Neoadjuvant Chemotherapy For Bladder Cancer Research Articles

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer

The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR=1.193, 95% CI: 1.046-1.361, P=0.008) and CSS (HR=1.337, 95% CI: 1.139-1.569, P<0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

A bibliometric insight into neoadjuvant chemotherapy in bladder cancer: trends, collaborations, and future avenues.

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the cornerstone of treatment for muscle-invasive bladder cancer (MIBC). While platinum-based regimens have demonstrated benefits in tumor downstaging and improved long-term survival for selected patients, they may pose risks for those who are ineligible or unresponsive to chemotherapy. We undertook a bibliometric analysis to elucidate the breadth of literature on NAC in bladder cancer, discern research trajectories, and underscore emerging avenues of investigation. A systematic search of the Web of Science Core Collection (WoSCC) was conducted to identify articles pertaining to NAC in bladder cancer from 1999 to 2022. Advanced bibliometric tools, such as VOSviewer, CiteSpace, and SCImago Graphica, facilitated the examination and depicted the publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and salient keywords, emphasizing the top 25 citation bursts. Our analysis included 1836 publications spanning 1999 to 2022, indicating a growing trend in both annual publications and citations related to NAC in bladder cancer. The United States emerged as the predominant contributor in terms of publications, citations, and international collaborations. The University of Texas was the leading institution in publication output. "Urologic Oncology Seminars and Original Investigations" was the primary publishing journal, while "European Urology" boasted the highest impact factor. Shariat, Shahrokh F., and Grossman, H.B., were identified as the most prolific and co-cited authors, respectively. Keyword analysis revealed both frequency of occurrence and citation bursts, highlighting areas of concentrated study. Notably, the integration of immunochemotherapy is projected to experience substantial growth in forthcoming research. Our bibliometric assessment provides a panoramic view of the research milieu surrounding neoadjuvant chemotherapy for bladder cancer, encapsulating the present state, evolving trends, and potential future directions, with a particular emphasis on the promise of immunochemotherapy.

Meticulous initial clinical and pathological staging with standardized long-term follow-up after radical cystectomy is required to validate and improve overall prognostic performance in patients undergoing neoadjuvant chemotherapy for bladder cancer.

Meticulous initial clinical and pathological staging with standardized long-term follow-up after radical cystectomy is required to validate and improve overall prognostic performance in patients undergoing neoadjuvant chemotherapy for bladder cancer.

Oncological outcomes of visibly complete transurethral resection prior to neoadjuvant chemotherapy for bladder cancer.

To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (<ypT2N0), with complete pathologic response (ypT0N0) and survival as secondary endpoints. Logistic regression and Cox proportional hazards models were utilized. We identified 153 patients, including 116 (76%) with a complete TURBT. Sixty-four (42%) achieved <ypT2N0 and 43 (28%) achieved ypT0N0. When comparing those with and without a complete TURBT, there was no significant difference in the proportion with <ypT2N0 (43% vs 38%, P=0.57) or ypT0N0 (28% vs 27%, P=0.87). After median follow-up of 3.6 years (IQR 1.5-5.1), 86 patients died, 37 died from bladder cancer, and 61 had recurrence. We did not observe a statistically significant association of complete TURBT with cancer-specific or recurrence-free survival (p≥0.20), although the hazard of death from any cause was significantly higher among those with incomplete TURBT even after adjusting for ECOG and pathologic T stage, HR 1.77 (95% CI 1.04-3.00, P=.034). A visibly complete TURBT was not associated with pathologic downstaging, cancer-specific or recurrence-free survival following NAC and RC. These data do not support the need for repeat TURBT to achieve a visibly complete resection if NAC and RC are planned.

