Mihai Dorin Vartolomei

Easily Available Blood Test Neutrophil-To-Lymphocyte Ratio Predicts Progression in High-Risk Non-Muscle Invasive Bladder Cancer

Abstract Introduction: The inflammatory response surrounding the tumour has a major importance in the oncologic outcome of bladder cancers. One marker proved to be useful and accessible is NLR (neutrophil-to-lymphocyte ratio). The objective of the study was the analysis of NLR as a prognostic factor for recurrence and progression in pT1a and pT1b bladder cancers. Material and Methods: Retrospective study, with 44 T1a/T1b bladder cancer patients. Each patient underwent transurethral resection. NLR was considered altered if higher than 3, average follow-up period was of 18 months. Results: The mean age of the patients included was 73 years (IQR 64 - 77). Most of the patients had NLR<3 (30 patients). In total 29/44 (65.9 %) patients presented recurrence and 15/44 (34.1 %) patients were identified with T2 or higher stage progression during the follow-up period (average 18 months).We found no statistically significant association between NLR>3 and other clinic and pathologic factors. Progression-free survival (PFS) Kaplan-Meier analysis showed a lower PFS in the NLR>3 group, with a p=0.001 value. A total of 64.3% of patients had shown progression in the NLR>3 group and 20% in the NLR<3 group. Mean NLR was 2.67 (IQR 1.88-3.5); 2.50 (IQR 1.89-2.87) in patients that did not present any progression during the follow-up and 3.20 (IQR 1.73-5.80) in those with progression (p=0.09), ROC 0.655. Mean NLR was 2.14 (IQR 1.61-2.77) in patients that did not experience a recurrence during the follow-up and 2.76 (IQR 2.1-4.31) in those with recurrence, ROC 0.671 (p=0.06). Multivariable Cox regression analyses showed that stage T1b and NLR represent independent prognostic factors for PFS. Conclusion: High Neutrophil-to-Lymphocyte ratio retained a statistically significant value, as an independent prognostic factor for bad prognosis of T1 bladder tumors. NLR represents a biomarker that could support a clinical decision making in case of high-risk on-muscle invasive bladder cancer.

Is neutrophil-to-lymphocytes ratio a clinical relevant preoperative biomarker in upper tract urothelial carcinoma? A meta-analysis of 4385 patients

BackgroundPreoperative blood-based inflammatory biomarkers have been suggested to improve staging and prognostication in patients with upper-tract urothelial carcinoma (UTUC). Neutrophil-to-lymphocyte ratio (NLR) is the most studied blood-based biomarker. NLR is an indicator of systemic inflammation and has been shown to be associated with a poor prognosis in various malignancies. The aim of this study was to analyze the current evidence regarding the prognostic significance of preoperative NLR in patients undergoing radical nephroureterectomy (RNU) for UTUC to assess its prognostic potential.Materials and methodsA systematic search of Web of Science, Medline/PubMed and Cochrane library was performed on the 1st of October, 2017. Studies were deemed eligible if they compared patients with high NLR before surgical treatment for UTUC to patients with low NLR to determine its predictive value for survival using multivariable logistic regression analysis. We performed a formal meta-analysis for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS).ResultsNine studies including a total of 4385 patients assessing the importance of NLR were included in this meta-analysis. The cut-off NLR varied in the eligible studies ranging from 2 to 3. Increased pretreatment NLR predicted OS (pooled HR 1.64 95% CI; 1.23–2.17), RFS (pooled HR 1.60 95% CI; 1.16–2.20) and CSS (pooled HR 1.73 95% CI; 1.23–2.44) in multivariable analyses.ConclusionIn this meta-analysis, preoperative blood-based NLR is associated with worse prognosis in patients who underwent RNU for UTUC. NLR could be used to improve clinical decision making regarding RNU vs. kidney-sparing surgery, extent of lymphadenectomy, perioperative systemic therapy and follow-up schedule.

Prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) in patients with non–muscle-invasive bladder cancer (NMIBC): A systematic review and meta-analysis

OBJECTIVE The aim of this study was to summarize and analyze the current evidence regarding the prognostic and predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients undergoing transurethral resection of bladder tumors (TURBT) for non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS A systematic search of Web of Science, Medline/PubMed, Google Scholar, and Cochrane library was performed on the 1st of March, 2018. Studies were deemed eligible if they compared NMIBC patients with high vs. low NLR before TURBT to determine its value for prognosticating disease recurrence and progression using multivariable analysis. We performed a formal meta-analysis for both recurrence-free (RFS) and progression-free survival (PFS). RESULTS Six studies encompassing 2,298 patients (477 [20.7%] females) assessed the prognostic value of NLR in NMIBC patients treated with TURBT. NLR predicted worse RFS (pooled HR = 1.78; 95% CI: 1.32-2.4, P<0.001) and PFS (pooled HR = 2.14; 95% CI: 1.59-2.87, P<0.001). In 4 studies encompassing 599 patients, high pretreatment NLR was associated with decreased RFS (pooled HR = 2.31; 95% CI: 1.27-4.22, P = 0.006) and in 3 of them high pretreatment NLR was associated with decreased PFS (pooled HR = 2.54; 95% CI: 1.36-4.71, P = 0.003) in high-risk NMIBC patients treated with BCG. CONCLUSION In this meta-analysis, peripheral blood levels of NLR were associated with an increased risk of disease recurrence and progression in patients who underwent TURBT for NMIBC. Furthermore, NLR was an independent predictor of disease recurrence and progression in NMIBC treated with BCG patients. NLR could be used to improve clinical decision-making regarding treatment and follow-up scheduling.

Outcomes of robot-assisted simple enucleation of renal masses: A single European center experience

Abstract The aim of this study was to assess the ability of pre-and intraoperative parameters, to predict the risk of perioperative complications after robot-assisted laparoscopic simple enucleation (RASE) of renal masses, and to evaluate the rate of trifecta achievement of this approach stratifying the cohort according to the use of ischemia during the enucleation. From April 2009 to June 2016, 129 patients underwent RASE at our Institution. We stratified the procedures in 2 groups: clamping and clamp-less RASE. After RASE, all specimens were retrospectively reviewed to assess the surface–intermediate–base (SIB) scoring system. Patients were followed-up according to the European Association of Urology guidelines recommendations. All pre-, intra-, and postoperative outcomes were prospectively collected in a customized database and retrospectively analyzed. A total of 112 (86.8%) patients underwent a pure RASE and 17 (13.2%) had a hybrid according to SIB classification system. The mean age was 61.17 years. In 21 patients (16.3%), complications occurred, 13 (61.9%) were Clavien 1 and 2, while 8 were Clavien 3a and b complications. Statistical significant association with complications was found in patients with American Society of Anestesiology (ASA) score 3 (44.5%, P = .04), longer mean operative time (OT) 195 versus 161.36 minutes (P =.03), mean postoperative hemoglobin (Hb) 10.1 versus 11.8 (P <.001), and mean &Dgr;Hb 3.59 versus 2.18 (P <.001). In multivariate logistic regression, only longer OT and &Dgr;Hb were statistical significant predictive factors for complications. In sub-group analysis, clamp-less RASE was safe in terms of complications (14.1%), positive surgical margins (1.3%), and mid-term local recurrence (1.3%). Although in this approach there is higher EBL (P = .01), this had no impact on &Dgr;Hb (P = .28). A clamp-less approach was associated with a higher rate of SIB 0 (71.8% vs 51%, P = .02), higher trifecta achievement (84.6% vs 62.7%, P = .004), and better impact on serum creatinine (mean 0.83 vs 0.91, P = .01). RASE of renal tumors is a safe technique with very good postoperative outcomes. Complication rate is low and associated with ASA score >3, longer OT, and &Dgr;Hb. RASE is suitable for the clamp-less approach, which allows to perform easier the pure enucleation (SIB 0) and to obtain higher rates of trifecta outcomes.

