Chemotherapy For Bladder Cancer Research Articles

Retrospective Analysis of a Cohort of Patients with Metastatic Bladder Cancer with Metastatic Sites Limited to the Pelvis and Retroperitoneum Treated at a Single Institution between 2009 and 2020.

Bladder cancer (BC) presenting with pelvic and retroperitoneal lymph nodes presents a therapeutic challenge. The impact of chemoradiotherapy on pelvic and retroperitoneal lymph node metastasis as a consolidation treatment has not been established. Between 2009 and 2020, 502 patients who were treated with first-line chemotherapy for BC in our center, were retrospectively identified. Patients who received chemoradiotherapy or radiotherapy with an equivalent radiation dose superior to 30 Gy were included in the RTCT group, and other patients were included in the control group (CT group). We performed an analysis of progression-free survival (PFS) and overall survival (OS) for these two cohorts using the Kaplan-Meier method. A total of 89 patients were included, 24 in the RTCT group and 65 in the CT group. Chemoradiotherapy improved both OS (p = 0.034) and PFS (p = 0.009) in comparison with chemotherapy alone: 26.3 months (95% IC 0.0-52.9) and 19.4 months (95% IC 5.0-33.7), respectively, in the RTCT group versus 17.2 months (95% IC 13.7-20.6) and 11.2 months (95% IC 8.6-13.8), respectively, in the CT group. Grade 3/4 toxicity was related to chemotherapy and to chemoradiotherapy at levels of 31% and 24%, respectively. For mBC with metastatic regional or retroperitoneal lymph nodes, chemoradiotherapy seems to confer benefits for both OS and PFS.

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.

KRT13-expressing epithelial cell population predicts better response to chemotherapy and immunotherapy in bladder cancer: Comprehensive evidences based on BCa database

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) has revolutionized bladder cancer (BCa) treatment. Patients likely to benefit from these therapies need to be accurately stratified; however, this remains a major clinical challenge. In the present study, single-cell RNA sequencing was used to evaluate the predictive ability of an epithelial cell population highly expressing keratin 13 (KRT13) to assess therapeutic response in BCa. The presence of KRT13-enriched tumors indicated favorable outcomes after NAC and superior response to ICT in patients with BCa. Furthermore, KRT13 population characteristics appeared to be closely related to changes in the immune microenvironment in the vicinity of this cell population. We constructed a prognostic model using an artificial neural network based on the gene signatures in the KRT13 population; the model demonstrated strong robustness and superiority. Additionally, a user-friendly and open-access web application named BCa database was developed for researchers to study BCa by mining the connective map database.

Refining the Characterization and Outcome of Pathological Complete Responders after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Lessons from the Randomized Phase III VESPER (GETUG-AFU V05) Trial.

Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy and pelvic lymph node dissection is the optimal treatment for patients with muscle-invasive bladder cancer. In recent years, the VESPER trial showed a statistically significant higher progression-free survival with dd-MVAC (dose dense methotrexate, vinblastine, doxorubicin, and cisplatin) compared to GC (gemcitabine and cisplatin). In the present report, we refine the characterization and outcome of patients whose cystectomy specimens were pathologically free of cancer (pathological complete response, pCR). We confirm that these patients portend a better outcome as compared to patients with invasive disease (≥pT1N0) at cystectomy. Nested variant and lymphovascular invasion were identified as adverse predictive factors of pCR. Progression-free survival probability three years after pCR on cystectomy was about 85%, regardless of the NAC regimen. A lower creatinine clearance and the delivery of less than four cycles were associated with a higher risk of relapse. Predicting the efficacy of NAC remains a major challenge. The planned analysis of molecular subtypes in the VESPER trial could help predict which patients may achieve complete response and better outcome.

Does care fragmentation in patients with bladder cancer lead to worse outcomes?

