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High-grade (HG) urothelial carcinoma (UC) with variant histology has historically been managed conservatively. The presented case details a solitary lesion of muscle-invasive bladder cancer (MIBC) with sarcomatoid variant (SV) histology treated by partial cystectomy (PC) and adjuvant chemotherapy. A 71-year-old male with a 15-pack year smoking history presented after outside transurethral resection of bladder tumor (TURBT). Computerized tomography imaging was negative for pelvic lymphadenopathy, a 2 cm broad-based papillary tumor at the bladder dome was identified on office cystoscopy. Complete staging TURBT noted a final pathology of invasive HG UC with areas of spindle cell differentiation consistent with sarcomatous changes and no evidence of lymphovascular invasion. The patient was inclined toward bladder-preserving options. PC with a 2 cm margin and bilateral pelvic lymphadenectomy was performed. Final pathology revealed HG UC with sarcomatoid differentiation and invasion into the deep muscularis propria, consistent with pathologic T2bN0 disease, a negative margin, and no lymphovascular invasion. Subsequently, the patient pursued four doses of adjuvant doxorubicin though his treatment was complicated by hand-foot syndrome. At 21 months postoperatively, the patient developed a small (

The incidence of bladder cancer (BC) depends on advancing age and other risk factors, significantly impacting on surgical, functional and oncological outcomes. Radical cystectomy (RC) with urinary diversion is the gold standard therapy for muscle invasive bladder cancer; however, it remains a complex surgery and requires careful analysis of risk factors in order to potentially decrease post-surgical complication rates. Age in surgery is a limiting factor that can modify surgical and oncological outcomes, and is correlated with a high rate of post-dimssion hospital readmissions. The reconstruction of the bladder with the intestine represents a crucial point of radical cystectomy and the urinary derivation (UD) is at the center of many debates. A non-continent UD seems to be the best choice in elderly patients (>75 years old), while orthotopic neobladder (ON) is poorly practiced. We reviewed the literature to identify studies reporting outcomes, complications, patient- selection criteria, and quality-of-life data on elderly patients, who underwent ON following radical cystectomy. Reviewing the literature there is no clear evidence on the use of age as an exclusion criterion. Certainly, the elderly patient with multiple comorbidities is not eligible for ON, preferring other UD or rescue therapies. A careful preoperative selection of elderly patients could greatly improve clinical, surgical and oncological outcomes, giving the chance to selected patients to receive an ON. [ABSTRACT FROM AUTHOR]

Purpose: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. Materials and Methods: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression‐free survival, and rehospitalization. Results: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression‐free survival (HR: 1.83, 95% CI: 1.12–3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99–3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). Conclusions: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life. [ABSTRACT FROM AUTHOR]

IntroductionMuscle-invasive bladder cancer (MIBC) is a heterogeneous disease with several taxonomic molecular subtypes showing different genetic, clinical, and epidemiological profiles. It has been suggested that MIBC-subtypes follow different tumorigenesis pathways playing decisive roles at different stages of tumor development, resulting in distinct tumor microenvironment containing both innate and adaptive immune cells (T and B lymphocytes). We aim to characterize the MIBC tumor microenvironment by analyzing the tumor-infiltrating B and T cell repertoire according to the taxonomic molecular subtypes.MethodsRNAseq data from 396 MIBC samples included in TCGA were considered. The subtype information was collected from the international consensus taxonomic classification describing six subtypes: Basal/Squamous-like (Ba/Sq), Luminal papillary (LumP), Luminal non-Specify (LumNS), Luminal unstable (LumU), Stroma-rich, and Neuroendocrine-like (NE-like). Using MiXCR, we mapped the RNA read sequences to their respective B-cell receptor (BCR) and T-cell receptor (TCR) clonotypes. To evaluate the BCR and TCR differences among subtypes, we compared diversity measures (richness and diversity) using a Wilcoxon test and we performed a network analysis to characterize the clonal expansion. For the survival analysis stratified by subtypes, Cox regression models adjusted for age, region, and pathological stage were performed.ResultsOverall, we found different patterns of tumor-infiltrating immune repertoire among the different MIBC subtypes. Stroma-rich and Ba/Sq tumors showed the highest BCR and TCR infiltration while LumP showed the lowest. In addition, we observed that the Ba/Sq and Stroma-rich tumors were more clonally expanded than the Luminal subtypes. Moreover, higher TCR richness and diversity were significantly associated with better survival in the Stroma-rich and Ba/Sq subtypes.DiscussionThis study provides evidence that MIBC subtypes present differences in the tumor microenvironment, in particular, the Ba/Sq and the Stroma-rich are related with a higher tumoral-infiltrating immune repertoire, which seems to be translated into better survival. Determining the causes of the different tumoral-infiltrating immune repertoire according to the MIBC molecular subtypes will help to improve our understanding of the disease and the distinct responses to immunotherapy of MIBC.

