Only recently, Saito et al.  presented a study including 130 patients suggesting for the first time that elevated CRP is associated with a poor prognosis in patients with UUT-UC. The authors recommended stratifying patients according to the CRP cut-off values of 5.0 mg/l. In this study, we could confirm that a CRP value of >5.0 mg/l was significantly associated with muscle invasive disease (pT≥2), lymph node metastasis, distant metastasis and poor tumour differentiation. Furthermore, a high CRP value was associated with poor cancer specific survival in patients undergoing resection for UUT-UC. These results confirmed the impact of circulating CRP levels on the staging and prognosis of patients with UUT-UC.
Saito et al.  were able to identify an elevated CRP and lymph node invasion as an independent preoperative risk factor for disease-specific death. In this study multivariate analysis including age, sex, histological subtype, tumour stage, and differentiation identified the presence of lymph node and/or distant metastasis and both an elevated CRP value and age, at least as continuous metric parameters, as independent predictors for CSS in patients with UUT-UC.
As biomarkers in body fluids offer the opportunity for more objective and reproducible measurement prior to tumour surgery, the use of CRP as a worldwide well-standardized parameter, should not be underestimated. Rather than tumour tissue-based factors, it can easily be implemented as a prognostic factor in addition to tumour stage and grade, to more accurately stratify patients with UUT-UC. However, as CRP is a not a specific biomarker its use is limited in patients with other diseases in which CRP might be elevated, e.g. inflammatory or cardiovascular disease.
Systemic inflammatory response is of considerable importance in the relationship between the tumour, the host and outcome in patients with cancer. Elevation of the serum CRP level can be explained as part of a paraneoplastic syndrome . It is likely that the association with muscle invasive disease among patients with high serum CRP levels may be due to tumor spread that cannot be detected either by routine imaging studies or by pathologic examinations.
However, the mechanism of high CRP in patients with solid tumors, e.g. urogential or gastrointestinal cancer, has not been determined yet. Several explanations have been proposed such as that CRP could directly impair immune functions [22–24] allowing unrestrained tumour growth. Alternatively, CRP is a component of the acute- phase response mainly induced by interleukin-6, and thus has the potential to enhance or inhibit the proliferation of carcinoma cells. Therefore, an elevated CRP might indicate tumours capable of producing significant amounts of proinflammatory cytokines, in particular interleukin-6 [25, 26].
In genito-urinary malignancies, interleukin-6 functions as an autocrine growth factor for renal cell and prostate cancer [27–30]. Previously, we reported that a high preoperative serum CRP level is an independent predictor of poor survival in patients with renal cell cancer . Trichopoulos et al.  revealed that elevated CRP can be related to a higher risk of developing bladder cancer. Experimental studies have shown that malignant urothelial cells acquire an additional growth advantage over benign cells by producing interleukin-6 . These findings support the view that a systemic inflammatory response of the host indicates an aggressive nature of UUT-UC.
There are several limitations in our study that need to be acknowledged. The major limitation of this study is its retrospective design therefore the drawn conclusions have to be treated with reservation and need to be confirmed in prospective settings. Further limitations are the relative small number of patients and the short mean follow-up of only 28 month. In addition, surgical series have obvious inherent and selection biases as they only evaluate patients undergoing surgery and patient’s deemed nonsurgical candidates, for metastatic disease or other reasons, are not included. Finally, our cohort included significantly more patients with renal pelvis cancer than with UC of the ureter, this imbalance might have biased our analysis.