DISCUSSION


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To the best of our knowledge, the present meta-analysis is the first and most comprehensive study to systematically analyze the prognostic value of pretreatment serum albumin in RCC patients. It is also the first meta-analysis to expound the relationship between serum albumin and the prognosis of patients with solid tumors. According to our final results, there was a significant correlation of low pretreatment serum albumin levels with poor survival of RCC patients, with a combined HR of 2.46 (95% CI 1.92–3.13) for OS, 2.22 (95% CI 1.87–2.64) for CSS, and 1.75 (95% CI 1.28–2.38) for RFS/PFS. Generally, in the subgroup analysis, decreased pretreatment serum albumin was an important prognostic marker in RCC patients, regardless of tumor type, analysis type, cutoff value, and HR-obtaining method, except for OS in all-stage RCC. Considering the lower sample size of the only subgroup with a different result (two studies involving 672 patients), we can ignore the inconsistent result to some extent.

Pretreatment serum albumin is closely related to the prognosis of RCC and other malignant tumors; the underlying reasons for this are still speculative, but explanations involving nutrition and inflammation have been widely recognized. The initiation and progression of cancer are often accompanied by malnutrition and chronic inflammation, which often develop into tumor cachexia and accelerate the deterioration of cancer patients. Malnutrition in cancer patients is usually caused by loss of appetite and malignant tumor depletion, which is reflected in hypoalbuminemia and pitting edema. The systematic inflammatory response in cancer patients also alters the concentration of serum albumin. Under inflammatory conditions, activated proinflammatory cytokines, including tumor necrosis factor, and interleukin -1, -6, and -8, inhibit the ability of liver cells to generate albumin.8,33,34 In addition, the TNF generated by cancer cells increases the permeability of capillaries, which results in the direct loss of albumin from the circulatory system.35 Furthermore, with the malignant progress of the tumor, development of micrometastases in the liver impairs liver function and reduces the synthesis of albumin.8,36 Therefore, the lower the level of serum albumin, the worse the prognosis of cancer patients, and consequently, pretreatment serum albumin is an effective prognostic indicator for cancer patients.

Serum albumin is a convenient and economic prognostic indicator for RCC patients; the concentration of serum albumin can be easily monitored by biochemical examination at any time. The reduction of serum albumin concentration in cancer patients not only demonstrates the deterioration of their nutritional condition, but also indicates a poor prognosis. Therefore, clinical personnel can conduct risk stratification on cancer patients on the basis of the concentration of pretreatment serum albumin, in order to individualize treatment. However, as a prognostic indicator in RCC patients, serum albumin does have some limitations. For example, in the overhydrated state or with other disease processes, serum albumin may not indicate the true nutritional status, so its prognostic value in RCC patients will be disturbed.37 Meanwhile, the level of serum albumin is a blood index, which may be slightly affected by diet and other nontumor-related factors. Nevertheless, without the interference of these factors, pretreatment serum albumin is of great prognostic value in RCC patients.

There were several limitations in this study; first, only 17 studies and 6,447 patients were included in our meta-analysis, ie, there was a relatively small sample size. Second, there was heterogeneity between the studies that may have been caused by differences in research design, basic features of the patients, cutoff values for pretreatment serum albumin, therapeutic methods, and follow-up periods. Moreover, owing to the lack of sufficient data, the associations between pretreatment serum albumin and other important clinical characteristics were not explored.

CONCLUSION

In conclusion, this meta-analysis clarified that a decreased pretreatment serum albumin level implied a poor prognosis for RCC patients. The level of pretreatment serum albumin is a convenient and economic prognostic indicator, and can be monitored for risk stratification and treatment individualization in RCC patients. Considering the limitation of the present analysis, further prospective multicenter studies should be carried out to confirm our findings.


Zhen Chen,1,* Yingjie Shao,2,* Kun Wang,1 Wei Cao,1 Yulong Xiong,1 Rongzu Wu,1 Shicheng Luo,1Xianlin Xu,3,* Xiaozhou He1,*

1Department of Urology, The Third Affiliated Hospital of Soochow University, 2Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, 3Department of Urology, Sir Run Run Shaw Hospital, Third Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

*These authors contributed equally to this work 


Acknowledgments

This work was supported by the National Science Foundation of Jiangsu Province (Grant no BK20150251).

Disclosure

The authors report no conflicts of interest in this work.

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Source: OncoTargets and Therapy
Originally published October 28, 2016.