MP46-05 GENDER, RACIAL AND ETHNIC DIFFERENCES IN PATHOLOGIC RESPONSE FOLLOWING NEOADJUVANT CHEMOTHERAPY FOR BLADDER CANCER PATIENTS

You have accessJournal of UrologyCME1 Apr 2023MP46-05 GENDER, RACIAL AND ETHNIC DIFFERENCES IN PATHOLOGIC RESPONSE FOLLOWING NEOADJUVANT CHEMOTHERAPY FOR BLADDER CANCER PATIENTS Irasema Paster, Jiping Zeng, Alejandro Recio-Boiles, and Juan Chipollini Irasema PasterIrasema Paster More articles by this author , Jiping ZengJiping Zeng More articles by this author , Alejandro Recio-BoilesAlejandro Recio-Boiles More articles by this author , and Juan ChipolliniJuan Chipollini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003292.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The purpose of this study was to evaluate nationwide trends in pathologic complete response (CR) racial variations in patients with muscle-invasive bladder cancer (MIBC) undergoing cystectomy. METHODS: The National Cancer Database was queried for patients from 2004 to 2016 with non-metastatic MIBC who underwent neoadjuvant chemotherapy and definitive surgery. The primary endpoints, CR and mortality, were evaluated using Cochran-Armitage test, multivariable regression, and Kaplan-Meier analyses. RESULTS: The final analytic cohort was 9,955 patients. Non-Hispanic black (NHB) patients presented with younger age (p<0.001), higher comorbidity score (p=0.036), and higher clinical tumor (cT) stage (p<0.001). The overall CR rate was highest for non-Hispanic white (NHW) males (13.4%) while Hispanic white (HW) females and NHB males had lower CR rates (both, 9.1%). There was a significant increase in CR trends for NHW patients (p<0.001), and non-significant increases for NHB (p=0.311) and Hispanic patients (p=0.236). On multivariable analysis, NHW females had significantly lower odds of achieving CR (OR; 0.83, 95%CI 0.71-0.97); however, NHB males (HR: 1.21, 1.01-1.44) and NHB females (HR: 1.25, 1.03-1.53) had higher overall mortality on adjusted analysis. Overall survival differences were not seen in patients who achieved CR regardless of racial background; however, for those with residual disease, the 2-year survival probabilities were 60.7, 62.5, and 51.1% for NHW, HW, and NHB patients, respectively (log-rank p=0.010). CONCLUSIONS: Our findings showed differences in chemotherapy response based on gender and race/ethnicity. The trends in CR for all racial/ethnic groups appear to be increasing over time. However, even after guideline-directed care, black patients were found with worse survival particularly when residual disease is present. Clinical studies with more underrepresented minorities are needed to verify biological differences in response and help mitigate potential socioeconomic disparities in MIBC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e632 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Irasema Paster More articles by this author Jiping Zeng More articles by this author Alejandro Recio-Boiles More articles by this author Juan Chipollini More articles by this author Expand All Advertisement PDF downloadLoading ...

Predictive Value of 18F-FDG PET/CT for Assessment of Tumor Response to Neoadjuvant Chemotherapy in Bladder Cancer.

The purpose of the current study was to evaluate the diagnostic accuracies of 18F-FDG PET/CT for prediction of tumor response to neoadjuvant chemotherapy in bladder cancer (BC) patients through a systematic review and meta-analysis. The PubMed, Cochrane database, and Embase database were searched from inception through November 30, 2022 for studies evaluating diagnostic performance of 18F-FDG PET/CT for prediction of tumor response to neoadjuvant chemotherapy in BC patients. Based on data extracted from patient-based and lesion-based analysis, we calculated the pooled sensitivity and specificity with the 95% confidence intervals (CIs). Also, we calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across 5 studies (12 results), the pooled sensitivity of 18F-FDG PET/CT was 0.84 (95% CI, 0.72-0.91), and the pooled specificity was 0.75 (95% CI, 0.59-0.86). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 3.3 (95% CI, 2.0-5.6) and negative likelihood ratio (LR-) of 0.22 (95% CI, 0.12-0.38). The pooled diagnostic odds ratio was 15 (95% CI, 7-36). The pooled sensitivity of 18F-FDG PET/CT for prediction of pathologic complete response was 0.68 (95% CI, 0.56-0.78), and the pooled specificity was 0.77 (95% CI, 0.60-0.88). The pooled sensitivity of 18F-FDG PET/CT for prediction of clinical response and nonresponse was 0.94 (95% CI, 0.85-0.98), and a pooled specificity was 0.73 (95% CI, 0.42-0.91). 18F-FDG PET/CT showed a good diagnostic performance for prediction of tumor response to neoadjuvant chemotherapy in BC patients.

