title: Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.
  
  
  OBJECTIVE
  To investigate the prognostic role of PD-L1 expression in patients affected by renal cell carcinoma (RCC).
  
  
  METHODS
  MEDLINE/PubMed, the Cochrane Library, and ASCO University were searched for studies investigating the prognostic role of PD-L1 expression in RCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
  
  
  RESULTS
  Six studies and 1323 cases were included in the final analysis. PD-L1 was expressed in 24.2 % of clear cell tumors compared to 10.9 % of non-clear cell tumors (p = 0.002). In the overall population, a higher level of PD-L1 expression increased the risk of death by 81 % (HR; 1.81, 95 % CI 1.31-2.49; p < 0.001). When the analysis was restricted to cases evaluated by immunohistochemistry alone, the higher expression of PD-L1 more than doubled the risk of death (HR; 2.05, 95 % CI 1.38-3.05; p < 0.001). In clear cell histology, higher PD-L1 expression increased the risk of death by 53 % (HR; 1.53, 95 % CI 1.27-1.84; p < 0.001), while in metastatic patients, the evaluation of PD-L1 expression on primary tumors revealed that it retains its prognostic role (HR; 1.45, 95 % CI 1.08-1.93; p = 0.01).
  
  
  CONCLUSIONS
  Significant heterogeneity has been identified among the included studies. As a consequence, cautious interpretation of the results is recommended.
  
  
  CONCLUSIONS
  This meta-analysis indicates that a higher level of PD-L1 expression is a negative prognostic factor in RCC. Its validation as an independent prognostic factor compared to other traditionally used clinical parameters in localized or advanced disease is recommended.
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy. roberto.iacovelli@alice.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verri
authors.affiliation: Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Renne
authors.affiliation: Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Piazzale C. Golgi 19, 27100, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Paglino
authors.affiliation: Medical Oncology, Polytechnic University of the Marche Region, AOU Ospedali Riuniti, via Conca 71, 60126, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cossu Rocca
authors.affiliation: Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Piazzale C. Golgi 19, 27100, Pavia, Italy.
authors.forename: Palma
authors.initials: P
authors.lastname: Giglione
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.affiliation: Medical Oncology Division of Urogenital and Head & Neck Tumours, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cullurà
authors.affiliation: Medical Oncology, Polytechnic University of the Marche Region, AOU Ospedali Riuniti, via Conca 71, 60126, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Piazzale C. Golgi 19, 27100, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human