Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo evaluate the prognostic effect of concomitant variant histology (CVH) on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Materials and methodsData on 417 patients with UTUC treated with radical nephroureterectomy without preoperative adjuvant therapy were retrospectively reviewed with a focus on CVH. Clinicopathological features and prognostic factors were compared between patients with pure UTUC and patients with UTUC with CVH. The primary end points were cancer-specific survival (CSS), disease recurrence-free survival (DFS), and overall survival (OS).ResultsUTUC with CVH was present in 90 (21.6%) of 417 patients. At a median follow-up of 26 months, 153 (36.7%) had died of UTUC, 161 (38.6%) had experienced a relapse, and 176 (42.2%) had died of other causes. UTUC with CVH was significantly associated with advanced tumor stage, high tumor grade, tumor diameter, lymphovascular invasion, lymph node metastasis, positive surgical margins, and tumor architecture compared with pure UTUC (all P<0.01). The estimated 5-year CSS, DFS, and OS rates were 64.9%, 61.1%, and 62.1%, respectively, in the pure UTUC group, compared with 36.3%, 34.3%, and 26.5%, respectively, in the UTUC with CVH group (P<0.001). Multivariate analysis demonstrated that CVH was an independent predictor of CSS (hazard ratio [HR] = 1.594; 95% CI: 1.125–2.259; P = 0.009), DFS (HR = 1.549; 95% CI: 1.077–2.152; P = 0.017), and OS (HR = 1.685; 95% CI: 1.212–2.343; P = 0.002).ConclusionsApproximately one-fifth of the specimens of patients with UTUC were observed to exhibit CVH. CVH was an independent prognostic factor for CSS, DFS, and OS in patients with UTUC on both univariate and multivariate analyses. Genitourinary pathologists should look for potential CVH components in UTUC specimens and report this in routine pathological practice. The presence of CVH should identify patients as candidates for consultation regarding early adjuvant therapy and intensive surveillance protocols.     

Impact of the controlling nutritional status (CONUT) score on perioperative morbidity and oncological outcomes in patients with bladder cancer treated with radical cystectomy

Introduction and objectivesTo evaluate the impact of the Controlling Nutritional Status (CONUT) score on perioperative morbidity and oncological outcomes of bladder cancer (BC) patients treated with radical cystectomy (RC).Materials and MethodsWe retrospectively analyzed a multi-institutional cohort of 347 patients treated with RC for clinical-localized BC between 2005 and 2019. The CONUT-score was defined as an algorithm including serum albumin, total lymphocyte count, and cholesterol. Multivariable logistic regression analyses were performed to evaluate the ability of the CONUT-score to predict any-grade complications, major complications and 30 days readmission. Multivariable Cox’ regression models were performed to evaluate the prognostic effect of the CONUT-score on recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS).ResultsA cut-off value to discriminate between low and high CONUT-score was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.72 hence high CONUT-score was defined as ≥3 points. Overall, 112 (32.3%) patients had a high CONUT. At multivariable logistic regression analyses, high CONUT was associated with any-grade complications (OR 3.58, P = 0.001), major complications (OR 2.56, P = 0.003) and 30 days readmission (OR 2.39, P = 0.01). On multivariable Cox' regression analyses, high CONUT remained associated with worse RFS (HR 2.57, P < 0.001), OS (HR 2.37, P < 0.001) and CSS (HR 3.52, P < 0.001).ConclusionsPoor nutritional status measured by the CONUT-score is independently associated with a poorer postoperative course after RC and is predictive of worse RFS, OS, and CSS. This simple index could serve as a comprehensive personalized risk-stratification tool identifying patients who may benefit from an intensified regimen of supportive cares.     

Prognostic nutritional index and prognosis in renal cell carcinoma: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC).Materials and methodsEligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs).ResultsIn total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I² = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I² = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle–Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757).ConclusionThis meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC.     

Increased preoperative levels of plasma fibrinogen and d dimer in patients with renal cell carcinoma is associated with poor survival and adverse tumor characteristics

Background and objectiveThe relationship between renal cell carcinoma (RCC) and coagulation/fibrinolysis system has been described in several studies. The aim of this study was to investigate the role of 4 different coagulation/fibrinolysis factors on the prediction of histopathologic and survival prognosis in patients with RCC.Patients and methodsData from 128 patients who underwent surgical intervention between March 2006 and January 2011 for RCC were evaluated in this prospective study. Blood samples were collected from all patients on the morning of the operation to measure the plasma fibrinogen, d-dimer, coagulation factor VII, and antithrombin 3 levels. The relationships of these factors in the demographic, clinical, and histopathologic outcomes were analyzed using the Student t, Mann-Whitney U, Kruskal-Wallis, and one-way analysis of variance tests. Receiver operating curve analyses were performed to determine the optimal cutoff level for fibrinogen and d dimer, both of which had a strong relation with the clinical and histopathologic parameters. Disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method. Multivariate Cox regression analyses (forward stepwise logistic regression) were performed to examine the independent prognostic values on survival outcomes.ResultsIncreased plasma fibrinogen and d-dimer levels were associated with tumor size (P = 0.004 and 0.106), nuclear grade (P<0.001 and<0.001), TNM category (P<0.001 and 0.029), and metastasis (P<0.001 and 0.032). Both increased plasma fibrinogen and d-dimer levels predicted decreased DFS (P = 0.027 and 0.04), CSS (P = 0.007 and 0.043), and OS (P = 0.014 and 0.001) rates based on Kaplan-Meier analyses. Furthermore, multivariate analyses demonstrated that fibrinogen independently predicted poor DFS (hazard ratio [HR] = 2.52; 95% CI: 1.04–6.31; P = 0.029) and CSS (HR = 3.89; 95% CI: 1.13–13.40; P = 0.032), whereas d dimer had negative independent prognostic value on OS (HR = 4.01; 95% CI: 1.54–10.50; P = 0.005).ConclusionsIncreased plasma fibrinogen levels accurately predict poor histopathologic and survival outcomes and may be an effective independent prognostic factor in patients with RCC. Moreover, d dimer may serve as a copredictive factor in conjunction with fibrinogen.     

Prostate-specific antigen kinetic profiles during androgen deprivation therapy as prognostic factors in castration-resistant prostate cancer

ObjectiveTo identify pretreatment prognostic factors for patients with castration-resistant prostate cancer (CRPC) undergoing docetaxel (DCT) chemotherapy.Materials and methodsWe retrospectively analyzed 102 patients with CRPC who underwent DCT chemotherapy (dosage: 60–75 mg/m²) from December 2001 to August 2013. The parameters evaluated as prognostic factors were as follows: age, body mass index, Gleason score, clinical TNM stage, prior radical prostatectomy, prior radiation therapy, performance status, presence of pain, laboratory results at the start of DCT, and prostate-specific antigen (PSA) kinetics during prior androgen deprivation therapy (ADT), including PSA level at the start of ADT (PSA-ADT), PSA half-time (PSAT_1/2), time to nadir, PSA level at nadir (PSA-Nadir), duration of nadir, PSA doubling time (PSADT), and PSA level at the start of DCT (PSA-DCT). Univariate and multivariate analyses were performed to identify independent prognostic factors.ResultsMedian cancer-specific survival (CSS) duration following CRPC diagnosis was 28.0 months. In univariate analyses, performance status, serum albumin, serum creatinine, PSAT_1/2, time to nadir, PSA-Nadir, duration of nadir, PSADT, and PSA-DCT showed a potential association with prognosis (P<0.001–0.077). Multivariate analyses of these parameters showed that performance status (hazard ratio [HR] = 0.046; P = 0.046), serum creatinine (HR = 3.028; P = 0.036), PSAT_1/2 (HR = 0.172; P = 0.007), PSA-Nadir (HR = 4.884; P = 0.033), PSADT (HR = 0.148; P<0.001), and PSA-DCT (HR = 5.222; P = 0.004) remained independent predictors of CSS in CRPC.ConclusionsPSA kinetic parameters measured during prior ADT are significant surrogate markers predicting CSS in patients undergoing DCT chemotherapy for CRPC.     

Impact of preoperative serum albumin-globulin ratio on disease outcome after radical cystectomy for urothelial carcinoma of the bladder

IntroductionThe Albumin-Globulin Ratio (AGR; albumin/total protein ? albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB.Material and MethodsWe conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA).ResultsOverall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1–1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1–1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07–1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy.ConclusionpAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation.     

Prognostic value of preoperative albumin-to-fibrinogen ratio (AFR) in patients with bladder cancer treated with radical cystectomy

Introduction and objectivesTo evaluate the prognostic role of albumin-to-fibrinogen ratio (AFR) for the prediction of oncological outcomes in a multi-institutional cohort of bladder cancer (BC) patients treated with radical cystectomy (RC).Materials and methodsWe retrospectively analyzed a multicenter cohort of patients treated with upfront RC for localized (cT1-4aN0M0) BC. Multivariable logistic regression analyses were performed to evaluate the ability of AFR to predict non-organ confined (NOC) disease and lymph-node involvement (LNI) at time of RC. Multivariable Cox’ regression models were performed to evaluate the prognostic effect of AFR on Time-to-Progression (TTP), overall survival (OS), and cancer-specific survival (CSS).ResultsA cut-off value to discriminate between low and high AFR was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.73 with an optimal cut-off at 9.53. Data were available for 246 patients (91 with low AFR, 155 with high AFR). Low AFR was associated with characteristics of tumor aggressiveness and independently predicted NOC (OR 2.11, P = 0.02) and LNI (OR 1.58, P = 0.04) at final pathological report. On multivariable Cox’ regression analyses, preoperative low AFR was independently associated with worse TTP (HR 2.21, P = 0.02), OS (HR 2.24, P = 0.03), and CSS (HR 2.70, P = 0.01).ConclusionPreoperative low AFR is a prognostic biomarker for worse TTP, OS, CSS, and is independently associated with adverse tumor pathological features in BC patients undergoing RC. Our results suggest that especially patients with low AFR may be considered for neoadjuvant treatment.     

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage

ObjectivesTo evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU).Materials and methodsA retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis.ResultsLVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55–2.09], 1.05 [0.62–1.79], 1.15 [0.69–1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44–11.84], 3.17 [1.16–8.67], 2.66 [1.04–6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease.ConclusionIn conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.     

Lymph node count at radical cystectomy does not influence long-term survival if surgeons adhere to a standardized template

IntroductionMultiple bladder cancer studies report that the number of removed lymph nodes (lymph node count [LNC]) at radical cystectomy (RC) is positively associated with survival. Although these reports suggest that LNC can be used as a proxy for surgical quality, all studies used variable or inconsistent pelvic lymph node dissection (PLND) templates. We therefore wished to establish whether LNC at RC influences survival if surgeons adhere to a standardized PLND template.Materials and methodsWe included 274 patients who underwent RC from January 2005 until December 2012. All RCs were performed in either one of 2 hospitals (hospital A or B) by the same 4 urologists (all from hospital A) and a standardized PLND template was applied. PLND specimens were processed by 2 independent pathology departments (hospital A and B). We used Cox regression analysis to investigate the prognostic value of LNC adjusted for patient characteristics. We also compared LNC between hospitals and surgeons and investigated the effect of both the variables on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsMedian LNC was 17 (interquartile range = 12). At a median follow-up of 64.3 months, there was no association between LNC and OS (P = 0.328), CSS (P = 0.645), or DFS (P = 0.450). Median LNC was higher in hospital B than in hospital A (20.0 vs. 16.0, P = 0.003). Median LNC varied significantly among surgeons (12–20, P<0.001). Neither the hospital of surgery nor the surgeon performing PLND influenced OS (P = 0.771 and P = 0.982, respectively), CSS (P = 0.310 and P = 0.691, respectively), or DFS (P = 0.256 and P = 0.296, respectively).ConclusionIf surgeons adhere to a standardized template, LNC at RC does not affect long-term survival.     

Prognostic impact of tumor-associated immune cell infiltrates at radical cystectomy for bladder cancer

ObjectivesTo assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).Material and methodsA total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan–Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10–55).ResultsOf the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.ConclusionsIn this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.     

Retrospective study of systemic immune-inflammation index in muscle invasive bladder cancer: initial results of single centre

Purposes

We aimed to evaluate the prognostic value of the preoperative systemic immune-inflammation index (SII) in patients who underwent radical cystectomy due to muscle invasive bladder cancer (MIBC).

Methods

We researched our cystectomy database between April 2006 and December 2018. Demographic data, operation and postoperative data were recorded. There were 191 MIBC patients who underwent radical cystectomy. After detailed analyses, preoperative SII was calculated by the formula as “(neutrophil)?×?(platelet)/(lymphocyte)”. Cancer-specific survival (CSS) and overall survival (OS) were examined. The prognostic value of SII was analysed with univariate and multivariate Cox proportional hazards regression models. Receiver operating characteristic (ROC) was used to determine the optimum SII. Significant P was P?<?0.05.

Results

The mean follow-up was 37?±?6.7 months. The mean age of patients was 62.1?±?9 years. The optimal cutoff value of SII was determined as 843 in ROC curve (area under the curve: 0.9; P?<?0.001). The CSS and OS were significantly poor in patients with higher SII level (respectively; P?<?0.001, P?=?0.04). Gender, lymph node involvement, pathologic stage, grade and SII were statistically significant in multivariate Cox proportional hazards regression model for CSS.

Conclusions

Preoperative elevated SII could be an independent prognostic factor in MIBC patients who underwent radical cystectomy. If SII?>?843, CSS might be poor. Our results should be confirmed with randomised-controlled prospectively designed future studies with large cohorts.

     

Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

PurposeIdentifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.Material and methodsmRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut‐off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut‐off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis.ResultsAmong 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16–58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01–1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02–1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05–1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR.ConclusionDespite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.     

Neoadjuvant and Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A 2020 Systematic Review and Meta-analysis,and Future Perspectives on Systemic Therapy

ContextTo improve the prognosis of upper tract urothelial carcinoma (UTUC), clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) before or after radical nephroureterectomy (RNU). Despite some new data, the evidence remains mixed on their efficacy.ObjectiveTo update the current evidence on the role of NAC and AC for UTUC.Evidence acquisitionWe searched for all studies investigating NAC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings up to February 2020. A systematic review and meta-analysis was performed.Evidence synthesisFor NAC, the pooled pathologic complete response rate (≤ypT0N0M0) was 11% (n = 811) and pathologic partial response rate (≤ypT1N0M0) was 43% (n = 869), both across 14 studies. Across six studies, the pooled hazard ratios (HRs) were 0.44 (95% confidence interval [CI]: 0.32–0.59, p < 0.001) for overall survival (OS) and 0.38 (95% CI: 0.24–0.61, p < 0.001) for cancer-specific survival (CSS) in favor of NAC. The evidence for NAC is at best level 2. As for AC, there was a benefit in OS (pooled HR 0.77; 95% CI: 0.64–0.92, p = 0.004 across 14 studies and 7983 patients), CSS (pooled HR 0.79; 95% CI: 0.69–0.91, p = 0.001 across 18 studies and 5659 patients), and disease-free survival (DFS; pooled HR 0.52; 95% CI: 0.38–0.70 across four studies and 602 patients). While most studies were retrospective (level 2 evidence), there were two prospective randomized trials providing level 1 evidence. There are currently four phase 2 trials on neoadjuvant immunotherapy and three phase 2 trials on adjuvant immunotherapy for UTUC.ConclusionsNAC for UTUC confers a favorable pathologic response and tumor downstaging rate, and an OS and CSS benefit compared with RNU alone. AC confers an OS, CSS, and DFS benefit compared with RNU alone. Currently, the evidence for AC appears stronger (with positive level 1 evidence) than that for NAC (at best level 2 evidence). Limited data are available for chemoimmunotherapy approaches, but preliminary data support an active research investment.Patient summaryAfter a comprehensive search of the latest studies examining the role of neoadjuvant and adjuvant chemotherapy for upper tract urothelial cancer, the pooled evidence shows that perioperative chemotherapy was beneficial for prolonging survival; however, the evidence for adjuvant chemotherapy was stronger than that for neoadjuvant chemotherapy.     

Caveolin-1 as prognostic factor of disease recurrence and survival in patients treated with radical cystectomy for bladder cancer

Purpose

Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa.

Significance of preoperative butyrylcholinesterase as an independent predictor of survival in patients with muscle-invasive bladder cancer treated with radical cystectomy

ObjectivesButyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC).Methods and materialsWe retrospectively evaluated 327 patients with MIBC who underwent RC from 1996 to 2013 at a single institution. Serum BChE level was routinely measured before operation in all patients. Covariates included age, gender, preoperative laboratory data (anemia, BChE, lactate dehydrogenase, and C-reactive protein), clinical T (cT) and N stage (cN), tumor grade, and RC with/without neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model.ResultsThe median BChE level was 187 U/l (normal range: 168–470 U/l). The median age of the enrolled patients was 69 years, and the median follow-up period was 51 months. The 5-year OS and DFS rates were 69.6% and 69.3%, respectively. The 5-year OS rates were 90.1% and 51.3% in the BChE≥168 and<168 U/l groups, respectively (P<0.001). The 5-year DFS rates were 83.5% and 55.4% in the BChE≥168 and≤167 U/l groups, respectively (P<0.001). In the univariate analysis, BChE, cT, cN, and RC with/without neoadjuvant chemotherapy were significantly associated with both OS and DFS. Multivariate analysis revealed that BChE was the factor most significantly associated with OS, and BChE, cT, and cN were significantly associated with DFS.ConclusionsThis study validated preoperative serum BChE levels as an independent prognostic factor for MIBC after RC.     

High expression of ERBB2 is an independent risk factor for reduced recurrence-free survival in patients with stage T1 non-muscle-invasive bladder cancer

IntroductionMolecular markers associated with breast cancer are assumed to be associated with outcome in non-muscle-invasive bladder cancer (NMIBC).Materials and methodsWe retrospectively investigated the association of the mRNA expression of estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR), MKI67, and HER2 (ERBB2) with recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) in 80 patients with stage T1 NMIBC.ResultsHigh expression of ESR2 (P = 0.003), ERBB2 (P < 0.001), and MKI67 (P = 0.029) was associated with shorter RFS. Only high ERBB2 was an independent prognostic factor for reduced RFS (HR = 2.98; P = 0.009). When sub stratifying the cohort, high ESR2 was associated with reduced RFS (P < 0.001), CSS (P = 0.037) and OS (P = 0.006) in patients without instillation therapy. High ESR2 was associated with reduced CSS (P = 0.018) and OS (P = 0.029) in females and with shorter RFS in both sexes (males: P = 0.035; females: P = 0.010). Patients with high ERBB2 showed reduced CSS (P = 0.011) and OS (P = 0.042) in females and reduced CSS (P = 0.012) in those without instillation, while RFS was significantly reduced irrespective of sex or instillation.ConclusionHigh mRNA expression of ERBB2 is an independent predictor of reduced RFS in patients with stage T1 NMIBC. High ERBB2 and ESR2 are associated with reduced outcomes, especially in females and patients without instillation therapy.     

Sarcopenia as a predictor of postoperative outcomes after urologic oncology surgery: A systematic review and meta-analysis

AimSarcopenia as a reliable prognostic predictor in urologic oncology surgery remains controversial, and no consensus amongst researchers exists regarding the management of patients with sarcopenia. This meta-analysis was conducted to investigate the association between sarcopenia and postoperative outcomes after urologic oncology surgery.MethodsA systematic search in MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library databases was conducted to identify the potential studies published before August 2019. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance with random or fixed effects models.ResultsSeventeen retrospective cohorts comprising 3,948 patients were included with sarcopenia prevalence between 25% and 68.9%. Patients with sarcopenia had significantly shorter overall survival (OS; HR = 2.06, 95% CI: 1.44–2.95; P < 0.001; I-square (I²) = 86%) and cancer-specific survival (HR = 2.16, 95% CI: 1.60–2.92; P < 0.001; I² = 49.4%) than those without sarcopenia. Sarcopenia was independently associated with increased all-cause mortality (HR = 1.50, 95% CI: 1.26–1.80; P < 0.001; I² = 0%) and cancer-specific mortality (HR = 1.50, 95% CI: 1.12–2.01; P = 0.006; I² = 0%). No prognostic difference was observed in the postoperative risk of total complications and systemic progression except lymphovascular invasion status.ConclusionsSarcopenia is an independent poor prognostic factor for patients undergoing urologic oncology surgery, particularly postoperative risks of short survival and increased mortality. Thus, preoperative sarcopenia evaluation can provide clinicians with important information to guide and individualise patient management and improve surgical outcomes.     

Age ≥ 80 years is independently associated with survival outcomes after radical cystectomy: Results from the Canadian Bladder Cancer Network Database

ObjectivesThe role of advanced age as an independent prognostic factor for clinical outcomes after radical cystectomy is controversial. The objective of the current study was to assess the associations between age and clinical outcomes in a large, multi-institutional series of patients treated with radical cystectomy for bladder cancer.Materials and methodsInstitutional radical cystectomy databases containing detailed information on bladder cancer patients treated between 1993 and 2008 were obtained from 8 academic centers in Canada. Data were collected on 2,287 patients and combined into a relational database formatted with patient characteristics, pathologic characteristics, recurrence status, and survival status. Patient age was coded as <60 years, 60–69 years, 70–79 years, or ≥80 years. Clinical outcomes were 30-day mortality, 90-day mortality, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). Logistic regression and Cox proportional hazards regression analysis were used to analyze survival data.ResultsFive hundred fifty-seven (24.6%), 679 (30.0%), 846 (37.4%), and 181 (8.0%) patients were <60 years, 60–69 years, 70–79 years, and ≥80 years, respectively. Increased age was associated with decreased utilization rates of neoadjuvant chemotherapy (P = 0.0143), adjuvant chemotherapy (P < 0.0001), and continent urinary diversion (P < 0.0001) as well as advanced pathologic tumor stage (P = 0.0003), increased positive surgical margins (P < 0.0001), and lymphovascular invasion (P = 0.0335). Compared with patients < 60 years, multivariate regression analysis showed that age ≥ 80 years was independently associated with 90-day mortality (OR 2.98, 95% CI 1.22–7.30), OS (HR 2.03, 95% CI 1.51–2.75), DSS (HR 1.56, 95% CI 1.09–2.24), and RFS (HR 2.06, 95% CI 1.57–2.70).ConclusionsAge ≥ 80 years at the time of radical cystectomy was independently associated with adverse survival outcomes. These data suggest that increased chronologic age should be considered in clinical trial design and in nomograms predicting survival.     

Unmarried men have worse oncologic outcomes after radical cystectomy for nonmetastatic urothelial bladder cancer

BackgroundUnmarried status is an established risk factor for worse cancer control outcomes and survival in various malignancies. We tested the effect of marital status on the rate of nonorgan confined disease as well as on cancer-specific mortality (CSM) in patients who underwent radical cystectomy for nonmetastatic urothelial bladder cancer (UCUB).MethodsWithin the Surveillance, Epidemiology and End Results database (2007-2015), we identified 11,167 patients (8,639 men and 2,528 women) who underwent radical cystectomy for nonmetastatic UCUB. Temporal trend analyses, logistic regression models, cumulative incidence plots, competing-risks regression models and landmark analyses were used.ResultsOverall, 2,454 men (28.4%) and 1,363 women (53.9%) were unmarried. Unmarried men had a higher rate of nonorgan-confined disease at radical cystectomy (OR: 1.24, CI 1.10–1.33; P < 0.001). Moreover, in men, unmarried status was an independent predictor of higher CSM (HR: 1.24, CI 1.12–1.37) In women, unmarried status neither predicted nonorgan-confined disease at radical cystectomy (OR: 1.07, CI 0.91–1.26; P = 0.37) nor was it associated with CSM (HR: 1.13, CI 0.88–1.31; P = 0.14). In 6-month landmark analyses, unmarried status remained an independent predictor of higher CSM in men (HR: 1.20, CI 1.08–1.33).ConclusionsUnmarried men have more advanced tumor stage at radical cystectomy and worse CSM compared to married men. Interestingly, marital status did not affect oncologic outcomes in women. These data suggest a gender-specific effect of marital status in UCUB.     

Association of intraoperative hypothermia with oncologic outcomes following radical cystectomy

IntroductionIntraoperative hypothermia (IOH) has been suggested to adversely impact outcomes following surgery. The objective of this study was to evaluate the association between IOH and survival following radical cystectomy (RC).MethodsPatients who underwent RC for bladder cancer from 2003 to 2018 were identified in our cystectomy registry. Intraoperative temperatures were extracted from the anesthesia record. IOH was defined as a median intraoperative temperature <36°C, and severe IOH as ≤ 35°C. Time under 36°C was assessed as a continuous variable. Recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between IOH and outcomes were assessed with multivariable Cox proportional hazards models.ResultsA total of 852 patients were identified, among whom 274 (32%) had IOH. Median follow up among survivors was 4.9 years (IQR 2.4–8.7), during which time 483 patients died, including 343 from bladder cancer. Two-year survival was not significantly different between patients with and without IOH (CSS: 74% vs. 71%, P= 0.31; OS: 68% vs. 67%, P= 0.13). Following multivariable adjustment, neither IOH nor time under 36°C was significantly associated with survival. A total of 37 patients (4.3%) had severe IOH. These patients were observed to have significantly lower 2-year OS (56% vs. 68%, P= 0.005); however, this association did not remain statistically significant after multivariable adjustment (P= 0.92).ConclusionIOH was not independently associated with survival following RC. These data do not support IOH as a prognostic factor for cancer outcomes among patients undergoing RC.