Introduction: This meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscleinvasive bladder carcinoma (MIBC). Materials and methods: Four databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade= 3 irAEs rate, RFS, and OS were performed. Results: In total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30-0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95% CI=0.19-0.35, p=0.1), 0.41 (95%CI=0.21-0.62, p=0.01), 0.43 (95%CI=0.35-0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46-0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22-0.51, p=0.01), 0.51 (95% CI=0.39-0.62, p=0.43), and 0.61 (95%CI=0.53-0.69, p=0.01), respectively. Kaplan-Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade= 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95% CI=0.09-0.22, p=0.00%). In subgroup analysis, the pooled result of Grade= 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L) 1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04-0.11, p=0.84), 0.31 (95% CI=0.16-0.47, p=0.06), and 0.17 (95%CI=0.06-0.31, I² = 71.27%, p=0.01), respectively. Conclusion: Neoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade=3 irAEs. Kaplan-Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups. [ABSTRACT FROM AUTHOR]

Objectives: To develop an MRI radiomic nomogram capable of identifying muscle invasive bladder cancer (MIBC) patients with high-risk molecular characteristics related to poor 2-year disease-free survival (DFS). Methods: We performed a retrospective analysis of DNA sequencing data, prognostic information, and radiomics features from 91 MIBC patients at stages T2-T4aN0M0 without history of immunotherapy. To identify risk stratification, we employed Cox regression based on TP53 mutation status and tumor mutational burden (TMB) level. Radiomics signatures were selected using the least absolute shrinkage and selection operator (LASSO) to construct a nomogram based on logistic regression for predicting the stratification in the training cohort. The predictive performance of the nomogram was assessed in the testing cohort using receiver operator curve (ROC), Hosmer–Lemeshow (HL) test, clinical impact curve (CIC), and decision curve analysis (DCA). Results: Among 91 participants, the mean TMB value was 3.3 mut/Mb, with 60 participants having TP53 mutations. Patients with TP53 mutations and a below-average TMB value were identified as high risk and had a significantly poor 2-year DFS (hazard ratio = 4.36, 95% CI 1.82–10.44, P < 0.001). LASSO identified five radiomics signatures that correlated with the risk stratification. In the testing cohort, the nomogram achieved an area under the ROC curve of 0.909 (95% CI 0.789–0.991) and an accuracy of 0.889 (95% CI 0.708–0.977). Conclusion: The molecular risk stratification based on TP53 mutation status combined with TMB level is strongly associated with DFS in MIBC. Radiomics signatures can effectively predict this stratification and provide valuable information to clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. Patient and methods: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. Results: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. Conclusion: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is ranked the ninth most common cancer in the world. Locally, the incidence of bladder cancer has increased tenfold over the past 26 years. Radical cystectomy (RC) is considered a gold standard management option for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has shown comparable oncological outcomes in selected patients. Materials and Methods: This is a retrospective study in which we reviewed medical records of patients diagnosed with MIBC without nodal disease or distant metastasis (cT2N0M0) who underwent either RC or TMT. Demographic data, comorbidities, histopathological and clinical staging, neoadjuvant/adjuvant therapy, and follow-up were analyzed. Results: We included a total of 31 patients in the study, with 10 patients in the TMT group and 21 patients in the RC group. There was no significant difference in recurrence between the TMT and RC groups (P = 0.58). The TMT group had a higher percentage of local recurrence (40% vs. RC 5.2%, P = 0.018) but no significant difference in metastasis (0% vs. 10%, P = 0.420). The difference in overall survival between the TMT and RC groups was not significant (P = 0.25). Conclusion: TMT may be considered an alternative option for patients unwilling to undergo RC due to related complications and prioritize a better quality of life. However, the decision should be made after considering the cost of extensive follow-ups and patient compliance with surveillance. [ABSTRACT FROM AUTHOR]

