Prognostic Value of CRP in Renal Cancer

Abstract & Commentary

By William B. Ershler, MD, Editor

Synopsis: C-reactive protein, an acute phase reactant, is shown to offer significant prognostic information for post nephrectomy patients with renal cell carcinoma. The value of this information will be enhanced if future studies indicate that patients with high levels are more likely to benefit from adjuvant therapy or if it turns out to be a sensitive marker of recurrent disease.

Source: C-Reactive protein is an informative predictor of renal carcinoma-specific mortality. A European study of 313 patients. Cancer. 2007;110:1241-1247.

There is currently an awareness of the importance of inflammatory processes and the proliferative capacity of certain tumors. The association is quite remarkable for patients with renal cell carcinoma (RCC) in whom C-reactive protein (CRP) and erythrocyte sedimentation rate have been associated with survival.1-3 In an effort to compare serum markers of inflammation and standard RCC-specific mortality predictors, Karakiewicz and colleagues performed a retrospective review of 313 patients who were treated by nephrectomy for renal cancer at two European centers. Life-table, Kaplan-Meier, and Cox regression analyses were utilized and data was analyzed in the context of age, gender, TNM stage, tumor size, Fuhrman grade, and histological subtype.

The overall follow-up time ranged from 0.1 to 20.8 years and of the total population, 54 (17.3%) died of RCC. The actuarial mean and median survival were 13.9 and 19.9 years respectively. By univariate analysis, CRP represented the most informative predictor of RCC-specific survival, followed by T-stage and performance status. In multivariate analysis, categorically coded CRP (P = .003), ECOG performance status (P = .001) and M stage (P < .001) achieved independent predictive status. Compared to patients with a baseline CRP level of 0-4 mg/dL, those with values between 4.1 and 23.0 mg/dL had a 5.2 fold increase in RCC-specific mortality, and those with values above 23 mg/dL had an 11-fold increased risk of RCC-specific mortality.

The UCLA Integrated Staging System (UISS), which predicts RCC-specific survival at 2 and 5 years is a commonly used instrument for predicting prognosis for patients with RCC. In the current survey, adding CRP data to UISS was found, in a Cox regression analysis to improve prognostic accuracy by 2.5% at 2 years (85.3%-87.8%, P <.001 and at years>P <.001>

Commentary

CRP is an acute phase protein produced in the liver in response to proinflammatory cytokines. One particularly relevant cytokine in the setting of renal cell carcinoma is IL-6 because renal carcinoma cells have been shown to harbor IL-6 receptors,4 and to proliferate in vitro when exposed to IL-6.4,5 Furthermore, serum IL-6 levels, like CRP, have been shown to correlate with RCC survival.6 In fact, renal carcinoma cells have been shown to secrete IL-6 producing an autocrine growth effect in vitro7; a feature that has been speculated to be important in the progression of disease, at least in some patients with this disease.8

Thus, it comes as no surprise that CRP is of prognostic importance in RCC. The clinical utility of this observation remains to be determined. It is notable that currently two agents (sorafenib and sunitinib) are being tested in three different clinical trials for post nephrectomy, adjuvant treatment of RCC. It may ultimately prove that pretreatment CRP levels will prove a useful indicator of those who are likely to benefit from such treatment. Furthermore, the value of serial CRP measures to assess early recurrence would seem a worthwhile investigation.

References

1. Fujikawa K, et al. J Urol. 1999;162(6):1934-1937.

2. Ito K, et al. Int J Urol. 2006;13(11):1365-1370.

3. Komai Y, et al. BJU Int. 2007;99(1):77-80.

4. Costes V, et al. J Clin Pathol. 1997;50(10):835-840.

5. Horiguchi A, et al. Kidney Int. 2002;61(3):926-938.

6. Blay JY, et al. Cancer Res. 1992;52(12):3317-3322.

7. Alberti L, et al. Int J Cancer. 2004;111(5):653-661.

8. Sakai A, et al. N Engl J Med. 1991;324(26):1893-1894.