Lower neutrophil‐to‐lymphocyte ratio and positive programmed cell death ligand‐1 expression are favorable prognostic markers in patients treated with pembrolizumab for urothelial carcinoma

Abstract

Background: Immune checkpoint inhibitors (ICIs) are effective in some cancer patients; however, they may show no efficacy in others. Predictive biomarkers are crucial for appropriately selecting the patients who receive ICI therapy. This study aimed to clarify the predictors of disease progression in urothelial carcinoma (UC) patients treated with an ICI, pembrolizumab. Methods: We analyzed the response patterns of 50 UC patients who were treated with pembrolizumab, as well as the association between survival and clinicopathological factors. Clinical factors included age, sex, body mass index, clinical courses, laboratory data, metastases, and adverse events. Pathological factors included special variant, squamous differentiation, programmed cell death ligand-1 (PD-L1) expression, CD8-positive lymphocytes density, and CDKN2A/p16 homozygous deletion.Results: During pembrolizumab treatment, four (8%), 11 (22%), and eight (16%) patients achieved the best-case scenarios of complete response, partial response, and stable disease, respectively. Twenty-seven patients (54%) showed progressive disease. In this study, younger age, lower preoperative neutrophil-to-lymphocyte ratio (NLR), and positive PD-L1 expression were significantly correlated with longer progression-free survival and overall survival. Moreover, lower NLR and positive PD-L1 expression were independently associated with longer OS in multivariate analysis.Conclusions: Based on our observations, lower NLR and positive PD-L1 expression may be independent favorable prognostic markers in UC patients treated with pembrolizumab. These results suggest that both host and tumor status can reflect the effectiveness of pembrolizumab among patients with UC.

Prognostic role of circulating cytokines and inflammation indexes for avelumab maintenance in metastatic urothelial carcinoma

“…In mUC, most studies included small cohorts treated with second-line pembrolizumab. Fifty patients with mUC treated by Miyama and colleagues achieved longer PFS and OS, although the results only narrowed the statistical significance (p=0.0056 for PFS, p=0.0054 for OS) (14). In 29 patients treated by Shimizu and colleagues, NLR predicted PFS (16).…”

“…Besides cytokines production and interaction, immune cells are also involved in inflammation, one of the hallmarks of cancer. Therefore, some inflammatory indexes, such as the neutrophil-lo-lymphocyte ratio (NLR), could reflect the antitumor immune response and inflammatory status, and have been correlated with response and survival after ICIs already in other tumor subtypes (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Prognostic Utility of the Modified Glasgow Prognostic Score in Urothelial Carcinoma: Outcomes from a Pooled Analysis

“…Cancer-related inflammation is the seventh hallmark of cancer, and inflammatory cytokines produced by tumors and related host cells affect tumor characteristics, including survival, proliferation, angiogenesis, and the metastasis of malignant cells [ 43 ]. Therefore, in addition to individual patient and tumor characteristics, clinical markers such as the neutrophil-to-lymphocyte ratio, insulin-like growth factor-I and its binding protein, insulin-like growth factor-I binding protein-2 and -3, the platelet-lymphocyte ratio [ 44 , 45 , 46 ], molecular markers such as molecular subtypes, circulating tumor cells, and DNA damage repair-gene defects are also used to predict the prognosis of UC [ 47 , 48 , 49 ].…”

Real‐world outcomes of pembrolizumab for platinum‐refractory advanced urothelial carcinoma: Efficacy, safety, and evidence for trial‐unfit patients

“…Several inflammatory and nutritional factors were reported to be prognostic for UC patients who received pembrolizumab. The most studied factors include neutrophil‐lymphocyte ratio (NLR), C reactive protein (CRP), hemoglobin, albumin, and its combination 15,16,22,26–38 . A recent meta‐analysis summarized that higher NLR (pooled hazard ratio [HR] 1.29) and CRP (pooled HR 2.49) are significantly associated with the OS 39 .…”