Care fragmentation may influence oncologic outcomes. The impact of care fragmentation on the outcomes of patients receiving neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is not well defined. We aimed to compare outcomes between patients who received fragmented care (FC) versus non-fragmented care (NFC). The National Cancer Database was queried for adult (≥18 years old) patients with cT2-T4aN0M0 urothelial carcinoma of the bladder receiving NAC followed by RC between 2004 and 2017. Patients were dichotomized based on whether they received FC (defined as receiving NAC at a different facility from where RC was performed) or NFC (defined as receiving NAC and RC at a single facility). The main outcome of interest was overall survival (OS). Secondary outcomes included time from diagnosis to treatment (NAC and RC) and perioperative outcomes. Kaplan-Meier survival estimates were calculated after stratifying by type of care received. Multivariable Cox regression analysis was performed to evaluate the association between FC and OS in the context of other clinically relevant covariates. A total of 2223 patients were included: 1035 (46.6%) received FC whereas 1188 (53.4%) received NFC. Factors associated with FC included greater travel distance, higher comorbidity burden, and surgical treatment at a high-volume facility. Patients who received FC had a slightly longer median time to RC (160 vs. 154 days, P = 0.001). However, on Kaplan-Meier analysis no differences in median OS were found between the two groups. On multivariable Cox regression analysis, factors associated with worse OS included age, advanced TNM stage, lymphovascular invasion, and positive surgical margins; yet FC was not associated with worse OS (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.88-1.17). On subgroup analysis, we found that FC received at academic facilities (HR 0.76; 95% CI 0.58-0.99), as well as NFC received at high-volume centers (HR 0.65; 95% CI 0.43-0.98), were associated with a decrease in overall mortality. Fragmented care is not associated with worse survival outcomes in patients with MIBC receiving NAC followed by RC.

Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.

548 Background: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. Methods: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher’s exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. Results: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). Conclusions: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Phase 2 open label study of durvalumab with neoadjuvant chemotherapy in variant histology bladder cancer.

524 Background: The immune-responsive nature of bladder cancer has made it an active area of interest for novel applications of immune checkpoint inhibitors (ICIs), with multiple ICI agents approved in the metastatic setting and ongoing perioperative trials. Variant histology urothelial carcinoma is a rare, heterogenous, and aggressive disease category associated with poor prognosis and response to standard therapies. This investigator-initiated phase 2 trial explored the addition of durvalumab to neoadjuvant chemotherapy (NAC) in the setting of variant histology MIBC. Methods: Patients with cT2-T4a, N0-N1, M0 histologically-confirmed bladder cancer of variant histology who were candidates for platinum-based NAC and radical cystectomy were eligible for the study. Enrolled patients received durvalumab with each cycle of investigator’s choice of platinum NAC (ddMVAC, cisplatin/gemcitabine, or carboplatin/gemcitabine). The primary objective was to determine the safety and tolerability of each study treatment as assessed by the total number of adverse events of grade 3 or higher, judged by the investigator as probably or definitely related to durvalumab. Secondary objective was to determine the percent of subjects post neoadjuvant chemo immunotherapy who achieve tumor stage of pT2N0M0 or better at cystectomy. Target accrual was 24 patients. Results: Six patients were enrolled (the study closed early due to low accrual). Median age was 72 years, 17% were women, 67% were white, 33% were Asian. 50% received ddMVAC and 50% received carboplatin/gemcitabine. All patients completed the planned cycles of NAC and durvalumab (4 cycles) and 5/6 proceeded to radical cystectomy (one patient declined cystectomy). Three patients experienced a Grade 3 AE that was assessed by the investigator to be related to treatment (table). One patient with sarcomatoid and glandular histology had pathological complete response and one patient with papillary and 10% squamous had pT2N0 at cystectomy. Conclusions: The addition of durvalumab to platinum NAC for patients with variant-histology muscle invasive bladder cancer demonstrates a reasonable safety and tolerability profile. Further investigation into this combination is warranted in larger scale trials. Clinical trial information: NCT03912818 . [Table: see text]

Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.

