Elevated preoperative C-reactive protein is associated with renal functional decline and non-cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC).

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.

Comparison of renal functional outcomes of active surveillance and partial nephrectomy in the management of oncocytoma.

PURPOSE: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. METHODS: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m2). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival. RESULTS: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m2, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m2, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001). CONCLUSION: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.

Association of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and De Ritis ratio with mortality in renal cell carcinoma: A multicenter analysis.

Background: Several markers of inflammation have been associated with oncologic outcomes. Prognostic markers are not well-defined for renal cell carcinoma (RCC). We sought to investigate the association of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis ratio with mortality in RCC. Methods: Multi-center retrospective analysis of patients undergoing surgery for RCC. Primary outcome of interest was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM) and cancer-specific mortality (CSM). Elevated NLR was defined as ≥2.27, elevated PLR as ≥165, and elevated De Ritis ratio as ≥ 2.72. Multivariable cox regression analysis (MVA) was conducted to elucidate risk factors for primary and secondary outcomes, and Kaplan-Meier analysis (KMA) was used to evaluate survival outcomes comparing elevated and non-elevated NLR, PLR, and De Ritis ratio. Results: 2656 patients were analyzed (874 patients had elevated NLR; 480 patients had elevated PLR and 932 patients had elevated De Ritis). Elevated NLR was a significant predictor of ACM (HR 1.32, 95% CI: 1.07-1.64, p=0.003) and NCM (HR 1.79, 95% CI: 1.30-2.46, p<0.001) in MVA. Elevated De Ritis was a significant predictor of ACM (HR 2.04, 95% CI: 1.65-2.52), NCM (HR 1.84, 95% CI: 1.33-2.55, p<0.001), and CSM (HR 1.97, 95% CI:1.48-2.63, p<0.001). KMA revealed significant difference in 5-year overall survival (OS) (48% vs. 68%, p<0.001), non-cancer survival (NCS) (69% vs. 87%, p<0.001), and cancer-specific survival (CSS) (60% vs. 73%, p<0.001) for elevated versus non-elevated NLR. For PLR, there was a difference in 5-year OS (51% vs. 61%, p<0.001) and CSS (60% vs. 73%, p<0.001) with KMA. Conclusions: Elevated NLR was independently associated with worse ACM and NCM, while elevated De Ritis was predictive for CSM in addition to ACM and NCM. These differences may be useful in refining risk stratification with respect to cancer-related and non-cancer mortality in RCC patients and deserve further investigation.