A 81-year-old male patient presented macroscopic hematuria. Flexible cystoscopy didn't give any diagnosis and urinary citology was negative. Total body CT showed a bladder inguinal hernia with diffuse thickening of the bladder wall, while abdomen bladder was regular.Diagnosis was difficult because flexible cystoscope could not reach the lesion, preventing diagnosis and bladder resection. We decided to reduce inguinal hernia surgically and perform a partial cystectomy removing the suspect neoplastic part of the bladder. Histologic examination showed muscle invasive squamous cell carcinoma with negative margins. After two years follow up, patient was free from bladder cancer, without any significative LUTS.

Objective: To evaluate long-term outcomes in patients homogenously treated with radical cystectomy and ileal conduit for muscle invasive bladder cancer. Method: The retrospective study was conducted at the Urology Department of Pakistan Kidney and Liver Institute and Research Centerm, Lahore, Pakistan, and comprised data from December 25, 2017, to January 16, 2023, related to patients who underwent radical cystectomy with ileal conduit with or without neo-adjuvant and adjuvant radiation, chemotherapy, or immunotherapy for papillary urothelial carcinom of the bladder. Clinical trajectory, histopathological characteristics and long-term clinical outcomes were noted. Data was analysed using SPSS 20. Results: In our study of 40 patients with muscle invasive bladder cancer, males predominated (32, 80%), with a median age of 57.4 years (IQR: 29-80). Diagnosis was early in 5 patients (12.5%) with varying hematuria durations, while 34 patients (85%) had a smoking history. Comorbidities included hypertension in 17 patients (42.5%), diabetes in 1 patient (2.5%), both hypertension and diabetes in 9 patients (22.5%), and a combination of hypertension, diabetes, and ischemic heart disease in 3 patients (7.5%). Transurethral resection was performed once in 13 patients (32.5%) and multiple times in 27 patients (67.5%). Additionally, 5 patients (12.5%) received immunotherapy, 11 patients (27.5%) underwent non-adjuvant radiation, and 14 patients (35%) received non-adjuvant chemotherapy. Papillary urothelial carcinoma was the predominant histological subtype among 37 (92.5%) patients. Patients receiving chemotherapy had significantly better overall survival (p=0.02).No significant differences were noted in recurrence or survival by therapy modality (p>0.05). These findings highlight the significance of early diagnosis, tailored treatments, and comorbidity management in muscle invasive bladder cancer patients. Age stratification revealed significant survival differences across groups (X² = 10.923, df = 3, p = 0.012). Analysis by complications did not show age-related survival variations (X² = 3.978, df = 3, p = 0.264). Conclusion: Achieving excellent long-term survival in MIBC patients requires a multidisciplinary approach, emphasizing early diagnosis, tailored treatment, and adherence to guidelines and protocols. Key Words: Radical cystectomy, Ileal conduit, Management, Muscle invasive bladder cancer, Papillary urothelial carcinoma.

Abstract Background Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. Methods To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. Results JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in “cancer-related pathways” and “EGFR-related signaling pathways”, which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively). Conclusions The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy. Graphical Abstract

