Prognostic Value of Systemic Inflammatory Biomarkers in Patients with Metastatic Renal Cell Carcinoma

Prognostic and predictive biomarkers for metastatic renal cell carcinoma

“…Overall, we found the strongest consensus for serum levels of CAIX [16] , COP-NLR [17] , CRP [18] , s-TATI [19] , and VEGF [15,16,20] , gene mutations in BAP1 [23] , CDKN2A [24] , CIMP/FH [24] , and TERT [23] , gene expression of ERV [35,36] , and NQO1 [24] , and histologic expression of CAIX [21,37] and macrophage infiltration [38] as prognostic biomarkers for OS and PFS. Tables 1 and 2, Supplementary Tables 1 and 2 list all identified data depicting RR = 2.56, P < 0.0001 ccRCC HR = 1.35, P < 0.001 (CSS HR = 1.32, P < 0.001) PLR (high vs. low) [17,62] P or S HR = 1.57, P = 0.002 276 ‡ s-TATI (high vs. low) [19] HR = 1.01, P = 0.03 (CSS HR = 1.01, P = 0.004) HR = 1.0, 95%CI: 1.0-1.0 TIMP-1 mRNA (high vs. low) [16,22] Associated, P = 0.030 VEGF (continuous) [20] Placebo Shorter, P = 0.0231 Shorter, P = 0.0416 VEGF (high vs. low) [20] Sorafenib P = 0.0145 WBC (high vs. low) [15] RR = 1.37, P < 0.0001 ‡Total sample size of study (n of direct comparison not available).…”

“…Overall, we found the strongest consensus for serum levels of CAIX [16] , COP-NLR [17] , CRP [18] , s-TATI [19] , and VEGF [15,16,20] , gene mutations in BAP1 [23] , CDKN2A [24] , CIMP/FH [24] , and TERT [23] , gene expression of ERV [35,36] , and NQO1 [24] , and histologic expression of CAIX [21,37] and macrophage infiltration [38] as prognostic biomarkers for OS and PFS. Tables 1 and 2, Supplementary Tables 1 and 2 list all identified data depicting RR = 2.56, P < 0.0001 ccRCC HR = 1.35, P < 0.001 (CSS HR = 1.32, P < 0.001) PLR (high vs. low) [17,62] P or S HR = 1.57, P = 0.002 276 ‡ s-TATI (high vs. low) [19] HR = 1.01, P = 0.03 (CSS HR = 1.01, P = 0.004) HR = 1.0, 95%CI: 1.0-1.0 TIMP-1 mRNA (high vs. low) [16,22] Associated, P = 0.030 VEGF (continuous) [20] Placebo Shorter, P = 0.0231 Shorter, P = 0.0416 VEGF (high vs. low) [20] Sorafenib P = 0.0145 WBC (high vs. low) [15] RR = 1.37, P < 0.0001 ‡Total sample size of study (n of direct comparison not available). Grey Cell: positive association; White Cell: negative association; ICI: immune checkpoint inhibitor, INFα: interferon alpha, Ip: ipilimumab; N: nivolumab; P: pazopanib; S: sunitinib; CSS: cancer specific survival; DFS: disease free survival; HR: hazard ratio; OS: overall survival; PFS: progression free survival; RR: relative risk; ALP: alkaline phosphatase; Ca: calcium; COP-NLR: combined platelet count and neutrophil to lymphocyte ratio; CRP: C-reactive protein; Hg: hemoglobin; LDH: lactate dehydrogenase; NLR: neutrophil to lymphocyte ratio; ccRCC: clear cell RCC; PLR: platelet to lymphocyte ratio; s-TATI: serum tumor-associated trypsin inhibitor; TIMP: tissue inhibitor matrix metalloproteinase; VEGF: vascular endothelial growth factor; WBC: white blood cell.…”

“…Serum biomarkers, such as ALP, corrected calcium, Hg, LDH, neutrophil count, and platelets have been extensively validated as prognostic biomarkers for OS and CSS by MSKCC [10] , CCF [11] , IMDC [12] , Groupe Français d'Immunothérapie [14] , International Kidney Cancer Working Group [15] and others [Table 1, Supplementary Table 1]. Additional promising serum biomarkers include elevated carbonic anhydrase IX (CAIX) being potentially prognostic of improved PFS and OS [16] , while elevated COP-NLR [17] , elevated CRP [18] , s-TATI [19] , and VEGF [15,16,20] may be prognostic for decreased PFS and/or OS [19] . Conflicting or inconclusive evidence exists regarding Ras p21 [21] , sVEGF-r [16] , TIMP-1 mRNA [16,22] .…”

“…Additional promising serum biomarkers include elevated carbonic anhydrase IX (CAIX) being potentially prognostic of improved PFS and OS [16] , while elevated COP-NLR [17] , elevated CRP [18] , s-TATI [19] , and VEGF [15,16,20] may be prognostic for decreased PFS and/or OS [19] . Conflicting or inconclusive evidence exists regarding Ras p21 [21] , sVEGF-r [16] , TIMP-1 mRNA [16,22] . For example, elevated TIMP-1 mRNA has been positively associated with metastasis and OS in one study [22] but negatively associated with OS in another [16] .…”

“…Conflicting or inconclusive evidence exists regarding Ras p21 [21] , sVEGF-r [16] , TIMP-1 mRNA [16,22] . For example, elevated TIMP-1 mRNA has been positively associated with metastasis and OS in one study [22] but negatively associated with OS in another [16] . Among certain patient populations, mutated alleles that may be prognostic for poorer OS or PFS compared to wild type (WT) include loss of function (LOF) mutations or alterations in BAP1 [23] , CDKN2A [24] , CIMP /FH [24] , and TERT [23] [Table 2, Supplementary Table 2].…”