477 Background: First-line therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemo-immunotherapy trials failed to show a clear benefit over chemotherapy alone. We sought to use real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy or combination chemo-immunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). Methods: We used the National Cancer Database to identify patients with stage IV UCB diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt. An extension of inverse probability treatment weighting (IPTW) obtained from multinomial logistic regression was used to balance clinical and sociodemographic differences between treatment groups. Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. Results: A total of 4,169 patients were identified in the cohort; 3,255 (78.1%) were treated with chemotherapy, 601 (14.4%) with immunotherapy, and 313 (7.5%) with combination treatment. Multivariable analysis identified increasing age (RRR: 1.07, 95% CI, 1.06-1.08), comorbidity burden (Charlson-Deyo 2, RRR: 1.65, 95% CI, 1.21-2.24 and Charlson-Deyo 3, RRR: 2.11; 95% CI, 1.51-2.93), and treatment at an academic facility (RRR: 1.26; 95% CI, 1.03-1.53) as independent predictors of receiving immunotherapy. Treatment at an academic facility (RRR: 1.29, 95% CI, 1.01-1.65) was associated with receipt of combination treatment. After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95% CI, 0.62-0.83), but not immunotherapy alone, was associated with improved survival compared to chemotherapy. These data are limited by inability to determine platinum eligibility, and residual confounding. Conclusions: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Modest real-world utilization of chemo-immunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy. The study is limited by retrospective design; prospective data are necessary to identify patients who may benefit from combination chemo-immunotherapy.

FDG PET-CT imaging in assessing interim response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle invasive bladder cancer (MIBC): A prospective study.

460 Background: Muscle invasive bladder cancer (MIBC) is an aggressive local disease where initial staging with conventional CT imaging is often suboptimal. To explore the role of PET-CT in both staging MIBC and assessing response to neoadjuvant chemotherapy (NAC), we conducted a prospective multicentre, randomized trial known as PETMUSE. We report here the first results from the neoadjuvant substudy which assessed interim PET-CT response after 2-3 cycles of NAC and how this correlated with disease free survival (DFS) and overall survival (OS). Methods: Patients with MIBC (T2a-4a, N0-3, M0) based on transurethral resection of their bladder tumor and CT staging were randomized 2:1 to PET-CT or no PET-CT. All PET-CT patients, receiving cisplatin-based NAC underwent a second PET-CT after 2 cycles of gemcitabine and cisplatin (GC) or 3 cycles of dose dense methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) to assess for interim response. Patients were scored (1-5) by 2 independent reviewers according to the extent of metabolic response on PET-CT. Disease-free survival (DFS) and overall survival (OS) were collected. Results: Between 2016 and 2021, 291 patients were enrolled on PETMUSE of which 46 participated in the neoadjuvant substudy. Median age was 68 (51-86); 36 (78%) were male; 26 were ECOG 0 (57%); 31 (68%) were T2, 13 (28%) were T3/T4; and 35 (76%) were node negative. In terms of NAC regimens: 22 (48%) received GC, 17 (37%) split dose GC, 6 (13%) ddMVAC, and 1 (2%) MVAC. On PET-CT, 23 (50%) had a complete metabolic response, 14 (30%) had a partial metabolic response, 5 (11%) had no change or mixed response and 4 (9%) had progressive disease or new lesion on PET scan. Metabolic response on PET-CT was a statistically significant prognostic factor for both DFS and OS (see Table). Conclusions: In MIBC patients receiving cisplatin-based NAC, metabolic response seen on interim PET-CT was correlated with DFS and OS. PET-CT warrants further study in this setting as a potential early indicator of response to NAC. Clinical trial information: NCT02462239 . [Table: see text][Table: see text]

Pathologic response with neoadjuvant chemotherapy, immunotherapy, and chemo-immunotherapy for muscle-invasive bladder cancer (MIBC): A systematic review and meta-analysis.