Background: Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. Methods: To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. Results: JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in "cancer-related pathways" and "EGFR-related signaling pathways", which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively). Conclusions: The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract Muscle-invasive bladder cancers (MIBCs) is a group of molecularly heterogonous diseases that could be stratified into subtypes with distinct clinical courses and sensitivities to chemotherapy. Clinical application of molecular subtypes could help in prediction of neoadjuvant chemotherapy (NAC) responders. Immunohistochemical (IHC) markers such as GATA3, cytokeratin (CK) 5/6, and p53 are associated with these subtypes and are widely available. Human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) are mutated in multiple cancers including MIBC and are potential therapeutic targets. HER2/EGFR status of MIBC subtypes has not been investigated. Tissue microarrays (TMAs) were constructed from transurethral resection of the bladder tumor (TURB) specimens and stained with GATA3,CK5/6,p53 and HER2 in addition to Quantitative Reverse Transcription PCR for detection of EGFR gene. Of the total cases, 45% were luminal, 36.7% basal and 18.3% p53 wild subtype (p53-WT). Univariate analysis showed that overall survival (OS) and disease-free progression survival (DFS) were significantly longer for luminal subtype. In multivariate analysis, molecular subtype, HER2 status and LV invasion were independent prognostic factors for DFS and OS. Basal subtype showed a significantly better response to NAC. HER2 expression was significantly higher in luminal while EGFR expression was significantly higher in basal subtype. Kaplan-Meier survival curves revealed a significant longer OS and DFS for HER2 negative than positive cases. MIBC can be stratified using a simple IHC panel [GATA3,CK5/6,P53] into clinically relevant prognostic molecular subtypes. Basal tumors are aggressive and respond well to NAC while luminal have better OS. P53-WT tumors are chemoresistant and require further treatments. HER2 and EGFR are potential therapeutic targets for molecular subtypes of MIBC where luminal tumors are more likely to benefit from HER2 and basal from EGFR directed therapies.

Background: Bladder cancer is ranked the ninth most common cancer in the world. Locally, the incidence of bladder cancer has increased tenfold over the past 26 years. Radical cystectomy (RC) is considered a gold standard management option for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has shown comparable oncological outcomes in selected patients. Materials and Methods: This is a retrospective study in which we reviewed medical records of patients diagnosed with MIBC without nodal disease or distant metastasis (cT2N0M0) who underwent either RC or TMT. Demographic data, comorbidities, histopathological and clinical staging, neoadjuvant/adjuvant therapy, and follow-up were analyzed. Results: We included a total of 31 patients in the study, with 10 patients in the TMT group and 21 patients in the RC group. There was no significant difference in recurrence between the TMT and RC groups (P = 0.58). The TMT group had a higher percentage of local recurrence (40% vs. RC 5.2%, P = 0.018) but no significant difference in metastasis (0% vs. 10%, P = 0.420). The difference in overall survival between the TMT and RC groups was not significant (P = 0.25). Conclusion: TMT may be considered an alternative option for patients unwilling to undergo RC due to related complications and prioritize a better quality of life. However, the decision should be made after considering the cost of extensive follow-ups and patient compliance with surveillance.

Abstract Objective We aim to describe and highlight the current use of immune checkpoint inhibitors (ICIs) in the muscle invasive bladder cancer (MIBC) treatment landscape, particularly focusing on the perioperative setting. We provide a comprehensive review of key trials of the use of ICI in the perioperative setting, discussing trial outcomes and limitations and reviewing the role of biomarkers. Introduction ICIs have recently been integrated into the treatment algorithm for metastatic urothelial carcinoma. More than 30 published studies have investigated the role of these agents in the radical treatment of MIBC. Some studies have demonstrated conflicting results, affecting widespread adoption in clinical practice. Methods We performed a narrative overview of the literature from databases including PubMed, MEDLINE, Embase, European society of Medical Oncology/American Society of Clinical Oncology Annual Proceedings, and clinicaltrials.gov databases up until December 2021. Discussion We described the results of key trials in the neoadjuvant and adjuvant setting, some of the reasons for conflicting study results, and the implications for clinical practice. Relevant biomarkers in the field are discussed, alongside a brief overview of the immune microenvironment in bladder cancer. Conclusions Perioperative ICIs have shown promising efficacy with low toxicity in the neoadjuvant setting. The two large trials in the adjuvant setting have been contradictory. The efficacy of perioperative ICIs combined with favorable tolerability and better toxicity profile compared with chemotherapy, with the potential for biomarker-driven patient selection, may lead to a change in future practice. There is, however, a lack of long-term survival and toxicity data for those treated with ICIs, and this needs to be developed further to demonstrate an added survival benefit by using ICIs.

The presence of carcinoma in situ (CIS) is traditionally a contraindication to bladder-sparing approaches for muscle invasive bladder cancer (MIBC). Strategies that might aid in bladder preservation for this population require further investigation. We report a case of MIBC with CIS treated with both neoadjuvant systemic and intravesical chemotherapy prior to partial cystectomy.