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer

PurposeThe body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC).MethodsA total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette–Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression.ResultsAfter re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9.ConclusionsThe BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

The impact of moderate wine consumption on the risk of developing prostate cancer

Objective To investigate the impact of moderate wine consumption on the risk of prostate cancer (PCa). We focused on the differential effect of moderate consumption of red versus white wine. Design This study was a meta-analysis that includes data from case–control and cohort studies. Materials and methods A systematic search of Web of Science, Medline/PubMed, and Cochrane library was performed on December 1, 2017. Studies were deemed eligible if they assessed the risk of PCa due to red, white, or any wine using multivariable logistic regression analysis. We performed a formal meta-analysis for the risk of PCa according to moderate wine and wine type consumption (white or red). Heterogeneity between studies was assessed using Cochrane’s Q test and I2 statistics. Publication bias was assessed using Egger’s regression test. Results A total of 930 abstracts and titles were initially identified. After removal of duplicates, reviews, and conference abstracts, 83 full-text original articles were screened. Seventeen studies (611,169 subjects) were included for final evaluation and fulfilled the inclusion criteria. In the case of moderate wine consumption: the pooled risk ratio (RR) for the risk of PCa was 0.98 (95% CI 0.92–1.05, p=0.57) in the multivariable analysis. Moderate white wine consumption increased the risk of PCa with a pooled RR of 1.26 (95% CI 1.10–1.43, p=0.001) in the multi-variable analysis. Meanwhile, moderate red wine consumption had a protective role reducing the risk by 12% (RR 0.88, 95% CI 0.78–0.999, p=0.047) in the multivariable analysis that comprised 222,447 subjects. Conclusions In this meta-analysis, moderate wine consumption did not impact the risk of PCa. Interestingly, regarding the type of wine, moderate consumption of white wine increased the risk of PCa, whereas moderate consumption of red wine had a protective effect. Further analyses are needed to assess the differential molecular effect of white and red wine conferring their impact on PCa risk.

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study

Introduction: The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC). Patients and Methods: The study period was from January 2002 to December 2012. A total of 1,046 patients with primary T1 HG/G3 and who had non-muscle invasive BC (NMIBC) on re-TUR followed by adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with maintenance were included. Endpoints were time to disease recurrence, progression, and overall and cancer-specific death. Results: A total of 257 (24.6%) patients had residual T1 HG/G3 tumors. The presence of concomitant carcinoma in situ, multiple and large tumors (> 3 cm) at first TUR were associated with residual T1 HG/G3. Five-year recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were 17% (CI 11.8–23); 58.2% (CI 50.7–65); 73.7% (CI 66.3–79.7); and 84.5% (CI 77.8–89.3), respectively, in patients with residual T1 HG/G3, compared to 36.7% (CI 32.8–40.6); 71.4% (CI 67.3–75.2); 89.8% (CI 86.6–92.3); and 95.7% (CI 93.4–97.3), respectively, in patients with NMIBC other than T1 HG/G3 or T0 tumors. Residual T1 HG/G3 was independently associated with RFS, PFS, OS, and CSS in multivariable analyses. Conclusions: Residual T1 HG/G3 tumor at re-TUR confers worse prognosis in patients with primary T1 HG/G3 treated with maintenance BCG. Patients with residual T1 HG/G3 for primary T1 HG/G3 are very likely to fail BCG therapy alone.

Prognostic value of concomitant carcinoma in situ in the radical cystectomy specimen: A systematic review and meta-analysis

