Discussion CRP is a standardized and widely used serum indicator of acute phase response in conditions such as acute inflammations, infections, tissue or organ necrosis, and malignancies. Some types of RCCs can induce sys temic inflammations by expressing various cytokines such as IL 1, tumor necrosis factor, and mostly IL 6. In The Right
Control Neratinib Before Time Runs Out vitro experimental studies showed some renal tumors themselves are actually capable of producing IL 6. Furthermore, RCC, especially of the aggressive phenotype, is often accompanied by tumor necrosis. Therefore, tumor status and aggressiveness can be directly reflected by the serum CRP levels of patients with AM RCC. Additionally, in case of other malignancies, CRP had been found to inhibit apoptosis of carcinoma cells, thereby directly regulating tumor cell growth and survival.
In fact, we often encounter cases of AM RCC in which the patients CRP level fluctuates in accordance with disease control and or progression. Several studies have also indicated that elevated CRP is a poor prognostic indicator for RCC. However, almost all the CRP cutoff points reported previously have been single values. These cutoff points range from 1. 0 to 10. 0 mg L and vary widely from study to study, despite the fact that in the majority of studies, the cutoff point was defined on the basis of the normal values. In the current study, we found that over 70% of the patients with AM RCC showed abnormal CRP values, with a relatively wide dynamic range of up to 200 mg L.
In fact, when we initially applied previously reported cutoff points to our patient cohort, we were unable to define any CRP based grouping system that could afford a ra tional assessment of survival risk. In this study, we initially determined the 2 CRP cutoff points 18. 0 and 67. 0 mg L in the nephrectomy patient cohort by means of ROC analysis. We then found that the CRP 3 grouping was a more suitable model for the risk stratifica tion of AM RCC patients because it was also applicable for patients who did not undergo nephrectomy. A number of prognostic parameters have been studied for patients with localized, metastatic, or all stage RCC C. Among the parameters defined for AM RCC, the most well established and validated ones are Memorial Sloan Kettering Cancer Center risk factors and predictors of short survival proposed by the NCCN practice guidelines.
In these models, however, CRP has not been enlisted as a significant fac tor. In our Cox models, we found that the risk factors associated with shorter survivals were high CRP level, low ECOG PS, and high number of metastatic organ sites. On the other hand, Hb and ALP levels were not found to be independent parameters. More over, sex, maximum tumor diameter, LDH and corrected calcium levels did not appear to be statistically signifi cant factors even in the univariate analyses.
As reported previously, nephrectomy provided strong survival advantage for AM RCC patients. The median NSC 136476 survival for the 129 patients who underwent nephrec tomy and the 52 patients who did not undergo nephrec tomy was 23. 9 months and 2. 80 months, respectively. C reactive protein and patient survival From the medical records, we collected data regarding CRP levels at the onset in 143 181 AM RCC patients. The patients exhibited varying serum CRP levels, ran ging from undetectable to 212 mg L, and 103 143 patients had abnormal CRP values. We determined the CRP cutoff point by means of ROC analysis for the cohort of patients who under went nephrectomy. From the ROC analysis, we found 2 reasonable CRP cutoff points, 18. 0 and 67. 0 mg L, accordingly, we classified the patients into nor mal mildly elevated CRP, elevated CRP, and highly elevated CRP groups.
Kaplan Meier analyses revealed statistically signifi cant differences between these 3 groups, and the median overall survival periods were 53. 2, 12. 6, and 4. 20 months in the normal mildly elevated CRP, elevated CRP, and highly elevated CRP groups, respectively. We next applied the same CRP cutoff and grouping system to the AM RCC cohort of patients who did not undergo nephrectomy. We found that the 3 CRP levels defined were again correlated with patient survival and that patients with normal mildly elevated CRP levels clearly showed longer survival periods. The median overall survival periods were 24. 4, 2. 83, and 1. 54 months in the normal mildly elevated CRP, elevated CRP, and highly elevated CRP groups, respectively.
Since patients with highly elevated levels of CRP showed poor prognosis despite the treatment procedures, i. e, nephrectomy or medical treatment only, we compared these 2 groups. Kaplan Meier analysis showed that the 2 groups did not differ statistically. Although the 2 groups differed slightly with respect to patient characteristics and backgrounds, the data suggested that initial nephrectomy did not seem to provide substantial survival advantages for patients with highly elevated CRP levels. CRP as an independent prognostic parameter for AM RCC Lastly, we tested the association of patient survival with CRP values against that with other established clinical and biochemical parameters, including the Memorial Sloan Kettering Cancer Center risk factors.
Survival analysis was performed for 81 patients who underwent nephrectomy and for whom the complete clinical and biochemical data were available. Cox univariate analyses demonstrated that several clin icopathologic parameters, including age. ECOG PS. number of metastatic organ sites. and levels of Hb, ALP, and CRP, showed a statistically significant association with OS. On the other hand, neither LDH nor corrected calcium levels were correlated with survival lengths.