Concomitant Carcinoma In Situ Research Articles

Diagnostic performance and predictive capacity of early urine cytology after transurethral resection of nonmuscle invasive bladder cancer: A prospective study

ObjectivesTo prospectively evaluate the value of early urine cytology (EUC) after the primary transurethral resection of bladder tumor (TURBT) of nonmuscle invasive bladder cancer (NMIBC) for the prediction of positive biopsy findings on repeat TURBT. MethodsAfter approval of institutional review board, patients who underwent TURBT for NMIBC between February 2014 and July 2018 were included in the study. Patients with concomitant Carcinoma in Situ (CIS), upper tract urothelial tumors, biopsy proven muscle invasion, or low-risk NMIBC (single, primary, Ta, and G1 tumor) were excluded. Forty-eight hours after primary TURBT, EUC was retrieved and patients were scheduled for repeat TURBT 2 to 6 weeks later according to the predetermined protocol. The primary outcome was to determine the role of positive EUC to predict positive biopsy findings on repeat TURBT. ResultsDuring the study period, 198 patients fulfilled the study inclusion criteria of which 49 (25%) had recurrent NMIBC. Primary TURBT pathology results showed T1 stage in 195 (98.5%) patients and high-grade malignancy in 158 (79.8%). Intermediate- and high-risk NMIBC were defined in 49 (25%) and 149 (75%) patients, respectively. EUC was positive in 114 patients; of whom 78 (68.4%) showed positive biopsy findings on repeat TURBT (P = 0.001). The sensitivity, specificity, negative, and positive predictive values of EUC for biopsy findings at repeat TURBT were 90% (95%CI: 87–94), 75% (95%CI: 71–79), 89% (95%CI: 85–94), and 68% (95%CI: 62–74), respectively. On mean (±SD) follow-up of 42(±13) months, tumor recurrence was encountered in 101 (53%) patients. On multivariate Cox regression analysis, EUC was significantly associated with tumor recurrence (HR = 4.6, 95%CI: 2.37–8.9, P < 0.001). ConclusionsPositive EUC after primary TURBT for NMIBC is significantly associated with positive repeat TURBT for malignancy. EUC is an independent predictor of tumor recurrence. EUC might be implemented after primary TURBT to help refining indications of repeat biopsy and planning of further intervention.

Canadian experience of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy for muscle-invasive bladder cancer.

Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Neoadjuvant chemotherapy (NAC) was proven to cause pathological downstaging. For this reason, we evaluated whether receipt of NAC decreases local bladder recurrences in TMT patients. We retrospectively analyzed our TMT database for all patients treated between 2003 and 2017. Patients were treated with maximal transurethral resection of bladder tumor (TURBT) followed by chemotherapy/radiotherapy with or without NAC. Baseline demographic and tumor characteristics were recorded. Rates of local and systemic recurrence were analyzed per receipt of NAC. Overall recurrence-free survival (RFS) and bladder (b)RFS were analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. Median age and followup periods were 72 years and 3.6 years, respectively. Fifty-four patients had NAC and concurrent chemoradiation (NAC-TMT) vs. 70 patients who had concurrent chemoradiation only (TMT). Carcinoma in situ (CIS) was present in 31% of the patients in NAC-TMT group compared to 24% in TMT group (p=0.40). After treatment, 24 (44%) and 31 (44%) patients in NAC-TMT and TMT groups, respectively, had bladder tumor recurrence. Overall RFS at three years was 46% and 50% in NAC-TMT and TMT groups, respectively (p=0.70). BRFS at three years was 55% and 69% in NAC-TMT and TMT groups, respectively (p=0.27). Multivariable analyses found that the presence of concomitant CIS (hazard ratio [HR] 2.13; 95% confidence interval CI 1.06-4.27; p=0.0036) was the primary factor associated with local bladder recurrence. Receipt of NAC does not obviate the risk of bladder recurrence post-TMT. Patients with CIS should be monitored especially closely for local recurrence.