Simple Summary: CD47 is a transmembrane protein expressed at a basal level in many cell types but is often overexpressed in tumor cells. CD47 overexpression has been correlated with adverse clinical outcomes in several malignancies. Hence, CD47 could be a promising candidate for target therapy in future cancer treatment. In this retrospective study of 87 patients with muscle invasion bladder cancer (MIBC), we examined CD47 IHC expressions in tumor samples from transurethral resections of bladder tumors (TURBT) and matched radical cystectomy (RC) specimens. We found detectable CD47 expressions in 44% of TURBT samples, but it was not a predictive or prognostic marker for MIBC patients. However, in patients receiving neoadjuvant chemotherapy (NAC), there was a positive trend toward decreased CD47 levels from TURBT to RC. The study suggests that further research is needed to understand the potential role of anti-CD47 therapy in MIBC patients and how NAC may modify immune surveillance mechanisms. Objective: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. Materials and Methods: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan–Meier method, respectively. Results: A total of 87 MIBC patients were included. The median age was 66 (39–84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2–14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. Conclusion: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC. [ABSTRACT FROM AUTHOR]

Nomogram prediction of overall survival that includes LODDS in carcinoma bladder. Retrospective cohort study of 282 cases from a tertiary care centre. The nomogram has superior predictive ability and higher clinical use than AJCC system. It will help clinicians for better patient counselling, planning follow-up strategies and designing clinical trials for newer adjuvant therapy (eg immunotherapy) in patients of MIBC. Background: To develop and validate a nomogram based on LODDS (Log ODDS of positive lymph-nodes) for prediction of overall survival (OS) in post radical cystectomy (RC) patients of muscle invasive bladder cancer (MIBC). Materials and Methods: Data was retrospectively collected from 282 cases of MIBC that underwent RC from 2011 to 2017 at our institute. Significant independent predictors were identified using Cox regression model and incorporated into a nomogram to predict 1, 2, and 4-year OS. Results: Multivariate analysis showed that Neo-Adjuvant Chemo-Therapy (NACT) (P < .001), LODDS (P < .001), T-stage (Pi = .001), CCI (Charlson Comorbidity Index) (P = .034) and grade (P = .003) were independent predictors of OS. The C-index of nomogram (0.740) was higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.614). The bias-corrected calibration plots showed that the predicted risks were in excellent accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram. Conclusion: A simple, easy to use nomogram to predict OS in cases of MIBC has been constructed. To best of our knowledge, LODDS has been incorporated for the first time. It has superior predictive ability and higher clinical use than AJCC system. It would help the clinicians for better patient counselling, planning follow-up strategies and designing a clinical trial for newer adjuvant therapy (eg immunotherapy) in post radical cystectomy patients of MIBC. [ABSTRACT FROM AUTHOR]

Objective: To cross-sectionally assess erectile and ejaculatory functions after tetramodal bladder-sparing therapy consisting of transurethral resection, chemoradiotherapy, and consolidative partial cystectomy in patients with muscle invasive bladder cancer. Materials and Methods: Among 72 enrolled male patients who underwent tetramodal bladder-sparing therapy from 2006 to 2019, 42 who visited the outpatient clinic from February to October 2020 received questionnaires. Erectile function, ejaculatory function, and quality of life were assessed using the International Index of Erectile Function short form, the Male Sexual Health Questionnaire Ejaculatory Dysfunction short form, and the Functional Assessment of Cancer Therapy. Results: Among the 42 patients, 9 were excluded because of incomplete responses and 33 were eligible for analyses. The median (range) age at survey and the time from treatment completion to responding to the questionnaires was 70 (50-87) years and 4.2 (0.4-14.0) years, respectively. The median International Index of Erectile Function short form-5 score was 11 (5-25), and 3 (9.1%) and 9 (27.3%) patients had no and mild erectile dysfunction, respectively. The Male Sexual Health Questionnaire Ejaculatory Dysfunction short form results showed that 23 (69.7%) patients responded that they could ejaculate. Patients with higher Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores had better erectile function and quality of life than those with lower Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores. Conclusion: Preservation of erectile and ejaculatory functions was demonstrated in muscle invasive bladder cancer patients treated with tetramodal bladder-sparing therapy. In addition to lower urinary tract function, preservation of male sexual function, especially ejaculatory function, in bladder-sparing therapy can be an advantage over radical cystectomy. [ABSTRACT FROM AUTHOR]

