Impact of Postoperative C-Reactive Protein Level on Recurrence and Prognosis in Patients With N0M0 Clear Cell Renal Cell Carcinoma

Ito, Keiichi; Yoshii, Hidehiko; Sato, Akinori; Kuroda, Kenji; Asakuma, Junichi; Horiguchi, Akio; Sumitomo, Makoto; Asano, Tomohiko

doi:10.1016/j.juro.2011.03.113

Cited by 20 publications

(21 citation statements)

References 23 publications

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“…This is consistent with recent publications in cancer cohorts using the same threshold measurement. [15][16][17] The results of the current study are also in agreement with those of previous reports 18 that indicated, in patients with non-small cell lung cancer, although an increased risk of mortality occurs with a C-reactive protein measurement above approximately 4 mg/L, the risk increase is steeper between 8 mg/L and 16 mg/L. Indeed, some authors have adopted other thresholds for C-reactive protein, such as > 5 mg/L, into the GPS.…”

Section: Optimization Of the Gps/proctor Et Almentioning

confidence: 99%

Optimization of the systemic inflammation‐based Glasgow Prognostic Score

Proctor

Horgan

Talwar

et al. 2013

Cancer

105

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BACKGROUND The modified Glasgow Prognostic Score (mGPS), an inflammation‐based prognostic score that uses thresholds of C‐reactive protein (> 10 mg/L) and albumin (< 35 g/L), has been found to be independently prognostic of survival in patients with cancer. The objective of the current study was to establish whether the addition of a differential leukocyte count and a high‐sensitivity C‐reactive protein measurement enhanced the prognostic value of the mGPS. METHODS A total of 12,119 patients who had an incidental blood sample taken between 2000 and 2007 for C‐reactive protein, albumin, and a differential leukocyte count as well as a diagnosis of cancer made within 2 years were identified. This group was studied for the prognostic value of neutrophil, lymphocyte, and platelet counts. In addition 2742 patients whose blood was sampled after the introduction of high‐sensitivity C‐reactive protein measurements were studied for the prognostic value of different thresholds. RESULTS Using cancer‐specific survival as an endpoint, the prognostic value of the mGPS (hazard ratio [HR], 2.61; P < .001 [area under the receiver operating characteristic curve (AUC), 0.695]) was found to be improved by the addition of neutrophil and platelet counts (HR, 4.86; P < .001 [AUC, 0.734]) and a high‐sensitivity C‐reactive protein measurement (> 3 mg/L) (HR, 5.77; P < .001 [AUC, 0.734]). CONCLUSIONS The results of the current study demonstrate that the addition of neutrophil and platelet counts, as well as a high‐sensitivity C‐reactive protein measurement, enhanced the prognostic value of the mGPS. Cancer 2013;119:2325–2332. © 2013 American Cancer Society.

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Section: Optimization Of the Gps/proctor Et Almentioning

confidence: 99%

Optimization of the systemic inflammation‐based Glasgow Prognostic Score

Proctor

Horgan

Talwar

et al. 2013

Cancer

105

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“…A decrease in CRP level (to <0.5 mg/dl) during treatment predicts better prognosis in patients with metastatic RCC, and a prolonged period of normal CRP level is associated with prolonged survival (15). Ito et al (16) reported that non-normalization of postoperative CRP (≥0.3 mg/dl) strongly predicted recurrence and prognosis in 263 patients with N0M0 RCC who underwent nephrectomy. Shinohara et al (17) reported that response rate and 1-year progression-free survival were significantly higher in patients with normalized CRP compared with those in non-normalized patients treated with IFN-α combination therapy.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Tatokoro et al (14) reported that CRP decreased to normal after cytoreductive nephrectomy in 74% of patients who had elevated CRP prior to surgery, and Ito et al (16) reported that 65.8% of patients achieved CRP normalization following nephrectomy. By contrast, Saito et al (15) reported that, among patients who underwent immunotherapy, metastasectomy, or both, only 49% achieved CRP normalization.…”

Section: Discussionmentioning

confidence: 99%

“…However, the prognostic role of CRP kinetics after sunitinib initiation has not been investigated to date. Previous studies have demonstrated that postoperative normalization of the CRP level is associated with better prognosis in patients with localized or advanced RCC who receive nephrectomy, metastasectomy, or both (13)(14)(15)(16). In addition, CRP kinetics has been found to be a prognostic factor for the effect of cytokine therapies (13,15,17).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic effect of serum C-reactive protein kinetics on advanced renal cell carcinoma treated with sunitinib

