Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors

Abstract

Background: We developed a novel risk scoring system for urothelial cancer (UC) patients receiving immune checkpoint inhibitors (ICI). Methods: We conducted a retrospective review of 67 UC patients treated with ICI at Winship Cancer Institute of Emory University from 2015 to 2018. Using stepwise variable selection in Cox proportional hazard model and Sullivan's weighting schema, baseline platelet-to-lymphocyte ratio (PLR), presence of liver metastasis, baseline albumin, and baseline Eastern Cooperative Oncology Group performance status (ECOG PS) were used for risk scoring. Patients were categorized into good risk (risk score 0-1), intermediate risk (risk score 2-3), and poor risk (risk score 4-6). Univariable (UVA) and multivariable analysis (MVA) and Kaplan-Meier method were used to assess overall survival (OS) and progression free survival (PFS). Results: The Emory Risk Scoring System had C-statistics of 0.74 (Standard Error = 0.047) in predicting OS and 0.70 (Standard Error = 0.043) in predicting PFS. Compared to good risk patients, poor risk patients had significantly shorter OS and PFS in both UVA and MVA (all P < .001), and intermediate risk patients had significantly shorter OS and PFS in both UVA and MVA (all P < .03). Conclusions: Risk scoring using baseline PLR, presence of liver metastasis, baseline albumin, and baseline ECOG PS may effectively predict OS and PFS in UC patients receiving ICI. K E Y W O R D S cancer risk factors, immunology, risk assessment, urological oncology | 2753 SHABTO eT Al. 2758 | SHABTO eT Al. ACKNOWLEDGMENTSPreliminary data on the effects of inflammatory markers and sites of metastasis on survival outcomes in urothelial cancer patients at our institution was presented at the 2019 GU ASCO Meeting in San Francisco, California. CONFLICT OF INTERESTBCC has a consulting/advisory role with Astellas Medivation, Pfizer, and Blue Earth Diagnostics and receives travel accommodations from Bristol-Myers Squibb. MAB has a consulting/advisory role with Exelixis, Nektar, and

Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort

“…A risk scoring using baseline platelet-to-lymphocyte ratio, presence of liver metastasis, albumin, and ECOG PS has been developed on a cohort of 67 UC patients treated with ICIs. 28 A three-factor model including genomic (namely, a single-nucleotide variant count >9) and clinical (i.e. NLR <5 and lack of visceral metastasis) variables was related to benefit from ICI but not from taxane therapy in 62 patients with metastatic UC.…”

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

“…Sonpavde et al (2016) ultimately improved the concordance statistic of their model incorporating ECOG PS, hemoglobin, liver metastasis, and TFPC from 0.616 to 0.646 by adding low albumin, a known marker of inflammation, as a fifth and final factor in their prognostic classification of patients receiving chemotherapy in the salvage setting [39]. While investigating the factors most predictive of clinical outcomes in patients with metastatic UC treated with ICI, our own group developed the Emory Risk Scoring System that associates increased baseline platelet‐lymphocyte ratio, low baseline albumin, metastasis to the liver, and higher ECOG PS with decreased survival [11]. Associating elevated levels of systemic inflammation through a variety of biomarker proxies with prognosis is a path often traveled, as evidenced above.…”

“…Systemic inflammation alone and in combination with other clinical factors has been shown to predict poorer response to ICI across genitourinary cancers including UC [8][9][10][11][12][13][14]. C-reactive protein (CRP) is an acute phase reactant that increases in response to proinflammatory cytokines such as interleukin (IL)-6 and IL-1β and has negative prognostic value across multiple malignancies and stages [15,16].…”

Inflammatory Markers in Cancer Immunotherapy

“…Interestingly, Shabto et al reported a novel risk stratification system for urothelial carcinoma patients treated with ICI using platelet-to-lymphocyte risk as an inflammatory marker in addition to Eastern Cooperative Oncology performance status (ECOG PS), presence of liver metastasis, and albumin [ 37 ].High PLR was seen to be demonstrating shorter PFS and OS compared to patients with low PLR with NSCLC treated with atezolizumab [ 28 ]. Higher PLR of >168.13 before the fifth dose of ICIs was noted to be a prognostic marker and correlated with smaller OS in patients with NSCLC receiving nivolumab and durvalumab [ 38 ].…”