PD60-10 IMPACT OF PREOPERATIVE CONTROLLING NUTRITIONAL STATUS (CONUT) SCORE ON PERIOPERATIVE MORBIDITY AND SURVIVAL OUTCOMES IN PATIENTS WITH BLADDER CANCER TREATED WITH RADICAL CYSTECTOMY: A MULTICENTER ANALYSIS

INTRODUCTION AND OBJECTIVE:Despite several improvements in surgical technique, radical cystectomy (RC) remains an highly morbid operation and even in contemporary series the combined surgical, medi...

MP55-07 PREDICTIVE AND PROGNOSTIC ROLE OF A SIMPLE IMMUNO-PHENOTYPICAL SCORE IN CLINICAL MANAGEMENT OF PATIENTS WITH PT2 INVASIVE UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVE: The mapping of the genome through the TCGA collaborative project recently revealed major intrinsic molecular subtypes, Basal, Luminal, and Neural muscle-invasive urothelial carcinoma (UC), which have shown prognostic and predictive values. A standardized approach in daily practice, which is simple, fast, reproducible, and at low cost has not yet been identified. We provide to test the hypothesis that immuno-phenotypical score classification (Piescore) may discriminate Luminal from Basal from Neural UC, and to find an association of tumor Piescore with histological and clinical prognostic variables in a mono-institutional cohort of muscle-invasive (pT2) UC treated with trans-urethral resection and radical cystectomy (RC). METHODS: Primary endpoint is to stratify Luminal, Basal or Neural tumors according to a simple immuno-phenotypical score. Consecutive transurethral resection specimens harbored foci of high grade, pT2 (MIBC) from 75 pts who subsequently underwent RC, have been submitted for immunohistochemical analysis, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore divided the tumors into Basal and Luminal types when at least 3 of 4 markers were consistent with a specific phenotype. RESULTS: Luminal and Basal phenotype was present in 32 pts and 29 pts (43% and 39% respectively) while in 7 pts (9% of cases) the Piescore indentified a mixed phenotype (when 2 Luminal markers and 2 Basal markers were present simultaneously). No expression was identified in 7 pts (9%): 4 cases (5%) with morphological neuroendocrine differentiation and 3 cases (4%) with classical urothelial differentiation, all consistent with Neural phenotype. Basal Piescore with all markers consistent with basal differentiation (CD44+, CK5/6+, CK20-, pPARg-) was associated with advance stage at cystectomy (pT3-4 vs pT0-1-2, 73% vs 27% of cases respectively). Only necrosis, among histopathological parameters considered, was statistically correlated with Basal phenotype (OR: 3.3, p: 0.030), while no association with lymph-vascular invasion, papillary subtype, primary tumor, and concomitant CIS was found. CONCLUSIONS: Piescore immunophenotyping could be a simple surrogate in alternative to genome profiling, able to stratify UC-TURB patients between Luminal vs Basal type. The basal phenotype identified with immunohistochemical markers CD44, CK5/6, CK20 and pPARg seems to stratify more aggressive UC at cystectomy. Neural Piescore also identified a subset of high-grade carcinomas that harbored classical features of UC at histology. Indeed, the biological significance of the expression of multiple phenotypes in the same UC (Piescore mixed tumors) has to be further evaluate. Further studies are mandatory in order to confirm and extend our finding to clinical utility. Source of Funding: None.