531 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) is established in the management of MIBC. Pathologic complete response (pCR, ypT0N0) and downstaging (<ypT2N0) are associated with long term survival in patients with MIBC. Several trials have evaluated neoadjuvant immunotherapy (NAI) and chemoimmunotherapy (NACI) for MIBC. We aimed to conduct a meta-analysis of available trials to compare the incidence of pathological response with NAC, NAI and NACI in MIBC patients undergoing radical cystectomy. Methods: Phase II/III clinical trials assessing neoadjuvant systemic therapies (NAC, NAI, or NACI) in patients with MIBC undergoing radical cystectomy were identified through a systematic search of MEDLINE and EMBASE. Outcomes of interest included pCR and pathological downstaging. A DerSimonian and Laird random-effect meta-analysis was conducted to estimate pooled incidence of events using the Freeman-Tukey transformation. Clopper-Pearson method was used to estimate the associated 95% confidence intervals (CI). Results: Of the 5357 records initially identified, 28 trials with a total of 2138 patients were considered eligible for inclusion. Neoadjuvant chemotherapy was assessed in 15 trials (1535 patients), NAI in 5 (288 patients), and NACI in 8 (315 patients). The pooled incidence of patients experiencing a pCR was 30.91% (95% CI: 26.54%-35.45%) with NAC, 30.92% (23.22%-39.14%) with NAI, and 42.25% (36.6%-48.0%) with NACI. The difference in pCR among these therapies was statistically significant (p <0.05). Similarly, the pooled incidence of achieving pathological downstaging was 40.91% (34.26%-47.72%) with NAC, 38.84% (26.73%-51.64%) with NAI, and 62.88% (57.22%-68.39%) with NACI. Consistently, there was statistically significant effect modification by the choice of neoadjuvant systemic therapy (p <0.01). The results were consistent across different clinically important subgroups (Table). Conclusions: NACI may achieve better pCR and pathological downstaging than NAC and NAI alone in MIBC patients which may potentially be associated with long-term survival. Definitive data from phase III trials are pending. [Table: see text]

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 > 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 .

Approaches to Clinical Complete Response after Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer: Possibilities and Limitations

In the surgical oncology field, the change from a past radical surgery to an organ preserving surgery is a big trend. In muscle-invasive bladder cancer treatment, neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC) patients eligible for cisplatin. There is a growing interest in bladder preserving strategies after NAC because good oncologic outcome has been reported for pathologic complete response (pCR) patients after NAC, and many studies have continued to discuss whether bladder preservation treatment is possible for these patients. However, in actual clinical practice, decision-making should be determined according to clinical staging and there is a gap that cannot be ignored between clinical complete response (cCR) and pCR. Currently, there is a lack in a uniform approach to post-NAC restaging of MIBC and a standardized cCR definition. In this review, we clarify the gap between cCR and pCR at the current situation and focus on emerging strategies in bladder preservation in selected patients with MIBC who achieve cCR following NAC.

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.

Evaluation of thermal dose effect in radiofrequency-induced hyperthermia with intravesical chemotherapy for nonmuscle invasive bladder cancer

Purpose In nonmuscle invasive bladder cancer (NMIBC) patients who fail standard intravesical treatment and are unfit or unwilling to undergo a radical cystectomy, radiofrequency (RF)-induced hyperthermia combined with intravesical chemotherapy (RF-CHT) has shown promising results. We studied whether higher thermal dose improves clinical NMIBC outcome. Methods and materials The cohort comprised 108 patients who started with RF-CHT between November 2013 and December 2019. Patients received intravesical mitomycin-C or epirubicin. Bladder hyperthermia was accomplished with an intravesical 915 MHz RF device guided by intravesical thermometry. We assessed the association between thermal dose parameters (including median temperature and Cumulative Equivalent Minutes of T50 at 43 °C [CEM43T50]) and complete response (CR) at six months for patients with (concomitant) carcinoma in situ (CIS), and recurrence-free survival (RFS) for patients with papillary disease. Results Median temperature and CEM43T50 per treatment were 40.9 (IQR 40.8–41.1) °C and 3.1 (IQR 0.9–2.4) minutes, respectively. Analyses showed no association between any thermal dose parameter and CR or RFS (p > 0.05). Less bladder spasms during treatment sessions was associated with increased median temperature and CEM43T50 (adjusted OR 0.01 and 0.34, both p < 0.001). Conclusions No significant association between thermal dose and NMIBC outcome was found. Possibly thermal dose effect in patients of the current cohort exceeds a certain threshold value. On the other hand, occurrence of bladder spasms had a thermal dose limiting effect. We advise to treat patients with temperatures >40.5 °C for at least 45 min while respecting individual tolerability, including occurrence of bladder spasms.

