database PubMed, Scopus, ScienceDirect, EMBASE, and EBSCOHost for studies published until February 7, 2023. Results Among 527 studies identified in the literature, 21 studies met the inclusion criteria and became eligible studies. PD-L1, CRP, and NLR are biomarkers which are proven to be significantly associated with an increased risk of high-grade tumor and lymphatic metastasis in penile cancer. Conclusion PD-L1, CRP, and NLR are biomarkers that might be used to assess the risk or likelihood of developing lymphatic metastases in penile cancer.