Optimum Management Of The T1 High Grade Bladder Cancer

Objectives: To determine the optimum treatment option for patients with superficial high grade (T1Hg) bladder cancer. Introduction: Controversy exists about the most appropriate treatment for superficial high grade (T1Hg) bladder cancer. Immediate cystectomy offers the best chance for survival but associated with an impaired quality of life compared with conservative therapy. In case of conservative therapy lifelong surveillance is required and there is a high rate of recurrence and risk of disease progression. So optimum treatment option should be determined to treat the disease optimistically. Methods: A comprehensive and systemic search of the pubmed database for English Language articles was performed using the following medical subject Heading (MeSH): Bladder cancer, treatment of superficial high grade (T1Hg) bladder cancer, treatment options for bladder cancer, natural history of T1Hg bladder cancer, newer Intravesical agents, cystectomy and in addition reference of relevant articles were searched for additional references. Results: Approximately 70% of all newly diagnosed bladder tumors are non-muscle invasive bladder cancer. The management of these patients entails transurethral resection with or without adjuvant intravesical therapy. After review of obtained articles it is evident that the conservative treatment of T1Hg bladder cancer should be ended when there is systemic or local toxicity from intravesical therapy or patient is not complaint or persistence of tumor or tumor progression despite therapy. Conclusion : The management of T1Hg is highly variable due to several factors including divergence in treatment related evidence. The efficacy of treatments must be balanced with their toxicity, so that single treatment option cannot be considered superior across all Non-Muscle Invasive Bladder Cancer (NMIBC). Immediate radical cystectomy may be offered upfront in patients with T1Hg tumors with concomitant CIS or multiple recurrent high grade tumors. Bangladesh Journal of Urology, Vol. 16, No. 1, Jan 2013 p.26-32

Impact of time to second transurethral resection on oncological outcomes of patients with high-grade T1 bladder cancer treated with intravesical Bacillus Calmette-Guerin.

To determine the impact of time to restaging transurethral resection (Re-TUR) on recurrence-free survival (RFS), progression-free survival (PFS), and cancer specific survival (CSS) of patients with high-grade T1 bladder cancer (BC) treated with intravesical Bacillus Calmette-Guerin (BCG). Our prospectively maintained NMIBC databases were queried to identify patients with high-grade T1 BC who underwent Re-TUR before receiving intravesical BCG treatment (induction + 1-year maintenance). Patients were divided into three groups based on time to Re-TUR (group A: ≤ 6weeks; group B: > 6-12weeks; group C: > 12-18weeks). Kaplan-Meier plots were used to estimate differences in RFS, PFS, and CSS. Multivariate Cox regression analysis was used to assess the impact of time to Re-TUR on oncological outcomes. Overall, 269 high-grade T1 BC patients were eligible for the analysis. Nineteen (7.1%) had concomitant CIS. Median follow-up was 49.3 (IQR 25-65) months. Kaplan-Meier plots showed no differences in RFS, PFS, and CSS between the three groups. Multivariate Cox regression analysis showed that Group B had a slightly better RFS, while the other outcomes were not affected by time to Re-TUR. This is the first study testing the role of time to Re-TUR in a homogeneous population of patients with high-grade T1 BC who received complete BCG treatment. The study challenged the concept the sooner the Re-TUR the better, since time to Re-TUR did not significantly affect oncological outcomes.

Outcomes and complications of Hyperthermic IntraVesical Chemotherapy using mitomycin C or epirubicin for patients with non-muscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure.

IntroductionChemohyperthermia is a feasible option in BCG (bacillus Calmette-Guérin) failure patients who desire bladder preservation. We aimed to assess outcomes and complications of chemohyperthermia using mitomycin C (MMC) or epirubicin (EPI).Material and methodsFrom March 2017 to February 2020, 103 BCG failure or intolerance patients with high-risk NMIBC (non-muscle invasive bladder cancer) underwent a hyperthermic intravesical chemotherapy (HIVEC) regimen. Five patients did not complete at least 5 instillations and were excluded from analysis. MMC was used in 72 out of 98 patients (Group A) while EPI was used in 26 patients (Group B). Response to HIVEC, predictive factors for treatment outcome and the disease-free survival (DFS) were defined as primary endpoints. The complications of chemohyperthermia were assessed as a secondary endpoint.ResultsNo significant differences were found in recurrence and progression after induction course between Groups A and B. Kaplan-Meier disease-free survival was 22.61 months in Group A and 21.93 in Group B. The log-rank test showed no statistically significant difference between the two curves (p = .627). In the multivariate analysis, patients with tumor size ≥3 cm (p = .029), recurrence rate >1/year (p = .034), concomitant carcinoma in situ (CIS) during transurethral resection of bladder (TURB) (p = .039) and BCG-unresponsive status (p = .048) were associated with a worse response to chemohyperthermia. The use of MMC or EPI did not influence the response to treatment (p = .157). A slightly significant higher rate of overall complications (p = .0488) was observed in Group B. A significantly higher rate of Grade 3 frequency/urgency (p = .0064) contributed to this difference. The use of EPI was the only independent factor associated with severe urinary frequency/urgency (p = .017). No patients experienced Grade 4/5 adverse events.ConclusionsHIVEC can be considered a feasible option in BCG failure/intolerant NMIBC patients, avoiding or postponing radical cystectomy in some particular subclasses of patients.