A phase II trial of risk-enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN).

438 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy or chemoradiation is the standard of care for urothelial carcinoma (UC) patients with MIBC. Both cystectomy and chemoradiation have short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients prospectively for a cystectomy or chemoradiation avoidance algorithm. Methods: We conducted a single-arm, phase II, non-inferiority trial (NCT02710734) to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 UC underwent NAC with accelerated MVAC. Pre-NAC TURBT specimens were sequenced (Caris) for mutations in ATM, ERCC2, FANCC or RB1. Patients with ≥ 1 mutations and no clinical evidence of disease by restaging TUR, urine cytology and imaging post-NAC began pre-defined active surveillance (AS). Remaining patients underwent bladder-directed therapy. The primary endpoint was metastasis-free survival (MFS) at 2 years for the entire cohort. The risk-adapted approach would be declared non-inferior to the standard of care if the lower bound of an exact 1-sided 95% CI for MFS was &gt; 64%. The study required 70 patients with a 4.5% type I error and 81.6% power. Results: 71 (ITT) patients were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of MVAC with 17% grade 3-4 TRAEs. In the ITT population, 33 (46%) had a relevant mutation and 26 (37%) began AS. With a median follow-up of 41 months, 47 patients (66%) are metastasis-free (CI 54%-77%). The 2-year MFS for the ITT patients (primary endpoint) was 72% (lower bound exact 1-sided 95% CI=62%). On post hoc analysis, the 2-year MFS was 65% in the AS group (CI 44%-83%) and 76% (CI 60%-87%) in the remaining patients (P=0.42). In the AS group, 18 patients (69%) had some UC recurrence, 8 had a cystectomy, 2 chemoradiation, and 13 (50%) are metastasis-free with an intact bladder. Of the 10 patients (38%) on AS who developed metastatic disease, 9 recurred with localized disease first. The 2-year OS is 83% (CI 72%-90%) and 89% (CI 68%-96%) in the ITT and AS groups, respectively. Associations between mutation presence and MFS or UC recurrence were not observed. Conclusions: The 72% 2-year MFS rate in this MIBC cohort treated with a risk-adapted approach did not satisfy the pre-specified non-inferiority condition. 38% of AS patients developed metastatic disease, with most patients first recurring locally in the bladder. With a median follow-up of 41 months, although 50% of AS patients have been able to avoid cystectomy without metastatic disease, further refinement of this approach is necessary. Clinical trial information: NCT02710734 .

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Downstaging and survival after Neoadjuvant chemotherapy for bladder cancer in Norway; a population-based study

BackgroundNeoadjuvant chemotherapy (NAC) before radical cystectomy is associated with pathological downstaging (DS) and improved overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC). Population-based studies have not unequivocally shown improved survival. The aim of this population-based study was to evaluate the effect of NAC on DS and OS in Norwegian patients with MIBC.MethodsPatients in the Cancer Registry of Norway undergoing radical cystectomy (2008–2015) with or without NAC diagnosed with MIBC between 2008 and 2012 were included. Follow-up data were available until 31 December 2019. Logistic regression estimated the odds of DS with NAC, and a Cox model investigated the effect of DS on OS. Cox models, a mediator analysis and an instrumental variable approach were used to investigate the effect of NAC on OS.ResultsA total of 575 patients were included. NAC was administered to 82 (14%) patients. Compared to cystectomy only, NAC increased the proportion (43% vs. 22%) and the odds of DS (OR 2.51, CI 1.37–4.60, p = 0.003). Independent of NAC, the proportion of pN0 was higher in patients with DS (89% vs. 60%) and DS yielded a 78% mortality risk reduction (HR 0.22, CI 0.15–0.34, p = 1.9∙10–12), compared to patients without DS. We did not find an association between NAC and OS, neither by Cox regression (HR 1.16, CI 0.80–1.68, p = 0.417) nor by an instrumental variable approach (HR = 0.56, CI = 0.07–4.57, p = 0.586). The mediation analysis (p = 0.026) confirmed an indirect effect of NAC on OS through DS. Limitations include limited information of the primary tumour, details of NAC treatment and treatment indications.ConclusionsNAC increases the probability of DS and is indirectly associated to OS. DS is related to the absence of regional lymph node metastases and is associated with an OS benefit. Improved staging and biomarkers are needed to identify patients most likely to achieve DS and to benefit from NAC.