The current study aimed to report on the perioperative and long-term oncological outcomes of patients with muscle invasive bladder cancer who underwent radical cystectomy. Between January 2012 and December 2018, 207 patients were diagnosed with muscle invasive bladder cancer at our center, among whom 61 underwent radical cystectomy with a mean follow-up duration of 45.7 months. Postoperative complications were graded based on the Clavien–Dindo classification within 90 days after radical cystectomy. Disease-free survival and overall survival rates were determined according to tumor stage. Risk factors for perioperative complications, recurrence, and survival were assessed. The patients (n = 61) had a mean hospital stay of 20.9 days, with urinary diversion (23%), infection (18%), and blood transfusion (11.4%) being the most common complications following radical cystectomy. All complications were classified below Clavien–Dindo classification grade 3, most of which were controlled by conservative treatment. Re-operation within 90 days was required in 7 patients (11.5%) for enterolysis or cystorrhaphy, with no reported mortality after radical cystectomy. Carefully selected patients who underwent radical cystectomy, especially those with a Charlson Comorbidity Index of 0, 1, and 2 and clinical stage of T2 and T3, demonstrated better oncological outcomes compared to those who underwent trimodal therapy. The current study showed that adequately selected patients who underwent radical cystectomy had better oncological outcome compared to those who underwent trimodal therapy. The risk factors for perioperative complications included diabetes mellitus, male sex, smoking habit, alcohol consumption, and betel nut consumption. [ABSTRACT FROM AUTHOR]

Objective: We aim to describe and highlight the current use of immune checkpoint inhibitors (ICIs) in the muscle invasive bladder cancer (MIBC) treatment landscape, particularly focusing on the perioperative setting. We provide a comprehensive review of key trials of the use of ICI in the perioperative setting, discussing trial outcomes and limitations and reviewing the role of biomarkers. Introduction: ICIs have recently been integrated into the treatment algorithm for metastatic urothelial carcinoma. More than 30 published studies have investigated the role of these agents in the radical treatment of MIBC. Some studies have demonstrated conflicting results, affecting widespread adoption in clinical practice. Methods: We performed a narrative overview of the literature from databases including PubMed, MEDLINE, Embase, European society of Medical Oncology/American Society of Clinical Oncology Annual Proceedings, and clinicaltrials.gov databases up until December 2021. Discussion: We described the results of key trials in the neoadjuvant and adjuvant setting, some of the reasons for conflicting study results, and the implications for clinical practice. Relevant biomarkers in the field are discussed, alongside a brief overview of the immune microenvironment in bladder cancer. Conclusions: Perioperative ICIs have shown promising efficacy with low toxicity in the neoadjuvant setting. The two large trials in the adjuvant setting have been contradictory. The efficacy of perioperative ICIs combined with favorable tolerability and better toxicity profile compared with chemotherapy, with the potential for biomarker-driven patient selection, may lead to a change in future practice. There is, however, a lack of long-term survival and toxicity data for those treated with ICIs, and this needs to be developed further to demonstrate an added survival benefit by using ICIs. [ABSTRACT FROM AUTHOR]

