Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C‐reactive protein does not improve predictive accuracy

What's known on the subject? and What does the study add? White blood cell count and C‐reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut‐offs for risk stratifications are missing. Therefore, both parameters were re‐evaluated and multivariable analyses revealed a...

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Veröffentlicht in:BJU international 2012-12, Vol.110 (11b), p.E771-E777
Hauptverfasser: Bedke, Jens, Chun, Felix K.‐H., Merseburger, Axel, Scharpf, Marcus, Kasprzyk, Kathrin, Schilling, David, Sievert, Karl‐Dietrich, Stenzl, Arnulf, Kruck, Stephan
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container_end_page E777
container_issue 11b
container_start_page E771
container_title BJU international
container_volume 110
creator Bedke, Jens
Chun, Felix K.‐H.
Merseburger, Axel
Scharpf, Marcus
Kasprzyk, Kathrin
Schilling, David
Sievert, Karl‐Dietrich
Stenzl, Arnulf
Kruck, Stephan
description What's known on the subject? and What does the study add? White blood cell count and C‐reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut‐offs for risk stratifications are missing. Therefore, both parameters were re‐evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer‐specific mortality. However, this CRP‐based prediction added no additional information compared to a clinico‐pathological based model. Objective To re‐evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C‐reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP. Patients and Methods From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer‐specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c‐index). Results In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/μL (hazard ratio [HR] 1.83) and 11.0/μL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P < 0.001) and 0.5 mg/dL (HR 7.15, P < 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer‐specific survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median follow‐up was 57.5 months with 72 (22%) tumour‐related deaths. The final model built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c‐index 0.877) compared with the clinicopathological base model (c‐index 0.881) which included TNM stage, grading and Karnofsky index. Conclusions Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was best to stratify patients at risk of cancer‐specific mortality, but CRP 0.25 mg/dL added no additional information in the prediction model. Therefore we cannot r
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White blood cell count and C‐reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut‐offs for risk stratifications are missing. Therefore, both parameters were re‐evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer‐specific mortality. However, this CRP‐based prediction added no additional information compared to a clinico‐pathological based model. Objective To re‐evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C‐reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP. Patients and Methods From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer‐specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c‐index). Results In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/μL (hazard ratio [HR] 1.83) and 11.0/μL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P &lt; 0.001) and 0.5 mg/dL (HR 7.15, P &lt; 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer‐specific survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median follow‐up was 57.5 months with 72 (22%) tumour‐related deaths. The final model built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c‐index 0.877) compared with the clinicopathological base model (c‐index 0.881) which included TNM stage, grading and Karnofsky index. Conclusions Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was best to stratify patients at risk of cancer‐specific mortality, but CRP 0.25 mg/dL added no additional information in the prediction model. Therefore we cannot recommend measuring CRP as the traditional parameters of TNM stage, grading and Karnofsky index are already of high predictive accuracy.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/j.1464-410X.2012.11642.x</identifier><identifier>PMID: 23134582</identifier><identifier>CODEN: BJINFO</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Accuracy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; biomarkers ; C-Reactive Protein - metabolism ; Cancer ; Carcinoma, Renal Cell - blood ; Carcinoma, Renal Cell - mortality ; Carcinoma, Renal Cell - surgery ; CRP ; Female ; Germany - epidemiology ; Humans ; Inflammation - blood ; Kidney Neoplasms - blood ; Kidney Neoplasms - mortality ; Kidney Neoplasms - surgery ; Male ; Middle Aged ; Neoplasm Staging - methods ; predictive accuracy ; Predictive Value of Tests ; Preoperative Period ; Prognosis ; renal cell cancer ; Reproducibility of Results ; Retrospective Studies ; Studies ; Survival Rate - trends ; systemic inflammation ; threshold ; WBC ; Young Adult</subject><ispartof>BJU international, 2012-12, Vol.110 (11b), p.E771-E777</ispartof><rights>2012 BJU INTERNATIONAL</rights><rights>2012 BJU INTERNATIONAL.</rights><rights>BJUICopyright 2012 BJU International</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5032-477ebcd7a386da56a4543a4cba72f718ac72fdfe9ad9f70e660ba26a96cfbca63</citedby><cites>FETCH-LOGICAL-c5032-477ebcd7a386da56a4543a4cba72f718ac72fdfe9ad9f70e660ba26a96cfbca63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1464-410X.2012.11642.