Fujita

Tabata

Ishii

et al. 2017

Molecular and Clinical Oncology

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Abstract. C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the prognostic effect of pretreatment serum CRP level and CRP kinetics on patients with advanced RCC treated with sunitinib. A total of 56 consecutive patients with advanced RCC treated with sunitinib between December, 2008 and December, 2012 were enrolled in the present study. The patients were retrospectively divided into 3 cohorts according to pretreatment serum CRP level and CRP kinetics: i) Normal CRP cohort (pretreatment CRP ≤0.30 mg/dl); ii) normalized CRP cohort (pretreatment CRP >0.30 mg/dl that normalized within 2 cycles of treatment); and iii) non-normalized CRP cohort (pretreatment CRP >0.30 mg/dl that did not normalize after sunitinib initiation). Disease control rate, progression-free survival and overall survival times were compared for the 3 cohorts. The normal (n=17, 30.4%) and the normalized (n=8, 14.3%) CRP cohorts exhibited significantly better disease control rates compared with the non-normalized CRP cohort (n=31, 55.4%; P<0.0001 and P=0.0445, respectively). The normal CRP cohort exhibited significantly longer progression-free survival compared with the non-normalized CRP cohort (P=0.0050). The normal and normalized CRP cohorts exhibited significantly longer overall survival compared with the non-normalized CRP cohort (P=0.0005 and 0.0466, respectively). Therefore, CRP kinetics and normal pretreatment CRP level are prognostic indicators in patients with advanced RCC treated with sunitinib. IntroductionC-reactive protein (CRP), which was found to be a representative acute-phase reactant in 1930, is the most widely used marker of systemic inflammation (1). Inflammation plays an important role during almost all stages of tumor development (2). For example, the proliferation of renal cell carcinoma (RCC) is associated with increased levels of interleukin-6 (IL-6), nuclear factor-κB, and other inflammatory factors (3,4), and the serum CRP levels were found to be correlated with the levels of proinflammatory cytokines, such as IL-6 (5). Numerous studies have demonstrated that CRP is a significant prognostic factor among patients with RCC at various stages, whether they are being treated by surgery, systemic therapy, or both (6).Sunitinib malate (Sutent, Pfizer Inc., New York, NY, USA) is an orally administered, small-molecule, multitargeted inhibitor of tyrosine kinases (e.g., vascular endothelial growth factor receptor, platelet-derived growth factor receptor, phosphorylation of stem cell factor receptor, Fms-like tyrosine kinase-3, colony-stimulating factor-1 receptor, and RET receptor tyrosine kinases). In a phase III clinical trial including patients with advanced RCC, sunitinib achieved significantly better results compared with interferon (IFN)-α and is approved worldwide for the treatment of advanced RCC (7,8). The number of patients treated with sunitinib is increasing and, therefore, there is an urgent need to identify biomarkers that may...

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“…Other potential tissue biomarkers that were tested failed to predict RCC recurrence in our cohort. Although, serum CRP levels have been shown to be predictive for RCC outcomes in several studies [29,30], few studies have evaluated tissue expression of CRP [11]. In addition, HIF1α, HIF2α, and CAIX have shown variable ability to predict recurrence or survival in several studies [3,10,21,27].…”

Section: Discussionmentioning

confidence: 99%

Analysis and validation of tissue biomarkers for renal cell carcinoma using automated high-throughput evaluation of protein expression

et al. 2014

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Summary The objective of this study was to compare the predictive ability of potential tissue biomarkers to known prognostic factors that predict renal cell carcinoma (RCC) recurrence using an automated system of immunohistochemical analysis. After institutional review board approval, a tissue microarray was constructed using tissue from patients who had partial or radical nephrectomy for RCC. Patients with metastatic disease were excluded. Immunohistochemical staining of the tissue microarray for Ki-67, C-reactive protein, carbonic anhydrase 9, and hypoxia-inducible factors 1α and 2α was analyzed using automated image analysis. Univariable and multivariable analyses were performed to evaluate the association of putative biomarkers and known prognostic factors. Of 216 patients who met the entrance criteria, 34 (16%) patients developed metastatic recurrence within a median follow-up interval of 60.9 (interquartile range, 13.9–87.1) months. RCC morphotypes analyzed in this study include clear cell (n = 156), papillary (n = 38), chromophobe (n = 16), and collecting duct/unclassified (n = 6). Univariate analysis identified that only increased Ki-67 was predictive of RCC recurrence among the proteins evaluated, in addition to other known clinicopathological prognostic factors. After multivariate analysis, Ki-67 was identified as an independently predictive risk factor for RCC recurrence (hazard ratio [HR], 3.73 [confidence interval {CI}, 1.60–8.68]). Other independent predictors of RCC recurrence included tumor diameter (HR, 1.20 [CI, 1.02–1.41]) and perinephric fat invasion (HR, 4.49 [CI, 1.11–18.20]). We conclude that Ki-67 positivity is independently predictive of RCC recurrence after surgery in nonmetastatic patients. Automated analysis of tissue protein expression can facilitate a more objective and expedient investigation of tissue biomarkers for RCC.

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Impact of Postoperative C-Reactive Protein Level on Recurrence and Prognosis in Patients With N0M0 Clear Cell Renal Cell Carcinoma

Abstract: Nonnormalization of postoperative C-reactive protein is a strong predictor of recurrence and prognosis. Patients with C-reactive protein 0.3 mg/dl or greater at recurrence might not survive as long as those with C-reactive protein less than 0.3 mg/dl at recurrence.

Cited by 20 publications

References 23 publications

Optimization of the systemic inflammation‐based Glasgow Prognostic Score

Optimization of the systemic inflammation‐based Glasgow Prognostic Score

Prognostic effect of serum C-reactive protein kinetics on advanced renal cell carcinoma treated with sunitinib

Analysis and validation of tissue biomarkers for renal cell carcinoma using automated high-throughput evaluation of protein expression

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