We read with great interest the paper by Bedke et al. , which showed that using C-reactive protein (CRP) as a biomarker, with 0.25mg/dL as a threshold, did not improve predictive accuracy in a clear-cell RCC model. In certain clinical settings where traditional variables, such as TNM stage, grading and performance status are assessed objectively, a prognostic model for clear-cell RCC consisting of such variables would be helpful, especially if it did not require additional variables such as biomarker measurements and blood data.
The model presented by Bedke et al. includes several subjective variables (Fuhrman grade and performance status). It is worth noting that the evaluation of these subjective variables might be affected by interobserver variation . By contrast, CRP is a serum variable which can be measured objectively. If the subjective variables in the Bedke model could be replaced with objective ones that are routinely available at most institutions, this predictive model would become more consistent and more easily generalizable. We have shown that the predictive model known as TNM-C, which includes CRP instead of subjective variables such as Fuhrman nuclear grade, yields an acceptable level of predictive ability .
Yet should the utility of a biomarker be evaluated based only on its discriminative accuracy? Although one of the main motivations for identifying biomarkers is the possibility of incorporating them into prognostic models, biomarkers should be evaluated not only for their utility in discrimination but also with regard to other statistical metrics.
Bedke et al.  investigated the prognostic impact of CRP as a biomarker, but only in preoperative settings and using a single cohort without external validation, although many studies have shown that CRP is a powerful predictor of outcomes in RCC . Furthermore, many investigators have reported that the availability of CRP data is linked to improved RCC outcomes in a variety of clinical settings. Several papers have indicated that, in advanced disease states, CRP still has prognostic impact in a postoperative setting . Moreover, CRP is useful not only as a static indicator of prognosis, but also as an indicator of change: measuring dynamic changes in CRP concentration permits the observation of the pharmacological response to therapeutic intervention in RCC . Serial measurements of CRP concentration can be used to monitor the response to therapy at any time during treatment, even during surgery or systemic cytokine therapy. These findings show that CRP can serve as a biomarker for RCC in daily practice .
Although a single study showed that CRP did not add significant prognostic value to an established prognostic model, the significance of CRP cannot be dismissed in the clinical treatment of RCC.
Junichiro Ishioka, Kazutaka Saito and Kazunori Kihara
Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan
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