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1464-410X.2012.11642.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23134582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bedke, Jens</creatorcontrib><creatorcontrib>Chun, Felix K.‐H.</creatorcontrib><creatorcontrib>Merseburger, Axel</creatorcontrib><creatorcontrib>Scharpf, Marcus</creatorcontrib><creatorcontrib>Kasprzyk, Kathrin</creatorcontrib><creatorcontrib>Schilling, David</creatorcontrib><creatorcontrib>Sievert, Karl‐Dietrich</creatorcontrib><creatorcontrib>Stenzl, Arnulf</creatorcontrib><creatorcontrib>Kruck, Stephan</creatorcontrib><title>Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C‐reactive protein does not improve predictive accuracy</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>What's known on the subject? and What does the study add? White blood cell count and C‐reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut‐offs for risk stratifications are missing. Therefore, both parameters were re‐evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer‐specific mortality. However, this CRP‐based prediction added no additional information compared to a clinico‐pathological based model. Objective To re‐evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C‐reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP. Patients and Methods From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer‐specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c‐index). Results In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/μL (hazard ratio [HR] 1.83) and 11.0/μL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P &lt; 0.001) and 0.5 mg/dL (HR 7.15, P &lt; 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer‐specific survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median follow‐up was 57.5 months with 72 (22%) tumour‐related deaths. The final model built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c‐index 0.877) compared with the clinicopathological base model (c‐index 0.881) which included TNM stage, grading and Karnofsky index. Conclusions Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was best to stratify patients at risk of cancer‐specific mortality, but CRP 0.25 mg/dL added no additional information in the prediction model. Therefore we cannot recommend measuring CRP as the traditional parameters of TNM stage, grading and Karnofsky index are already of high predictive accuracy.</description><subject>Accuracy</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>biomarkers</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cancer</subject><subject>Carcinoma, Renal Cell - blood</subject><subject>Carcinoma, Renal Cell - mortality</subject><subject>Carcinoma, Renal Cell - surgery</subject><subject>CRP</subject><subject>Female</subject><subject>Germany - epidemiology</subject><subject>Humans</subject><subject>Inflammation - blood</subject><subject>Kidney Neoplasms - blood</subject><subject>Kidney Neoplasms - mortality</subject><subject>Kidney Neoplasms - surgery</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging - methods</subject><subject>predictive accuracy</subject><subject>Predictive Value of Tests</subject><subject>Preoperative Period</subject><subject>Prognosis</subject><subject>renal cell cancer</subject><subject>Reproducibility of Results</subject><subject>Retrospective Studies</subject><subject>Studies</subject><subject>Survival Rate - trends</subject><subject>systemic inflammation</subject><subject>threshold</subject><subject>WBC</subject><subject>Young Adult</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9O3DAQxq2qVaHQV6gscellt_4XJ7kglRWlVEi9FImbNXEmlbdJvLUTYG-8QCWkviFPUmcDHDjVlxmPf_PZno8QytmSp_VpveRKq4Xi7GopGBepqpVY3r4i-88Hr59yVuo98i7GNWOpoLO3ZE9ILlVWiH3y57xvWug6GHzY0k3wP3sfB2dpB-EXhkhdT22LEKjFtqUBe2jn1EKwrvcd0Ie7v6kT_QYDDO4a6erh7j4g2N0maQ6YVGqPkfZ-oK5Lpd0B1m5mwNoxgN0ekjcNtBHfP8YDcvnl9Mfq6-Li-9n56vPFwmZMioXKc6xsnYMsdA2ZBpUpCcpWkIsm5wXYFOsGS6jLJmeoNatAaCi1bSoLWh6Qj7NuesnvEeNgOhenX0GPfoyGS55pKXWWJ_ToBbr2Y0hTSJQoijTTIisTVcyUDT7GgI3ZBJdGuDWcmckyszaTG2ZyxkyWmZ1l5ja1fni8YKw6rJ8bnzxKwPEM3LgWt_8tbE6-Xe5S-Q_kW6ql</recordid><startdate>201212</startdate><enddate>201212</enddate><creator>Bedke, Jens</creator><creator>Chun, Felix K.‐H.</creator><creator>Merseburger, Axel</creator><creator>Scharpf, Marcus</creator><creator>Kasprzyk, Kathrin</creator><creator>Schilling, David</creator><creator>Sievert, Karl‐Dietrich</creator><creator>Stenzl, Arnulf</creator><creator>Kruck, Stephan</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>201212</creationdate><title>Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C‐reactive protein does not improve predictive accuracy</title><author>Bedke, Jens ; Chun, Felix K.