Prognostic Role of mRNA-Expression of Aquaporins (AQP) 3, 4, 7 and 9 in Stage pT1 Non-Muscle-Invasive Bladder Cancer.

AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research. To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making. Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR. Of the 112 patients (83.9%male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6%and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029). mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy.

Role of androgen receptor expression in non-muscle-invasive bladder cancer: a systematic review and meta-analysis.

In order to evaluate the potential prognostic/predictive role of androgen receptor (AR) expression in non-muscle-invasive bladder cancer (NMIBC), and whether it may represent a therapeutic target, we conducted a systematic search of the literature using 'androgen receptor or AR', 'testosterone', 'bladder cancer' and 'non-muscle invasive bladder cancer or NMIBC' as keywords. Eleven studies met the inclusion/exclusion criteria. No significant association was found between AR status and patients' gender (p=0.232), tumor size (p=0.975), tumor stage (p=0.237), tumor grade (p=0.444), tumor multicentricity (p=0.397), concomitant CIS (p=0.316) and progression of disease (p=0.397). On the other hand, relative lack of AR expression was significantly correlated to recurrent disease (p=0.001). Evidence for a direct correlation between AR expression and recurrence-free survival of patients with NMIBC indicate ARs as potential markers of BC behavior; moreover, the finding of a role of androgen blockade therapy in improving survival highlights the potential clinical application of this pathway, which deserves to be further explored.

Loss of CHEK2 Predicts Progression in Stage pT1 Non-Muscle-Invasive Bladder Cancer (NMIBC).

Downregulation of checkpoint protein kinase 2 (CHEK2), which is involved in DNA repair, is associated with poorer outcome in various tumors. Little is known about the role of CHEK2 in urothelial carcinoma of the bladder (UCB). In the present study, we investigated the prognostic impact of CHEK2 protein expression in stage pT1 UCB. This retrospective, single-center analysis was carried out in a cohort of patients initially diagnosed with a pT1 UCB between 2007 and 2015. Immunohistochemical (IHC) staining of CHEK2 was performed. CHEK2 expression was correlated with recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) using Kaplan-Meier analysis and multivariable Cox regression analysis. The analysis included 126 patients (86% male, median age 71years). Loss of immunohistochemical protein expression of CHEK2 (<10%) was associated with significantly worse PFS (p = 0.041). Likewise, CHEK2 loss identified a subgroup of patients with worse PFS in the high-risk groups with concomitant CIS (p = 0.044), multifocal tumors (p < 0.001) and tumor grading G3 according to WHO1973 (p = 0.009). Multivariable Cox regression analysis revealed both loss of CHEK2 expression (HR: 4.18, 95%-CI: 1.35-12.93; p = 0.013) and multifocal tumors (HR: 4.53, 95%-CI:1.29-15.92; p = 0.018) as the only predictive factors for progression. Loss of IHC expression of CHEK2 in pT1 UCB is an independent predictor for progression to muscle-invasive disease and is also associated with worse PFS. This could help to identify high-risk patients who would benefit from early cystectomy.

