Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry

Background : To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). Patients and Methods : We queried the International Marker Consortium for Renal Cancer (INMARC) database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (ccRCC), chromophobe (chRCC), papillary (pRCC), and variant histology RCC (vhRCC); and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression (MLR) were fitted to elucidate predictors of outcomes. Results : 3,902 patients (high CRP n=1,266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, p<0.001), ccRCC (HR 2.69, p<0.001), chRCC (HR 3.99, p<0.001), pRCC (HR 1.76, p=0.009) and vhRCC (HR 2.97, p=0.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, p<0.001), chRCC (HR 6.16, p=0.003) and pRCC (HR 2.29, p=0.011), while in vhRCC was not (p=0.27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, p=0.013), while in chRCC (p=0.33), pRCC (p=0.34) and vhRCC (p=0.52) was not. On MLR CRP was a predictor of pRCC (OR 1.003, p=0.002), while decreasing CRP was associated with benign tumors (OR 0.994, p=0.048). Conclusion : Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.