Quantitative multiparametric MRI as a promising tool for the assessment of early response to neoadjuvant chemotherapy in bladder cancer

PurposeMagnetic resonance imaging (MRI) has been applied to predict the neoadjuvant chemotherapy (NAC) response of bladder cancer at an early stage, but the performance remains poor. A tool for the selection of patients with muscle-invasive bladder cancer (MIBC) with high probability of benefitting from NAC is not yet available. We designed a prospective study to assess a quantitative MRI for predicting the early response of MIBC to NAC. MethodsAll individuals underwent a time-course MRI at pre-NAC, 24 h after initial cisplatin medication (24 h-NAC) and post-NAC.Chemosensitivity was evaluated according to pathological response.The transfer constant (Ktrans), plasma volume (Vp), extravascular extracellular space (Ve), and apparent diffusion coefficient (ADC) were quantitated based on dynamic contrast-enhanced and diffusion-weighted imaging.Quantitative RECIST criteria were constructed by modelling pre-NAC and 24 h-NAC MRI measures, and then compared with conventional RECIST by using pre- and post-NAC MRI measures. ResultsIn this pilot study, a total of 24 patients were enrolled into the study. Eight patients were pathologically confirmed to be NAC-responders. After a thorough evaluation of these parameters, different parameters showed good discrimination at different point in time. ROC curves showed quantitative MRI can predict the response to NAC, especially ADC_M (AUC = 0.859, P = 0.005) and ADC index (AUC = 0.844, P = 0.007) at pre-NAC timing and ADC_M (AUC = 0.816, P = 0.013) at 24 h-NAC timing. Then, a qRECIST model was established for predicting NAC sensitivity, with AUC of 0.91, TP rate of 0.8, and accuracy of 0.75. ConclusionThe diagnostic performance of mpMRI parameters for NAC response is excellent. The qRECIST derived between pre- and 24 h NAC MRI could predict the early response of MIBC to NAC and help for candidate selection.

EP030 - Prognostic significance of neutrophil to lymphocyte ratio in neoadjuvant chemotherapy in bladder cancer

EP030 - Prognostic significance of neutrophil to lymphocyte ratio in neoadjuvant chemotherapy in bladder cancer

IHC-Based Gene Expression Analysis Predicts Response to Neoadjuvant Chemotherapy for Bladder Cancer

Objectives: To explore the related genes and clinical characteristics of neoadjuvant chemotherapy (NAC) in bladder cancer, and to establish the prediction model of NAC response.Methods: We downloaded the clinical information and gene expression detected by IHC of 149 patients from the attachment of published paper. Patients were divided into three groups according to different pathological reactions of NAC.

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. Patient summaryIt is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.

Venous thromboembolism risk in patients receiving neoadjuvant chemotherapy for bladder cancer.