The concomitant EGFR T790M/C797S in trans and cis in three osimertinib-resistant lung adenocarcinoma patients.

e20105 Background: EGFR C797S mutation is an important cause of Osimertinib resistance. Previous studies showed that patients harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors (TKI). However, patients harboring EGFR C797S in cis with T790M are resistant to combination therapy or each single reagent. Methods: We performed next-generation sequencing on peripheral blood samples from patients with advanced lung adenocarcinoma who had been undergoing targeted therapy. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 14 lung cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: Among 6489 Lung adenocarcinoma patients sample, we identified concomitant trans and cis EGFR T790M/C797S in three patients with very poor prognosis. All three patients were sensitive to the first-generation EGFR TKI, and took Osimertinib when disease progressed. When resistant to Osimertinib, the patients went to genetic testing to find new target therapy. Patient No. 1 was a 66-year-old man with mutations of EGFR exon 19del (25.08%), EGFR T790M (10.08%) / C797S (5.37%) in trans and in cis, TP53 exon8 mutation (12.35%). This patient died 20 days after the genetic testing without any further treatment. Patient No. 2 was a 53-year-old woman who carried gene mutations including EGFR exon 19del (0.51%), EGFR T790M (0.57%) and C797S (0.47%) in trans and in cis. She was treated with the combination of first- and third-generation EGFR TKI, and disease progressed after 50 days. She died half months after the gene test. Patient No. 3 was a 63-year-old woman whose gene mutation included EGFR L858R (77.49%), EGFR T790M (40.94%) and EGFR C797S (5.46%) in trans and in cis, also combined with EGFR amplification. Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor Anlotinib was attempted, but the patient died within one month after the gene test. Conclusions: We firstly reported three cases with concomitant EGFR T790M/C797S in trans and EGFR T790M/C797S in cis mutation in the word. Physicians tried either the EGFR TKI inhibitor combination therapy or VEGFR inhibitor, but neither of them had an effect on these patients. All three patients had very poor prognosis and died within two months of the gene test, indicating that the concomitant of the cis and trans mutation could be a very important prognostic prediction factor.

Prognostic Significance of the Lymphocyte-to-Monocyte Ratio in Bladder Cancer Undergoing Radical Cystectomy: A Meta-Analysis of 5638 Individuals.

Introduction A growing number of studies have explored the association between the pretreatment lymphocyte-to-monocyte ratio (LMR) and survival outcomes in various cancers. However, its prognostic significance on bladder cancer remains inconsistent. The aim of this meta-analysis was to evaluate the prognostic value of pretreatment LMR in bladder cancer. Methods The MEDLINE, EMBASE, Cochrane Library, and CNKI databases were comprehensively searched for relevant studies. A meta-analysis of overall survival (OS), recurrence-free survival (RFS), or cancer-specific survival (CSS) clinicopathological features was conducted. Results Nine studies containing 5,638 cancer patients were analyzed in this meta-analysis. Patients with high LMR tended to have favourable OS (HR: 0.63, 95% CI: 0.50-0.80, P < 0.001), RFS (HR: 0.59, 95% CI: 0.38-0.91, P = 0.017), and CSS (HR: 0.76, 95% CI: 0.70-0.83, P < 0.001). Moreover, low LMR was highly correlated with age (≥60), differentiation (low), T stage (III-IV), lymph node metastasis (yes), and concomitant Cis (yes). Conclusion Pretreatment LMR might be a useful predictor of survival outcomes in patients with bladder cancer.

Concomitant carcinoma in situ may not be a prognostic factor for patients with bladder cancer following radical cystectomy: a PRISMA-compliant systematic review and meta-analysis.