Muscle-invasive bladder cancers (MIBCs) is a group of molecularly heterogonous diseases that could be stratified into subtypes with distinct clinical courses and sensitivities to chemotherapy. Clinical application of molecular subtypes could help in prediction of neoadjuvant chemotherapy (NAC) responders. Immunohistochemical (IHC) markers such as GATA3, cytokeratin (CK) 5/6, and p53 are associated with these subtypes and are widely available. Human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) are mutated in multiple cancers including MIBC and are potential therapeutic targets. HER2/EGFR status of MIBC subtypes has not been investigated. Tissue microarrays (TMAs) were constructed from transurethral resection of the bladder tumor (TURB) specimens and stained with GATA3,CK5/6,p53 and HER2 in addition to Quantitative Reverse Transcription PCR for detection of EGFR gene. Of the total cases, 45% were luminal, 36.7% basal and 18.3% p53 wild subtype (p53-WT). Univariate analysis showed that overall survival (OS) and disease-free progression survival (DFS) were significantly longer for luminal subtype. In multivariate analysis, molecular subtype, HER2 status and LV invasion were independent prognostic factors for DFS and OS. Basal subtype showed a significantly better response to NAC. HER2 expression was significantly higher in luminal while EGFR expression was significantly higher in basal subtype. Kaplan-Meier survival curves revealed a significant longer OS and DFS for HER2 negative than positive cases. MIBC can be stratified using a simple IHC panel [GATA3,CK5/6,P53] into clinically relevant prognostic molecular subtypes. Basal tumors are aggressive and respond well to NAC while luminal have better OS. P53-WT tumors are chemoresistant and require further treatments. HER2 and EGFR are potential therapeutic targets for molecular subtypes of MIBC where luminal tumors are more likely to benefit from HER2 and basal from EGFR directed therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer. We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following transurethral resection of bladder tumor. Of the 109 patients with inchworm sign, 94 (86.2%) were non-muscle invasive bladder cancer. Non-papillary tumors and tumors located in the bladder neck were significant predictors of muscle invasive bladder cancer with inchworm sign. Additionally, inchworm sign was not a prognostic factor in patients with non-muscle invasive bladder cancer in this study. Background: Inchworm sign is considered to be a characteristic finding in non-muscle invasive bladder cancer (NMIBC). Nevertheless, pathologically diagnosed muscle invasive bladder cancers (MIBCs) are occasionally diagnosed from tissue obtained by transurethral resection of bladder tumor (TURBT) in patients with inchworm sign. Methods: We retrospectively investigated the factors related to muscle invasive status in bladder cancer associated with inchworm sign and the role of inchworm sign in tumor outcomes following TURBT. Results: Of the 109 patients with inchworm sign, 94 (86.2%) and 15 (13.8%) were NMIBC and MIBC, respectively. Non-papillary tumors (hazard ratio (HR): 9.55, 95% confidence interval (CI): 2.07–44.10; p < 0.01) and tumors located in the bladder neck (HR: 7.73, 95% CI: 1.83–32.76; p < 0.01) were significant predictors of MIBC in bladder cancer with inchworm sign. Furthermore, recurrence-free survival (RFS) and progression-free survival were compared between patients with NMIBC with and without inchworm sign; however, no significant differences were found. In patients with NMIBC with inchworm sign, positive urine cytology was a prognostic factor for RFS (HR: 1.90, 95% CI: 1.04–3.48; p = 0.04). Conclusions: In bladder cancer with inchworm sign, 86.2% were NMIBC. Even in the case of inchworm sign, the presence of a non-papillary tumor or a bladder neck tumor before TURBT should be noted because of the possibility of MIBC. In this study, the inchworm sign was not a prognostic factor in patients with NMIBC. [ABSTRACT FROM AUTHOR]

Muscle Invasive Bladder Cancer (MIBC) is a subset of bladder cancer with a significant risk for metastases and death. It accounts for nearly 25% of bladder cancer diagnoses. A diagnostic work-up for MIBC is inclusive of urologic evaluation, radiographic imaging with a CT scan, urinalysis, and cystoscopy. These evaluations, especially cystoscopy, are invasive and carry the risk of secondary health concerns. Non-invasive diagnostics such as urine cytology are an attractive alternative currently being investigated to mitigate the requirement for cystoscopy. A pitfall in urine cytology is the lack of available options with high reliability, specificity, and sensitivity to malignant bladder cells. Exosomes are a novel biomarker source which could resolve some of the concerns with urine cytology, due to the high specificity as the surrogates of tumor cells. This review serves to define muscle invasive bladder cancer, current urine cytology methods, the role of exosomes in MIBC, and exosomes application as a diagnostic tool in MIBC. Urinary exosomes as the specific populations of extracellular vesicles could provide additional biomarkers with specificity and sensitivity to bladder malignancies, which are a consistent source of cellular information to direct clinicians for developing treatment strategies. Given its strong presence and differentiation ability between normal and cancerous cells, exosome-based urine cytology is highly promising in providing a perspective of a patient's bladder cancer. [ABSTRACT FROM AUTHOR]