There is limited evidence to inform thromboprophylaxis use for patients receiving neoadjuvant chemotherapy prior to surgery in bladder cancer. We sought to determine the incidence of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy and cystectomy. We also assessed if the Khorana score was associated with VTE risk. A retrospective cohort study was performed on consecutive patients who received a radical cystectomy for bladder cancer at The Ottawa Hospital between January 2016 and August 2020. Demographic information, chemotherapy data, operative characteristics, VTE and bleeding outcomes were collected from the start of treatment to 90 days postoperative. A Khorana score was calculated for each patient who received neoadjuvant chemotherapy. The primary outcome for this study was the incidence of VTE from the time the patient started treatment with neoadjuvant chemotherapy until 90 days post-cystectomy. Secondary outcomes included risk factors for VTE during neoadjuvant chemotherapy. Among 181 radical cystectomy cases during the study period, 123 had muscle-invasive disease and 72 (39.8%) received neoadjuvant chemotherapy. Eighteen (25.0%) patients who received neoadjuvant chemotherapy and radical cystectomy developed a VTE from the start of chemotherapy to 90 days postoperative. Thirteen of the 18 VTEs (72%) occurred while the patient was receiving chemotherapy. In multivariable analysis, the only factor associated with a significantly increased risk of VTE was treatment with neoadjuvant chemotherapy (Relative risk (RR) 3.05, 95% confidence interval [CI] 1.16-8.02; P = 0.02). A higher Khorana score was not associated with an increased risk of VTE in patients who received neoadjuvant chemotherapy (RR = 0.33, 95% CI 0.08-1.28, P = 0.11). One (1.4%) patient had a major bleeding event during neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy and radical cystectomy are at very high-risk of VTE. Prospective studies that assess the benefits and harms of pharmacologic thromboprophylaxis in this population are needed.

A systematic review and meta-analysis of neoadjuvant chemotherapy for bladder cancer between ddMVAC and GC regimen.

The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) regimen and gemcitabine and cisplatin (GC) regimen as neoadjuvant chemotherapy choices for bladder cancer. A literature review of articles published before February 28, 2021, was conducted using the PubMed, Web of Sciences and Embase databases. Data for comparison included pathological response rate and overall survival. Five studies including 1,206 patients were identified and assessed for the meta-analysis. The pooled analysis yielded an odds ratio value of 1.29 (95% CI, 0.86-1.92) with a downstaging rate and an odds ratio value of 1.57 (95% CI, 1.10-2.25) with a complete response rate when comparing ddMVAC with the GC regimen. The pooled analysis yielded a hazard ratio of 0.47 (95% CI, 0.30-0.72) with regard to overall survival between the two regimens. Compared with the GC regimen, ddMVAC has a better pathological response rate, especially the complete response rate, and provides longer overall survival as a neoadjuvant chemotherapy regimen for bladder cancer.

Response to neoadjuvant chemotherapy in histologic variants of bladder cancer.

458 Background: Localized muscle invasive bladder carcinoma is mostly treated with neoadjuvant chemotherapy (NAC) before surgery in order to improve the outcome. Urothelial carcinoma (UC) is the most frequent histological type. Histological variants (pure or mixed) occur in 10% of bladder carcinoma. There is a lack of data on NAC efficacy for these histological subtypes. In this study, we evaluated the histologic response to NAC in the variant population of bladder cancer. Methods: Patients from 2 french hospitals (CHU de Nantes and ICM) treated with NAC for bladder cancer from 2010 to August 2021 were included in this retrospective study. We compared response to NAC between UC and histologic variants (pure or mixed) on cystectomy piece. The histological response was defined by the tumor downstaging after NAC (≤pT1Nx). We also collected the pathological complete response (pCR), which was defined by no residual tumor on the cystectomy piece. Results: 87 patients were included. 31 patients harbored a variant pattern: 7 squamous component, 3 adenocarcinoma component, 5 micropapillary component, 2 sarcomatoid component, 4 neuroendocrine carcinoma, 4 nest, 1 lymphoepithelial carcinoma, 2 giant cell, 1 undifferentiated, 1 micropapilallary and adenocarcinoma component and 1 adenosquamous component; 56 were conventional UC. NAC was MVAC in 77% of patient in the variant group, and 82% in the UC group. Others chemotherapy drugs were used as gemzar cisplatine, and platine etoposide. Downstaging was observed in 55% of patients in the variant group (17/31) and in 59% in the UC group (33/56). The difference was not statistically significant (p &lt;0,44). pCR was observed in 39% of patients in the variant group (12/31) and 43% in the UC group (24/56), the difference was not significant (p&lt; 0.44). Conclusions: NAC can be effective in the histologic variant population of bladder carcinoma, nevertheless these data could be confirmed in a larger cohort.