Numerous recent studies have shown that concomitant carcinoma in situ (CIS) can be closely associated with the prognosis of patients with bladder cancer (BCa). However, the prognostic value of CIS in BCa is still not conclusive. Hence, we performed a systematic review and meta-analysis to explore the association between CIS and clinicopathological features and the prognostic value for BCa following radical cystectomy. We performed this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were systematically collected from PubMed, EMBASE, and Web of Science, with an expiration date of August 2018. Hazard ratios and 95% confidence intervals (CIs) were pooled to assess the intensity of association. All data were analyzed by Stata 12.0. Moreover, heterogeneity and publication bias were determined, and sensitivity analysis was performed to examine whether the findings of the meta-analysis were robust. A total of 18,845 patients from 24 studies were included in the analysis. Our results indicated that CIS has no significant correlation with cancer-specific mortality (CSM) (pooled HR = 0.97, 95% CI 0.93-1.00, p = 0.059), overall mortality (OM) (pooled HR = 0.93, 95% CI 0.85-1.01, p = 0.076), overall survival (OS) (pooled HR = 1.04, 95% CI 0.96-1.12, p = 0.386), cancer-specific survival (CSS) (pooled HR = 1.06, 95% CI 0.97-1.16, p = 0.186), recurrence-free survival (RFS) (HR = 1.05, 95% CI 0.99-1.11, p = 0.098) or recurrence (pooled HR = 1.04, 95% CI 0.98-1.11, p = 0.212) in BCa patients. In addition, CIS was not correlated with gender (male vs. female, OR = 1.00, 95% CI 0.74-1.34, p = 0.978), pathological stage (III/IV vs. I/II: OR = 0.74, 95% CI 0.50-1.10, p = 0.132), tumor grade (1/2 vs. 3: OR = 3.38, 95% CI 0.73-15.65, p = 0.119), soft tissue surgical margin (STSM) (+ vs. - : OR = 1.20, 95% CI 0.97-1.48, p = 0.093) or lymphovascular invasion (LVI) (+ vs. - : OR = 0.92, 95% CI 0.62-1.38, p = 0.702),but was closely related to adjuvant chemotherapy (ACT) (yes vs. no, OR = 1.17, 95% CI 1.03-1.32, p = 0.019). Furthermore, these findings were demonstrated to be reliable by our sensitivity and subgroup analysis. The prognostic value of CIS in BCa remains inconclusive in patients submitted to RC. Our data indicated that CIS may have no significant correlation with the prognosis and clinicopathological parameters of BCa patients, and also may not be applied to risk stratification or individualized therapy in BCa patients. Further research should be conducted to confirm our findings.

Long term oncologic outcome in patients with bladder cancer after radical cystectomy: Impact of carcinoma in situ in the era of neoadjuvant chemotherapy.

To assess the impact of carcinoma in situ (CIS) on oncologic outcomes in patients who underwent radical cystectomy, with a focus on those who received neoadjuvant chemotherapy (NAC) including patients with down-staging to ≤ pT1cancer after chemotherapy. All patients who underwent radical cystectomy for urothelial cancer with curative intent from 1985 to 2011 were included. The impact of CIS on recurrence free and overall survival (OS) was assessed in the whole cohort and a subgroup who received NAC as well as those with response to chemotherapy and down-staging to ≤ pT1. A total of 2518 patients with a median follow-up period of 9years were included. Among all, 1397 (55.5%) had concomitant CIS on final pathology. CIS was associated with high risk pathologic features including high-grade disease, multifocality, and nodal involvement as well as worse recurrence free survival (RFS) with no impact on OS. We did not find a significant association between CIS and oncologic outcomes in a subset of patients who received NAC including those with down-staging to ≤ pT1 disease. In multivariate analysis, CIS had no association with either recurrence free or OS. Concomitant CIS in radical cystectomy specimens is associated with decreased RFS; however, in multivariate analysis, it was not an independent predicting factor of oncologic outcomes. Moreover, the impact of CIS on oncologic outcomes in a subset of patients who received NAC was insignificant.

Establishing the prediction models for recurrence and progression of T1G3 bladder urothelial carcinoma.