Purpose: We investigated the prognostic impact of concomitant carcinoma in situ in radical cystectomy specimens. Materials and Methods: We performed a systematic review and meta-analysis using MEDLINE®, Scopus®, Web of Science™ and The Cochrane Library to identify eligible studies published until October 2017. Studies were eligible for analysis if they compared patients with concomitant carcinoma in situ in radical cystectomy specimens for bladder cancer to patients without concomitant carcinoma in situ to determine its value to prognosticate overall mortality, recurrence-free survival, cancer specific mortality and ureteral involvement using multivariable analysis. The protocol for this systematic review was registered in PROSPERO (Prospective Register of Systematic Reviews, CRD42018086539) and is available in full on the University of York website. Results: Overall 23 studies published between 2006 and 2017 including a total of 20,647 patients were selected for the systematic review and meta-analysis. Concomitant carcinoma in situ was reported in 39.4% of radical cystectomy specimens. In studies analyzing all patients the presence of concomitant carcinoma in situ was not associated with overall mortality (pooled HR 0.92, 0.77–1.10), recurrence-free survival (pooled HR 1.06, 0.99–1.13) or cancer specific mortality (pooled HR 1.00, 0.93–1.07). It was associated with ureteral involvement (pooled OR 4.51, 2.59–7.84). On subanalysis of studies restricted to patients with organ confined bladder cancer at radical cystectomy concomitant carcinoma in situ was associated with worse recurrence-free survival (pooled HR 1.57, 1.12–2.21) and cancer specific mortality (pooled HR 1.51, 1.001–2.280). Conclusions: Concomitant carcinoma in situ is significantly associated with ureteral involvement in patients treated with radical cystectomy. In patients with organ confined disease concomitant carcinoma in situ in the radical cystectomy specimen is a prognosticator of recurrence-free survival and cancer specific mortality.

The Role of Urologist

The urologist will have a key-role in the prevention and management of bladder cancer (BC), also in the future. This chapter focuses on the possible changes in whom the urologist will be involved. First subchapter discusses the nature of BC as a preventable disease. Cigarette smoking is the most preventable cause of BC and more efforts should be done to encourage smoking cessation among general population and newly diagnosed BC patients. Second subchapter focuses on early detection of BC. In future, improved definition of high risk populations suited for screening together with the development of integrated multi-markers models may improve early detection of urothelial cancer. The third subchapter is dedicated to intravesical therapies and how can be done best in the management of BC. BCG is still the best adjuvant treatment for intermediate and high-risk NMIBC, for patients who experience BCG failure, to date; only Valrubicin is FDA approved therapy. Forth subchapter is focused on precision medicine and immunotherapy for BC patients. PD-1/PD-L1 checkpoints blockades are approved therapies in second line metastatic BC and in first line cisplatin-ineligible BC because of their high efficacy and tolerability. Knowledge of the side effects and experience in their management is essential to optimal patient care.

Predictors of Residual T1 High Grade on Re-Transurethral Resection in a Large Multi-Institutional Cohort of Patients with Primary T1 High-Grade/Grade 3 Bladder Cancer

The aim of this multi-institutional study was to identify predictors of residual high-grade (HG) disease at re-transurethral resection (reTUR) in a large cohort of primary T1 HG/Grade 3 (G3) bladder cancer patients. A total of 1155 patients with primary T1 HG/G3 bladder cancer from 13 academic institutions that underwent a reTUR within 6 weeks after first TUR were evaluated. Logistic regression analysis was performed to assess the association of predictive factors with residual HG at reTUR. Residual HG cancer was found in 288 (24.9%) of patients at reTUR. Patients presenting residual HG cancer were more likely to have carcinoma in situ (CIS) at first resection (p<0.001), multiple tumors (p=0.02), and tumor size larger than 3 cm (p=0.02). Residual HG disease at reTUR was associated with increased preoperative neutrophil-to-lymphocytes ratio (NLR) (p=0.006) and body mass index (BMI)>=25 kg/m2. On multivariable analysis, independent predictors for HG residual disease at reTUR were tumor size >3cm (OR = 1.37; 95% CI: 1.02-1.84, p=0.03), concomitant CIS (OR 1.92; 95% CI: 1.32-2.78, p=0.001), being overweight (OR= 2.08; 95% CI: 1.44-3.01, p<0.001) and obesity (OR 2.48; 95% CI: 1.64-3.77, p<0.001). A reTUR in high grade T1 bladder cancer is mandatory as about 25% of patients, presents residual high grade disease. Independent predictors to identify patients at risk of residual high grade disease after a complete TUR include tumor size, presence of carcinoma in situ, and BMI >=25 kg/m2.