Research Progress in Neoadjuvant Chemotherapy for Bladder Cancer

Neoadjuvant chemotherapy is a systemic pre-operative treatment which can eliminate microscopic lesion of bladder cancer including metastatic lesion. It significantly improves 5-year survival rate of bladder cancer. For patients with non-organ-confined bladder cancer, neoadjuvant chemotherapy combined with radical cystectomy can be a better treatment option. This article covers the current status of bladder treatment and the rise of neoadjuvant chemotherapy, advantages and disadvantages of neoadjuvant chemotherapy, prediction of efficacy of neoadjuvant chemotherapy, the choices for neoadjuvant chemotherapy patient, improvement of neoadjuvant chemotherapy, and large-scale clinical trial of neoadjuvant chemotherapy for bladder cancer.

A longitudinal study evaluating interim assessment of neoadjuvant chemotherapy for bladder cancer.

To evaluate the usefulness of radiological re-staging after two and four cycles of neoadjuvant chemotherapy (NAC), the impact of re-staging on further patient management, and the correlation between clinical and final pathological tumour stage at radical cystectomy (RC). We conducted a longitudinal, single-centre, cohort study of prospectively collected consecutive patients who underwent NAC and RC for urothelial muscle-invasive bladder cancer between July 2001 and December 2017. Patients underwent repeated computed tomography scans for re-staging after two cycles of NAC and after completion of NAC before RC. Of 180 patients, 110 had ≥four cycles of NAC and had complete imaging available. In the entire cohort, further patient management was only changed in 2/180 patients (1.1%) after two cycles of NAC based on radiological findings. Patients who were stable after two cycles but then downstaged after at least four cycles of NAC had a similarly lowered risk of death (hazard ratio [HR] 0.53). Only one patient downstaged after two cycles was subsequently upstaged after four cycles. Clinical downstaging was observed in 51 patients (46%), 55 patients (50%) had no change in clinical stage and four patients (3.6%) were clinically upstaged. Patients clinically downstaged after four cycles of NAC had a lower risk of death (HR 0.49, 95% confidence interval 0.25-0.94; P = 0.033) compared to those with no change or upstaged after completion of NAC. Re-staging of muscle-invasive bladder cancer after two cycles of NAC offers little additional information, rarely changes patient management, and may therefore be omitted, whereas re-staging after completion of NAC by CT is a strong predictor of overall survival.

Analysis of the patients' quality of life after radical cystectomy with the orthotopic neobladder or ileal conduit formation