We aim to determine clinical recurrence and progression risk factors of T1G3 bladder cancer (BCa), and to establish recurrence and progression prediction models. 5-year follow-up records of 106 T1G3 BCa patients from January 2012 to December 2016 were analyzed for recurrence and progression. Two-sample T-test, Chi-square test, Mann-Whitney test, Kaplan-Meier curves, Cox univariate and multivariate analyses were performed to determine the independent risk factors. Effective prognostic nomograms were established to provide individualized prediction, and the calibration curves were founded to evaluate the agreements of the predicted probability with the actual observed probability. Receiver operating characteristic (ROC) curves were generated for the recurrence and progression prediction models. The stability of prediction models was validated with an external cohort included 61 T1G3 BCa patients. Of the 106 T1G3 BCa patients, 77 were males (72.6%) and 29 were females (27.4%), with median age 70 years. Within 5 years, recurrence was identified in 67 cases (63.2%), and progression was identified in 31 cases (29.2%). The results showed that large size of tumor, multifocal tumors, recrudescent tumor, non-BCG perfusion therapy were the independent risk factors for recurrence, and large size of tumor, multifocal tumors, recrudescent tumor, concomitant carcinoma in situ (CIS) were the independent risk factors for progression. However, no evidence shown that tumor location or operative method was independent risk factors for recurrence and progression. Based on the results of Cox regression analyses, the independent risk factors were used to establish the prediction nomograms to calculate the recurrence and progression probability of each T1G3 BCa patient. Calibration curves, ROC curves and external validation displayed that the nomograms had great value of prediction.

Should intravesical Bacillus Calmette–Guerin (BCG) treatment be administered to patients with T0 after repeat transurethral resection of bladder tumor in patients with high-risk non-muscle invasive bladder cancer?

We evaluated the effect of intravesical Bacillus Calmette–Guerin (BCG) and BCG maintenance therapy on the prognosis of patients with T0 after repeat transurethral resection of bladder mass (TURBT). This retrospective analysis involved 427 patients who underwent repeat TURBT within 6 weeks after initial TURBT from 2007 to 2016. Repeat TURBT was performed in patients with high-risk criteria. Patients who achieved T0 after repeat TURBT did or did not receive intravesical BCG therapy. Patients were divided into three groups: non-BCG, BCG induction, and BCG maintenance groups. The study included 106 patients who achieved T0 after repeat TURBT. The median follow-up was 63 months. There were no significant differences in T stage among the three groups. High grade ratio (p = 0.001) and concomitant CIS ratio (p = 0.037) were significantly higher in the BCG maintenance than in the other two groups. The recurrence rates in the non-BCG, BCG induction, and BCG maintenance groups were 46.2%, 28.3%, and 19.2%, respectively (p = 0.043). Recurrence-free survival was significantly higher in the BCG maintenance group than in the BCG induction group (p = 0.032). Progression-free survival was also higher in the BCG maintenance group than in the BCG induction group, but the difference was not significant (p = 0.056). Multivariate Cox regression analysis showed that only intravesical BCG maintenance therapy was significantly associated with recurrence (hazard ratio 0.016, p = 0.016). In high risk NMIBC patients, intravesical BCG maintenance treatment is required even at T0 after repeat TURBT. Intravesical BCG maintenance therapy of patients with T0 after TURBT reduces recurrence.

Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer – a follow-up five years after the start of treatment

Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations.Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients’ life.Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being.Conclusion: Patients with bladder cancer T1G2–G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient’s well-being. It is important to record the patients’ baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

Strong Expression of Cancertestis Antigens CTAG1B and MAGEA3 Is Correlated with Unfavourable Histopathological Features and MAGEA3 Is Associated with Worse Progression-Free Survival in Urothelial Bladder Cancer

