title: The current status of checkpoint inhibitors in metastatic bladder cancer.
abstract: For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.
authors.affiliation: Department of Urology, Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia.|Department of Urology, University Hospital Tuebingen, Eberhard-Karls University, Hoppe-Seyler Street 3, 72076, Tuebingen, Germany.
authors.forename: Omar
authors.initials: O
authors.lastname: Fahmy
authors.affiliation: Department of Urology, Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia.
authors.forename: Mohd Ghani
authors.initials: MG
authors.lastname: Khairul-Asri
authors.affiliation: Department of Urology, University Hospital Tuebingen, Eberhard-Karls University, Hoppe-Seyler Street 3, 72076, Tuebingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, University Hospital Tuebingen, Eberhard-Karls University, Hoppe-Seyler Street 3, 72076, Tuebingen, Germany. georgios.gakis@med.uni-tuebingen.de.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D018816:Genes, cdc / Q000187:drug effects; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077594:Nivolumab; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D000077594:Nivolumab; C582435:pembrolizumab
keywords: Bladder cancer immunotherapy; Checkpoint inhibitor; Ipilimumab; Nivolumab; Pembrolizumab