Introduction. Orthotopic neobladder or ileal conduit are the most optimal and common methods of intestinal urine diversion. Nevertheless, there is no consensus in the current literature as to which of these urine diversion techniques provides a better quality of life. Purpose of the study. To conduct a comparative study of the quality of life of patients who underwent radical cystectomy with the formation of an orthotopic neobladder or ileoconduit. Materials and methods. The study included 60 patients (46 men (76.6%) and 14 (23.4%) women) who underwent radical cystectomy (RCE) with intestinal urine diversion. The mean age of the patients was 66 (47 - 85) years. The exclusionary criteria for the study were: neoadjuvant chemotherapy for bladder cancer; preoperative ASA IV - V degree; RCE with intestinal urine diversion not for bladder cancer; the inability to fill out questionnaires assessing the postoperative aspects of the quality of life (QoL) for certain reasons. All patients were divided into 2 groups to allow comparative analysis: Group I — 26 patients (43.3%) underwent RCE with the formation of an orthotopic neobladder according to the Studer method; Group II — 34 patients (56.7%) underwent RCE with the formation of an ileal conduit according to Bricker. The median follow-up period for patients from the completed surgical procedure to the survey was 7 months (4.5 - 9.5 months). The monitoring of the postoperative patients' QoL after RCE was carried out based on the questionnaires: EORTC QLQ-C30, EORTC QLQ-BLM. Also, we carried out a retrospective comparative analysis of early postoperative complications and mortality after RCE in both groups due to Clavien-Dindo classification. Results. The mean time of surgery in Groups I was 280 ± 56.3 min, in Group II — 230 ± 60.8 minutes, (p = 0.117), median blood loss was 350 ml (283 - 380) in Group 1 with 270 (245 - 310) ml in Group 2 (p = 0.213). The frequency of complications according to Clavien-Dindo I - II in the Group 1 was observed in 11 (42.3%) patients, in the Group 2 in 12 (35.2%) patients (p = 0.579), complications according to Clavien-Dindo III - IV in the Group 1 were found in 5 (19.2%) patients while in the Group 2 in 7 (20.5%) patients (p = 0.896). The mortality rate was 8.3% (5 people) and there is no statistically significant difference in the mortality rate in both groups of patients (p = 0.241). Based on the analysis of the QLQ-C30 and QLQ-BLM questionnaire data, we noted that a total of «good» quality of life in the Group 1 was noted by up to 18 (69.2%) patients compared with the Group 2 in up to 15 (44.1%) patients (p &lt; 0.05). At the same time, the predominance of the QoL was observed on all the main scales of the QLQ-C30 questionnaire: the scale of physical condition, cognitive functions, emotional state and social adaptation. According to the results of the QLQ-C30 questionnaire, there were more financial in the group of patients with an ileal conduit. In the postoperative period, the following symptoms prevailed in both groups of patients: nausea, vomiting, weakness and pain. During the analysis of the functional results, we noted that in Group I,4 (15.3%) patients had nocturnal and daytime urinary incontinence, 2 (7.6%) patients required self-catheterization of the intestinal reservoir periodically, in Group II — 8 (23.5%) patients report urine leakage from the urostomy and skin dermatitis periodically. Conclusion. Despite the fact of worldwide recognition as a result of the preferences of surgeons in favour of the ileal conduit formation by the Bricker technique during RCE, urine diversion using orthotopic neobladder demonstrates better results with analysis of QoL in our patients. Obviously, long-term studies with a large sample of patients are required to obtain more reliable results of a QoL evaluation after RCE with intestinal urine diversion.

Neoadjuvant chemotherapy in bladder cancer: Clinical benefit observed in prospective trials computed with restricted mean survival times

PurposeNeoadjuvant chemotherapy (NAC) is the standard of care for eligible patients with cT2-4a N0 M0 bladder cancer undergoing surgical resection. The extent to which (and if) NAC increases patient survival is not clear as clinical trials and meta-analyses have generated both negative and “borderline” positive results. The novel method of calculating restricted mean survival times (RMST) may provide a more meaningful way to quantify treatment efficacy due to inherent statistical limitations of conventional hazard ratios. In this study we analyzed the survival benefit attributable to NAC in bladder cancer by calculating RMST of previously published clinical trials. Materials and methodsAll published randomized controlled clinical trials of bladder cancer with available survival data comparing NAC plus radical cystectomy with cystectomy alone were included. RMSTs were calculated for each cohort at the 5-year and total follow-up time periods, comparing the NAC and radical cystectomy groups. Fixed effect meta-analysis of the 5-year RMSTs was then performed to calculate the net impact of NAC on overall survival. ResultsFor 2 among 7 included trails, RMST analysis changed the statistical significance. The SWOG 8,710 trial that had previously suggested a survival benefit associated with NAC (P = 0.06) was found to have a clearer beneficial association by 5-year RMST (6.5 month benefit; P = 0.01) and total follow-up RMST (13.6 month benefit over 168 months; P = 0.04). The International Collaboration of Trialists trial that had previously suggested a survival benefit with NAC (P = 0.04) was found to have a beneficial association by total follow-up RMST (6.7 months benefit over 120 months; P = 0.04) but not 5-year RMST (P = 0.10). The interpretation of other trials did not change. Fixed effect meta-analysis suggested a clinically significant overall survival benefit associated with NAC (3.2 months benefit over 60 months; P < 0.01). ConclusionsEvaluation of published randomized controlled trials using RMSTs strengthens the association of neoadjuvant chemotherapy with survival benefit in bladder cancer. As RMST may enable improved detection of clinical benefit when compared to conventional statistical methods, consideration should be given to RMST-based endpoints in future clinical trial design.