Objective• To validate high-sensitivity C-reactive protein (hs-CRP) serum levels as an independent marker for disease-free survival (DFS) in clinically localised clear cell renal cell carcinoma (ccRCC). Patients and Methods• In all, 403 consecutive patients with clinically localised (T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled.• Preoperative serum levels of hs-CRP were evaluated as both a continuous and categorical variables.• Associations with clinical (age, gender) and pathological variables (T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal-Wallis tests.• Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy (PA) was assessed with Harrell's C-index. Results• The mean hs-CRP level was 1.32 mg/dL. The hs-CRP levels were associated with T classification (P = 0.05), high-grade disease (P < 0.001) and tumour necrosis (P = 0.003).• After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs-CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015).• The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence.• These categorically coded hs-CRP levels were identified as independent prognostic factors in multivariable analyses (P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' (SSIGN) score. Conclusions• This study validates preoperative serum hs-CRP levels as independent prognostic factor after surgery for localised ccRCC.• Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials.

ObjectiveTo assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers. Patients and MethodsWe analysed 867 patients, who underwent radical or partial nephrectomy for RCC between 2002 and 2012. Preoperative total cholesterol levels were determined in serum using colorimetric analysis (CHOD-PAP method). The association with cancer-specific survival (CSS) was assessed with Cox models. Discrimination was quantified with the C-index. The median follow-up was 52 months. ResultsThe median (interquartile range) serum cholesterol was 195 (166-232) mg/dL. Decreasing serum cholesterol was associated with more advanced T, N and M stages (P < 0.001), higher grades (P = 0.001) and presence of tumour necrosis (P = 0.002). Continuously coded cholesterol was associated with CSS in both univariable (hazard ratio [HR] 0.87, P < 0.001) and multivariable analyses (HR 0.93, P = 0.001). The discrimination of a multivariable base model increased significantly from 88.3% to 89.2% following inclusion of cholesterol (P = 0.006). In patients with clinically localised disease (T1-3N0/+M0), cholesterol remained associated with CSS in multivariable analysis (HR 0.90, P = 0.002) and increased the discrimination from 74.6% to 76.9% (P = 0.002). ConclusionsPreoperative serum cholesterol is an independent prognostic factor for patients with RCC, with lower levels being associated with worse survival. Its use increases the discrimination of established prognostic factors. As cholesterol is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice. The biological rationale underlying this association remains to be clarified.

PurposeTo evaluate the impact of presenting symptoms on survival in a contemporary series of patients with renal cell carcinoma (RCC).Materials and MethodsWe prospectively recorded data on the presenting symptoms, pathology, and RCC-specific survival of 633 consecutive RCC patients who underwent surgery between 2003 and 2012.ResultsFour hundred thirty-three RCCs (68%) were incidental, 111 (18%) were associated with local symptoms, and 89 (14%) were associated with systemic symptoms. Among those with incidental RCC, 317 patients (73%) were completely asymptomatic and 116 patients (27%) presented with symptoms not related to the tumor. During a median follow-up interval of 40 months (interquartile range: 39 to 69 months), 77 patients died from RCC. In univariate analyses, symptom classification was significantly associated with RCC-specific survival (p<0.001). Patients with incidental RCC and unrelated symptoms tended to have worse prognosis than did patients who were completely asymptomatic, although this difference was not statistically significant (p=0.057). The symptom classification was associated with advanced TNM stages (p<0.001) and grade (p<0.001).ConclusionsThis study confirms that presenting symptoms are associated with tumor characteristics and survival. The majority of RCCs are diagnosed incidentally in patients without any symptoms or with symptoms not related to RCC. Patients in the latter group tend to have a worse prognosis than do patients who are completely asymptomatic. With the increasing number of incidentally diagnosed RCCs, substratification of patients with incidental tumors may be prognostically relevant.