‐H. ; Merseburger, Axel ; Scharpf, Marcus ; Kasprzyk, Kathrin ; Schilling, David ; Sievert, Karl‐Dietrich ; Stenzl, Arnulf ; Kruck, Stephan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5032-477ebcd7a386da56a4543a4cba72f718ac72fdfe9ad9f70e660ba26a96cfbca63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Accuracy</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>biomarkers</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cancer</topic><topic>Carcinoma, Renal Cell - blood</topic><topic>Carcinoma, Renal Cell - mortality</topic><topic>Carcinoma, Renal Cell - surgery</topic><topic>CRP</topic><topic>Female</topic><topic>Germany - epidemiology</topic><topic>Humans</topic><topic>Inflammation - blood</topic><topic>Kidney Neoplasms - blood</topic><topic>Kidney Neoplasms - mortality</topic><topic>Kidney Neoplasms - surgery</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging - methods</topic><topic>predictive accuracy</topic><topic>Predictive Value of Tests</topic><topic>Preoperative Period</topic><topic>Prognosis</topic><topic>renal cell cancer</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Studies</topic><topic>Survival Rate - trends</topic><topic>systemic inflammation</topic><topic>threshold</topic><topic>WBC</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bedke, Jens</creatorcontrib><creatorcontrib>Chun, Felix K.‐H.</creatorcontrib><creatorcontrib>Merseburger, Axel</creatorcontrib><creatorcontrib>Scharpf, Marcus</creatorcontrib><creatorcontrib>Kasprzyk, Kathrin</creatorcontrib><creatorcontrib>Schilling, David</creatorcontrib><creatorcontrib>Sievert, Karl‐Dietrich</creatorcontrib><creatorcontrib>Stenzl, Arnulf</creatorcontrib><creatorcontrib>Kruck, Stephan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bedke, Jens</au><au>Chun, Felix K.‐H.</au><au>Merseburger, Axel</au><au>Scharpf, Marcus</au><au>Kasprzyk, Kathrin</au><au>Schilling, David</au><au>Sievert, Karl‐Dietrich</au><au>Stenzl, Arnulf</au><au>Kruck, Stephan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C‐reactive protein does not improve predictive accuracy</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2012-12</date><risdate>2012</risdate><volume>110</volume><issue>11b</issue><spage>E771</spage><epage>E777</epage><pages>E771-E777</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><coden>BJINFO</coden><abstract>What's known on the subject? and What does the study add? White blood cell count and C‐reactive protein are reliable prognostic RCC Biomarkers.Nevertheless, accepted cut‐offs for risk stratifications are missing. Therefore, both parameters were re‐evaluated and multivariable analyses revealed an optimal CRP breakpoint at 0.25 mg/dL to be best to stratify patients at risk of cancer‐specific mortality. However, this CRP‐based prediction added no additional information compared to a clinico‐pathological based model. Objective To re‐evaluate the prognostic and predictive significance of the preoperative white blood cell (WBC) count and C‐reactive protein (CRP) that independently predicts patient prognosis and to determine optimal threshold values for CRP. Patients and Methods From 1996 to 2005, 327 patients with surgery for clear cell renal cell carcinoma were retrospectively evaluated. Cox proportional hazard models were used, adjusted for the effects of tumour stage, size, Fuhrman grade and Karnofsky index, to evaluate the prognostic significance of WBC count and CRP and to identify threshold values. Identified thresholds were correlated with clinicopathological parameters and used to estimate cancer‐specific survival. To prove any additional predictive accuracy of the identified threshold it was compared with a clinicopathological base model using the Harrell concordance index (c‐index). Results In univariable analyses WBC count was a significant prognostic marker at a concentration of 9.5/μL (hazard ratio [HR] 1.83) and 11.0/μL (HR 2.09) and supported CRP values of 0.25 mg/dL (HR 6.47, P &lt; 0.001) and 0.5 mg/dL (HR 7.15, P &lt; 0.001) as potential threshold values. If adjusted by the multivariable models WBC count showed no clear breakpoint, but a CRP value of 0.25 mg/dL (HR 2.80, P = 0.027) proved to be optimal. Reduced cancer‐specific survival was proved for CRP 0.25 mg/dL (median 69.9 vs 92.3 months). Median follow‐up was 57.5 months with 72 (22%) tumour‐related deaths. The final model built by the addition of CRP 0.25 mg/dL did not improve predictive accuracy (c‐index 0.877) compared with the clinicopathological base model (c‐index 0.881) which included TNM stage, grading and Karnofsky index. Conclusions Multivariable analyses revealed that an optimal breakpoint of CRP at a value of 0.25 mg/dL was best to stratify patients at risk of cancer‐specific mortality, but CRP 0.25 mg/dL added no additional information in the prediction model. Therefore we cannot recommend measuring CRP as the traditional parameters of TNM stage, grading and Karnofsky index are already of high predictive accuracy.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23134582</pmid><doi>10.1111/j.1464-410X.2012.11642.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Accuracy
Adolescent
Adult
Aged
Aged, 80 and over
biomarkers
C-Reactive Protein - metabolism
Cancer
Carcinoma, Renal Cell - blood
Carcinoma, Renal Cell - mortality
Carcinoma, Renal Cell - surgery
CRP
Female
Germany - epidemiology
Humans
Inflammation - blood
Kidney Neoplasms - blood
Kidney Neoplasms - mortality
Kidney Neoplasms - surgery
Male
Middle Aged
Neoplasm Staging - methods
predictive accuracy
Predictive Value of Tests
Preoperative Period
Prognosis
renal cell cancer
Reproducibility of Results
Retrospective Studies
Studies
Survival Rate - trends
systemic inflammation
threshold
WBC
Young Adult
title Inflammatory prognostic markers in clear cell renal cell carcinoma – preoperative C‐reactive protein does not improve predictive accuracy
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