Baseline Modified Glasgow Prognostic Score Associated with Survival in Metastatic Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors

Abstract

Background The modified Glasgow prognostic score (mGPS), a clinical tool that incorporates albumin and C‐reactive protein, has proven useful in the prognostication of multiple cancers. Several immune checkpoint inhibitors (ICIs) have been approved for the treatment of metastatic urothelial cell carcinoma (mUC), but a prognostic biomarker is needed. We investigated the impact of mGPS on survival outcomes in patients with mUC receiving ICIs. Materials and Methods We retrospectively reviewed patients with mUC treated with ICIs (programmed cell death protein 1 or programmed cell death ligand 1 inhibitors) at Winship Cancer Institute from 2015 to 2018. Overall survival (OS) and progression‐free survival (PFS) were measured from the start date of ICI until death or clinical or radiographic progression, respectively. mGPS was defined as a summary score with one point given for C‐reactive protein >10 mg/L and/or albumin <3.5 g/dL. Univariate (UVA) and multivariate (MVA) analyses were carried out using Cox proportional hazard model. These outcomes were also assessed by Kaplan‐Meier analysis. Results A total of 53 patients were included with a median follow‐up 27.1 months. The median age was 70 years, with 84.9% male and 20.8% Black. Baseline mGPS was 0 in 43.4%, 1 in 28.3% and 2 in 28.3%. Increased mGPS at the time of ICI initiation was associated with poorer OS and PFS in UVA, MVA, and Kaplan‐Meier analyses. Conclusion The mGPS may be a useful prognostic tool in patients with mUC when treatment with ICI is under consideration. These results warrant a larger study for validation. Implications for Practice The ideal prognostic tool for use in a busy clinical practice is easy‐to‐use, cost‐effective, and capable of accurately predicting clinical outcomes. There is currently no universally accepted risk score in metastatic urothelial cell carcinoma (mUC), particularly in the immunotherapy era. The modified Glasgow prognostic score (mGPS) incorporates albumin and C‐reactive protein and may reflect underlying chronic inflammation, a known risk factor for resistance to immune checkpoint inhibitors (ICIs). This study found that baseline mGPS is associated with survival outcomes in patients with mUC treated with ICIs and may help clinicians to prognosticate for their patients beginning immunotherapy.

The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

“…Overall, CRP is an independent and desirable predictive biomarker of OS and PFS in cancer patients receiving ICI treatment, and quantifying CRP through blood examination is convenient and less invasive. The combination of CRP and other predictors to form a predictive model is also a feasible idea that merits investigation ( 53 , 63 , 64 ). In addition, for cancer patients with high CRP levels, the handling of inflammation and TME should be of particular attention to reduce resistance to ICIs ( 17 ).…”

Peripheral Blood Biomarkers Predictive of Efficacy Outcome and Immune-Related Adverse Events in Advanced Gastrointestinal Cancers Treated with Checkpoint Inhibitors

“…Dysregulation of the balance might be involved in the pathogenesis of irAEs. ECOG PS and baseline albumin reflect the physical status and nutrition reserves of patients, respectively, which have been widely recognized as prerequisites for antitumor responses [ 40 ]. LDH represents the metabolic activity of the body glucometabolic, which is proportional to tumor burden and is correlated with poor response to immunotherapy [ 66 ].…”

“…These indicators are both economical and accessible. In addition, albumin and lactate dehydrogenase (LDH) are parameters derived from routine blood biochemistry, which are linked with metabolic homeostasis and affect the therapeutic outcomes of immunotherapy [ 33 , 34 , 39 , 40 ]. Interestingly, the development of irAEs is strongly correlated with favorable prognosis in patients treated with ICIs.…”

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

“…As far as ICIs are concerned, inflammatory indices have been mostly studied in patients with advanced NSCLC and melanoma [ 89 , 90 ], while fewer and smaller studies have been conducted in patients treated with ICIs for genitourinary tumours, including UC [ 62 , 63 , 65 , 69 , 70 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. The inflammatory indices most commonly studied in patients with UC treated with ICIs include the neutrophil-to-lymphocyte ratio (NLR), baseline platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and albumin.…”

“…The inflammatory indices most commonly studied in patients with UC treated with ICIs include the neutrophil-to-lymphocyte ratio (NLR), baseline platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and albumin. High levels of NLR, PLR, LDH and CRP, and low levels of albumin have been correlated with worse survival and efficacy outcomes, either as single parameters or within combined prognostic scores [ 62 , 63 , 65 , 69 , 70 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ].…”