Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy

Current Status of Urinary Biomarkers for Detection and Surveillance of Bladder Cancer.

The standard of care for detection and surveillance of bladder cancer consists of cytology and cystoscopy, but both examinations suffer from many limitations, including issues related to accuracy, invasiveness, and cost. Several noninvasive methods for detection and surveillance of bladder cancer have been developed and urine-based biomarkers seem the most promising. This nonsystematic review critically analyzes the commercially available biomarkers and highlights some upcoming investigational biomarkers. To date, none of these biomarkers has sufficient validation to serve as a reliable alternative to cystoscopy

Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer.

The neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP) are markers of systemic inflammatory response, which have been associated with the prognosis of multiple malignancies, but their relationships with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) have not been well studied yet. We retrospectively reviewed the medical records of 1,117 patients with NMIBC who underwent a transurethral resection of the bladder. Univariable and multivariable competing risk regression models were used to assess the association of preoperative NLR and CRP with disease recurrence and progression to muscle-invasive disease. The median follow-up was 64 months. In total, 360 patients (32.2%) had a high NLR (≥2.5) and 145 (13.0%) had a high CRP (≥5mg/l). On multivariable analyses, a high NLR was associated with both disease recurrence (subhazard ratio [SHR] = 1.27, P = 0.013) and progression (SHR = 1.72, P = 0.007), and high CRP was associated with disease progression (SHR = 1.72, P = 0.031). Adding NLR and CRP to the multivariable model predicting disease progression lead to a relevant change in discrimination (+2.0%). In a subgroup analysis of 300 patients treated with bacillus Calmette-Guerin, both high NLR and high CRP were associated with disease progression (SHR = 2.80, P = 0.026 and SHR = 3.51, P = 0.021, respectively), and NLR was associated with disease recurrence (SHR = 1.46, P = 0.046). There was also an increase in the discrimination of the model predicting progression after bacillus Calmette-Guerin following the inclusion of both markers (+2.4%). In patients with NMIBC, markers of systemic inflammation response are associated with disease recurrence and progression. The inclusion of such markers in prognostic models does enhance their accuracy

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT). A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis. One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS. Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes

The Neutrophil-to-lymphocyte Ratio as a Prognostic Factor for Patients with Urothelial Carcinoma of the Bladder Following Radical Cystectomy: Validation and Meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammatory response has been proposed as a prognostic factor for patients with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). To validate NLR as a prognostic biomarker and to perform a pooled meta-analysis. The NLR was assessed in 4061 patients within 30 days before RC. A systematic review of the literature was undertaken using electronic databases. Associations with overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox models. Hazard ratios (HRs) were pooled in a meta-analysis using random-effects modeling. A high NLR (≥2.7) was associated with advanced pathological tumor stages (p<0.001), lymph node involvement (p<0.001), lymphovascular invasion (p=0.008), and positive soft0tissue surgical margins (p=0.001). In multivariate analyses, a high NLR was independently associated with both OS (HR 1.11, 95% confidence interval [CI] 1.01-1.22; p=0.029) and cancer-specific survival (CSS) (HR 1.21, 95% CI 1.07-1.37, p=0.003). The discrimination of the multivariate models increased by 0.2% on inclusion of NLR. Five studies were included in the meta-analysis. The HR for NLR greater than the cutoff was 1.46 (95% CI 1.01-1.92) for OS and 1.51 (95% CI 1.17-1.85) for CSS. Limitations include the retrospective study design and the lack of standardized follow-up. In patients with UCB treated with RC, a high preoperative NLR is associated with more advanced tumor stage, lymph node metastasis, and worse prognosis. The NLR may be a readily available and useful biomarker for preoperative prognostic stratification. We investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in patients with bladder cancer treated with radical cystectomy. We found that a high NLR is associated with worse oncologic outcomes, suggesting it could play a role in risk stratification

Role of survivin expression in predicting biochemical recurrence after radical prostatectomy: a multi-institutional study.

To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models. Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin. Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent.

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients. Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models. ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively). ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy