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Purpose: To improve patient selection for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in bladder cancer patients (BCa)., Methods: Retrospective evaluation of 1057 patients with cT2-4N0M0 BCa treated with RC and pelvic lymph node dissection between 1990 and 2018 at 3 referral centers. Adverse pathologic features (APF) were defined as pT3-pT4/pN + disease at RC. A regression tree model (CART) was used to assess preoperative risk group classes. A multivariable logistic regression (MVA) was performed to identify predictors of APF at RC., Results: Median age was 70 years and most of the patients were men (83%). Of the 1057 patients included in our study, 688 (65%) had APF. CART analysis was able to stratify patients into 3 risk groups: low (cT2 and single disease, odds ratio [OR] 0.62), intermediate (cT2 and multiple disease, OR 1.08), and high (cT3-cT4, OR 1.28). On MVA APF were associated with variant histology (odds ratio [OR] 3.97, 95% confidence interval [CI] 1.46-10.83, p = 0.007), multifocality at TUR (OR 2.56, CI 1.27-5.17, p = 0.09), completeness of resection (OR 0.47, CI 0.23-0.96, p = 0.04) and clinical extravesical disease (OR 3.42, CI 1.63-7.14, p = 0.001)., Conclusion: We defined three pre-operative risk classes. Our results indicate that patients with a cT3-T4 disease are those who might benefit more from NAC whereas those with T2 single disease should be those to whom NAC probably shouldn't be proposed. Given the high rate of understaging in BCa patients, NAC can be proposed in selected cases of cT2/multifocal disease.

Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy., Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b + tumor-associated-neutrophils (TAN) and CD3 + T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed., Results: Basal type BC contained a significantly higher density of CD66b + TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model., Conclusions: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance., Competing Interests: The authors declare no competing financial interests.

Purpose: To evaluate the role of a complete transurethral resection of bladder tumors (c-TURBT) on oncological outcomes after radical cystectomy (RC) and its relationship with adverse pathological features., Methods: We retrospectively analyzed data of 727 patients treated with RC and bilateral pelvic lymph node dissection at three tertiary referral centers. Possible c-TURBT was reported by the treating surgeon. Multivariable Cox regression analyses were used to assess the relationship of c-TURBT and survival outcomes after surgery in 1:1 propensity score-matched cohort adjusted for age and gender. Moreover, multivariable logistic regression (MVA) was built to predict the relationship between c-TURBT and pT3-T4 stages at RC, lymph node invasion (LNI) and positive soft tissue surgical margin (STSM)., Results: A total of 433 (60%) patients received a c-TURBT. 3.0% of patients with a c-TURBT achieved a pT0-pTa-pTis status vs. 2.0% of patients with incomplete TURBT. At multivariable Cox regression analyses, c-TURBT was not associated with survival outcomes. At MVA, incompleteness of TURBT was significantly associated with a pT3-T4 stage [odds ratio (OR) 8.04, 95% confidence interval (CI) 2.33-27.67, p = 0.001]. No significant association was found between c-TURBT, LNI and STSM., Conclusion: We found a low rate of achievement of pT0 stage at RC. An incomplete TURBT before RC represented a predictor of pT3-T4 stages, but no effect of a c-TURBT was shown on survival outcomes. Given the current inadequacy of clinical staging strategies with more than 50% of extravesical disease being under-staged, our results could improve patients selection for NAC, driving the decision-making in doubtful cases.

Background: According to International Guidelines radical cystectomy (RC) should not be delayed over 90 days to prevent the risk of intercurrent progression and worse survival. Nevertheless, such a recommendation relies on a few retrospective studies reaching non-univocal conclusions. Aim of the present study was to investigate if the latency between diagnosis and cystectomy (LDC) is related to prognosis after RC., Methods: Retrospective analysis of database collecting complete information on patients undergone RC at single institution since 2004. The cases with an LDC <15 or >360 days or submitted to neo-adjuvant chemotherapy or with distant metastasis were excluded. Uni- and multivariate analyses assessed the relationship between LDC upstaging, progression-free and overall survival., Results: The data of 376 patients were analyzed; mean/median LDC was 83/76 days and 124 patients (33%) had LDC>90 days. LDC was shorter in younger patients with first diagnosis of more advanced BC at clinical staging; accordingly, patients with LDC<90 days had more advanced disease also at final pathology. Prevalence of pathological upstaging was 37%; in case of upstaging LDC was 75 days vs. 72 days (P=0.4629). Multivariable regression models adjusted for pathological local and lymph nodal stage showed that LDC, continuous or dichotomized at 30/60/90/120/180/240 days was not related to progression-free or overall survival. The retrospective design of study is the main limitation of the study., Conclusions: In our experience nor the risk of upstaging, neither survival after RC were related to LDC. Even if these results should not discourage any effort to perform surgery expeditiously, the window of opportunity for RC might not be delimited by a predetermined threshold.

Background: The objective of this study was to evaluate if use of an ileal conduit (IC) versus a neobladder (NB) during radical cystectomy (RC) can play a role in the morbidity of the surgical procedure., Patients and Methods: Since 2001 our institution has prospectively maintained a database of more than 500 patients who have undergone RC. The records of 258 patients who received an RC and IC and 121 who received an RC and NB were reviewed for the present study. Using a binary logistic regression model a propensity score was generated for the following factors: sex, age, smoking habit, Charlson score, American Society of Anesthesiology score, preoperative hydronephrosis, and pathologic T stage. Two groups of patients with similar propensity scores were created with a ratio of 1:1, one group who received an IC and another who received an NB. The following features were compared between the 2 groups: blood loss, intraoperative complication rate, time to oral intake resumption, postoperative complication rate (overall, Clavien classification 1-2, Clavien classification 3-5, related to RC, related to urinary reconstruction)., Results: In total, 170 patients were selected; 85 with NB, 85 with IC, and the 2 groups were well matched according to the desired features. No differences were noted for all of the compared features., Conclusion: The morbidity of RC does not seem to be affected by the choice of IC versus NB., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to evaluate whether performing an ileal conduit (IC) versus a neobladder(NB) during radical cystectomy (RC) can play a role on the morbidity of the surgical procedure., Materials and Methods: At our institution since 2001, a database collecting the data of more than 450 patients who have undergone RC is perspectively maintained.The records of 246 patients submitted to RC and IC and 120 to RC and NB have been reviewed for the present study. By a binary logistic regression model, a propensity score was generated joining these factors: gender,age, smoking habit, Charlson’ comorbidity score, platelet antiaggregants or oral anticoagulant therapy, ASA(American Society of Anesthesiologists) score, hydronephrosis, pathologic T stage, and lymphadenectomy. A group of patients submitted to IC and another to NB having the closer propensity score were created with a matching ratio of 1:1. The following features were compared between the two groups: operative time, blood loss,intraoperative complication rate, and postoperative complications rate (overall, clavien 1-2, clavien ≥, related toRC, relate to urinary reconstruction).Results: One hundred thirty-four patients were selected, 67 submitted to NB, 67 to IC, well matched according to the desired features. No differences were noted for all the compared features.Conclusion: The morbidity of RC does not seem to be dependent on the choice to perform IC versus NB.