Pretreatment clinical and hematologic prognostic factors of metastatic urothelial carcinoma treated with pembrolizumab: a systematic review and meta-analysis

Abstract

Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients’ demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57–4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42–2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18–8.20), higher neutrophil–lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07–1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52–4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.

Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review

“…All previous meta-analyses about immunotherapy and NLR focused on the impact of baseline NLR on prognosis [ 60 , 61 , 62 , 63 , 64 , 65 ]. Although a small part of the meta-analyses included a few studies addressing the dynamics of NLR, they did not conduct quantitative analysis and did not arrive at a specific conclusion [ 60 , 61 ].…”

Prognostic nutritional index of early post‑pembrolizumab therapy predicts long‑term survival in patients with advanced urothelial carcinoma

“…Along with the search for histological biomarkers, hematological biomarkers have also been explored (5). Pretreatment baseline hematological parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been studied (16)(17)(18)(19).…”

“…Unfortunately, only a minority of patients benefits from pembrolizumab. Establishing biomarkers to predict the efficacy of this drug is therefore an important challenge ( 5 ).…”

Low Skeletal Muscle Mass Predicts Relevant Outcomes in Palliative Urological Oncology: A Systematic Review and Meta-Analysis

“…Already established prognostic factors in RCC are pathologic stage, lymph node status, and histologic grade [34]. For metastasized UC, the presence of liver metastasis, poor performance status, high C-reactive protein, and high neutrophil-lymphocyte ratio were independent prognostic factors under immunotherapy [35]. It would be interesting to study whether LSMM could be added as another independent prognostic factor.…”

“…The importance of muscle mass quantification based on imaging has a great clinical relevance. As such, one important point for the diagnosis of malnutrition is the LSMM assessment with the proposed threshold values [35, 36]. In clinical routine, early diagnosis of malnutrition could provide better nutritional support for advanced cancer patients as part of multimodal therapeutic approaches to maintain or build skeletal muscle mass [35, 36].…”