Oncological outcomes of patients with node positive disease following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: A study of the EAU Young Academic Urologists urothelial carcinoma working group

Oncological outcomes of patients with node positive disease following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: A study of the EAU Young Academic Urologists urothelial carcinoma working group

Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer.

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observedin vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in bothin vitroandin vivo.In addition, IHC staining is used to analyze IFN-γ, TGF-β1, and TNF-α. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer – the Northern Irish Experience

Purpose: An analysis of neoadjuvant chemotherapy delivery and outcomes for patients with muscle-invasive bladder cancer prior to radical cystectomy. Neoadjuvant chemotherapy is associated with a 5 year 5% overall survival benefit in selected patients [1].

Incidence of Venous and Arterial Events in Patients Treated with Neoadjuvant Cisplatin-based Chemotherapy for Bladder Cancer and Predictability of Events using Khorana and Adapted HADVAS Score: a Large Retrospective Study across Three Centres in Scotland

Purpose: This study was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in patients with bladder cancer treated with neoadjuvant cisplatin-based chemotherapy and to analyse the prognostic baseline and treatment characteristics using Khorana and adapted HADVAS score in predicting TEE occurrences.

Factors predicting pathological complete response to neoadjuvant chemotherapy in patients diagnosed with non-metastatic muscle invasive urothelial bladder cancer

Aim: In this study, we aimed to investigate the factors that may have the potential to predict pathological complete response (pCR) with platinum-based neoadjuvant chemotherapy (NAC) in non-metastatic muscle-invasive bladder cancer (MIBC).Methods: Our study included 46 patients diagnosed with non-metastatic MIBC, who applied to Dicle University Medical Oncology Clinic between 2016-2019 years and received NAC. Age, gender, ECOG performance score, tumor grade, pathological tumor (pT) stage, clinical lymph node (cN) status, localization of the primary tumor in the bladder, presence of comorbid diseases, renal failure status, hydronephrosis, and NAC regimens were analyzed.Results: Of the total 46 patients included in the study, 42 (81.3%) were male and 4 (8.7%) were female. The median age at diagnosis was 61.5 (34-77) years. In the group of patients aged

Upregulation of MTHFD2 is associated with PD‑L1 activation in bladder cancer via the PI3K/AKT pathway.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) has been implicated in the etiology of various human malignant tumors; however, its exact role in bladder cancer (BC) remains to be explored. Through reverse transcription‑quantitative PCR, western blotting and immunohistochemistry detection of BC tissue, combined with The Cancer Genome Atlas (TCGA) database analysis, the present study demonstrated that MTHFD2 was upregulated in BC tissues. MTHFD2 expression in patients with BC was frequently associated with worse prognosis, tumor immune cell infiltration and programmed death‑ligand 1 (PD‑L1) expression. Subsequently, using short hairpin RNA, the expression levels of MTHFD2 were knocked down in BC cell lines, and the results revealed that the tumor cell proliferation and colony formation abilities of cells were greatly reduced, as determined by Cell Counting Kit 8 and colony formation assays, as was the expression of PD‑L1, as determined by western blotting. These findings were also confirmed in a xenograft nude mouse model. Simultaneously, it was revealed that abnormal expression of MTHFD2 was closely associated with the PI3K/AKT signaling pathway in both RNA‑sequencing and TCGA datasets. This observation was verified in vitro by detecting the protein expression levels of PI3K and AKT by western blotting. The activation of PI3K and AKT was enhanced in BC cells (T24) following stimulation with 740Y‑P, a PI3K activator, and cellular activities and PD‑L1 expression levels were restored. Finally, it was demonstrated that the MTHFD2 levels were correlated with chemosensitivity to traditional BC chemotherapeutic agents and various PI3K/AKT‑targeted drugs, as determined by analyzing the Genomics of Drug Sensitivity in Cancer database. Overall, the present findings revealed that upregulation of MTHFD2 was associated with PD‑L1 activation in BC via the PI3K/AKT signaling pathway, suggesting that it could be a promising marker of chemotherapy and immunotherapy for BC.