Background: Cancer/testis antigens (CTA) are expressed in urothelial bladder cancer (UBC). Their therapeutical and prognostic relevance remains unclear. We studied the correlation of MAGEA3 and CTAG1B with histopathological factors in UBC and their prognostic value. Methods: Retrospective analysis of 93 patients who underwent treatment for UBC was conducted. Besides clinical and histopathological parameters, the expression of MAGEA3 and CTAG1B was assessed by immunohistochemistry. Results: Median follow-up was 75 months. Fifteen per cent of patients showed strong positive reaction to MAGEA3 staining. These tumours were statistically and significantly more often correlated with unfavourable World Health Organization (WHO) grading (G1: 0%, G2: 10.3%, G3: 23.4%, p = 0.048; low grade 0%, high grade 18.4%, p = 0.046 respectively). Correlation of CTAG1B with WHO grading was impressive with strong expression in no G1, 31.1% of G2 and 51.1% of G3 tumours (low grade 0%, high grade 43.4%, p = 0.001, respectively). Concomitant carcinoma in situ (Cis) was associated with strong CTAG1B expression (54.2% in concomitant Cis vs. 29% without concomitant Cis, p = 0.026). Kaplan-Meier analysis revealed statistically and significantly worse 5 years progression-free survival (PFS) associated with a strong expression of MAGEA3 (59 vs. 84%, p = 0.032). Conclusions: Strong CTA expression was correlated with unfavourable histopathological features. A strong expression of MAGEA3 was statistically and significantly associated with worse PFS across all stages of UBC.

A risk-stratified approach to the management of high-grade T1 bladder cancer.

A bladder-preserving approach for high-grade nonmuscle invasive bladder cancer that has invaded the lamina propria (T1HG) may result in increased recurrence, progression, and even death from bladder cancer in some patients. Initial radical cystectomy does have increased cancer-specific survival (CSS), but represents significant overtreatment for many patients. An evidence-based, risk-stratified approach is required to select patients for immediate radical cystectomy in order to improve CSS. A restaging transurethral resection aids in optimal staging and treatment of T1HG. Intravesical Bacillus Calmette-Guerin induction followed by 3 years of maintenance is the standard adjuvant management. However, when very high-risk (hydronephrosis, abnormal bimanual examination, variant histology, lymphovascular invasion, or residual disease on re-resection, and Bacillus Calmette-Guerin failure or early recurrence) or multiple high-risk factors (concomitant CIS, size >3 cm, multifocality, unfavorable tumor location, extensive lamina propria invasion, and elderly) are present, the risk of progression often outweighs the risk associated with radical cystectomy. In these cases, an immediate radical cystectomy likely provides an improved opportunity for cure compared to a bladder-preserving strategy. In order to increase the CSS of patients diagnosed with T1HG bladder cancer, an aggressive approach may benefit those with increased risk of progression.

Evaluation of Intraoperative Versus Postoperative Adjuvant Mitomycin C with Nephroureterectomy for Urothelial Carcinoma of the Upper Urinary Tract.

Background:Results of randomized trials support a single dose of intravesical chemotherapy following radical nephroureterectomy (RNU) for urothelial carcinoma.Objective:To evaluate the impact of the timing of intravesical mitomycin C (MMC) administration on the rate of bladder tumor recurrence (BTR) following RNU.Methods:We performed a retrospective review of patients who underwent RNU for upper tract urothelial carcinoma (UTUC) and received intravesical MMC between 2008 and 2016. Patients were categorized into two separate groups based on the timing of MMC administration: patients who received MMC intraoperatively (IO) and patients who received MMC on post-operative day 1 or later (PO). Our primary endpoint was BTR rate within the first year after surgery.Results:Fifty-one patients met our inclusion criteria: (IO: n = 30; PO: n = 21). There were no statistically significant differences in baseline characteristics of age, gender, race, surgical approach, tumor grade, tumor stage, surgical margins, nodal status, concomitant CIS, or history of bladder cancer. The median length of follow-up for each group was 22 months for IO and 12 months for PO (P = 0.10). The estimated probability of 1-year BTR rates for the IO and PO groups were 16% and 33%, respectively (p = 0.09). Cox analysis noted that the IO patients had a significantly lower rate of BTR in the first year postoperatively (HR = 0.113, 95% CI = 0.28–0.63, p = 0.01).Conclusions:The use of intraoperative MMC at the time of RNU was associated with a decrease in the risk of 1-year recurrence within the bladder.