Trimodal therapy (TMT) for muscle invasive bladder cancer has become an accepted alternative to radical cystectomy and has become integrated into national guidelines as standard a treatment option. The urologist plays a critical role in proper patient selection, thorough transurethral resection, ongoing cystoscopic surveillance and management of local recurrences. There exists multiple patient related and tumor related factors, which contribute to the selection of TMT vs. radical cystectomy for a patient with muscle invasive bladder cancer. Although the ideal patient for TMT has a tumor which can undergo a visibly complete resection, has no associated hydronephrosis, does not invade the prostatic urethra and is not associated with diffuse carcinoma in situ throughout the bladder, select patients who do not meet all these criteria can still be successfully treated with this approach. A multidisciplinary approach including urology, radiation oncology and medical oncology is paramount with clear communication of tumor location, timing of chemoradiation and repeat cystoscopic resection followed by surveillance. Nonmuscle invasive bladder cancer recurrences can occur in up to 26% of patients after completion of TMT, with many being treated by routine and standard therapy for non-muscle invasive bladder cancer. However, in this population after TMT, early salvage cystectomy should be considered in those with adverse features, including T1 disease, tumor greater than 3 cm, CIS, or lymphovascular invasion. Salvage cystectomy can be performed for local recurrences with acceptable oncologic control and no clear evidence of any greater risk of early complications; however, there may be a slightly increased risk for late complications, namely small bowel obstruction, ureteral stricture, and parastomal hernia. An understanding of these surgical considerations is of utmost importance to the treating urologist in selecting and managing a patient through TMT. [ABSTRACT FROM AUTHOR]

In localized muscle invasive bladder cancer (MIBC), the gold standard treatment is radical cystectomy (RC) with bilateral pelvic lymph node dissection (PLND), associated with cisplatin-based neoadjuvant chemotherapy, whereas first-line treatment for metastatic patients is cisplatin-based chemotherapy. In men with an abdominal aortic aneurysm (AAA), elective repair is recommended when its diameter is >5.5 cm, while cryopreserved arterial allografts (CAA) offer resistance to infection. A patient with simultaneous metastatic MIBC, associated with left hydronephrosis, and infrarenal AAA of 49 mm diameter was evaluated in an interdisciplinary study. Concomitant surgery was opted for; first, the AAA repair with CAA implantation was practiced, followed by retroperitoneal and common iliac lymphadenectomy. Thereafter, RC and PLND were conducted, and a Wallace-1 ileal conduit and a stoma were constructed. Chest and abdomen contrast-enhanced CT at 2 months showed the onset of two osteolytic lesions on the left ilium. At oncological re-evaluation the patient was deemed cisplatin-fit.

• The natural history of MIBC treated without curative intent is not well known. • Most patients (88%) were not treated due to low performance status. • 2-year cancer specific and overall survivals were 18% and 12%, respectively. • During follow-up 65% of patients suffered from recurrent hematuria. • About 59% of patients required catheter insertion and 37% had a nephrostomy tube. Muscle-invasive bladder cancer is an aggressive disease. Yet, many patients, especially those with advanced age and multiple comorbidities, do not receive treatment with curative intent. We evaluated the disease course and health care burden of these patients. Bi-center, retrospective analysis of patients diagnosed with muscle-invasive bladder cancer who did not undergo curative-intent treatment (radical cystectomy or trimodal therapy) between 2016 and 2021. Patient characteristics and treatment burden were described. Metastasis-free, cancer-specific, and overall survivals were evaluated using the Kaplan-Meier method. Sixty-six patients with a median age of 86 (IQR 78,90) were evaluated. The median follow-up for survivors was 29 months (IQR 9, 44). All patients were diagnosed with muscle-invasive bladder cancer, and 32 (48%) presented with clinical T3 and T4 disease. The median age adjusted Charlson comorbidity index at diagnosis was 7 (IQR 6,8). Treatment with curative intent was not provided due to comorbidities and low-performance status in 58 patients (88%) and patient refusal in 8 (12%). Two-year estimated metastasis-free survival, cancer-specific survival, and overall survival were 11%, 18%, and 12%, respectively. During follow-up, 7 patients (10%) were treated with chemotherapy, 4 (6%) received immunotherapy, 21 (32%) radiation, and 17 (26%) had emergent operations due to hematuria. Twenty-four patients (37%) required nephrostomy tubes, and 39 (59%) required an indwelling urinary catheter for various periods. Forty-three patients (65%) suffered from recurrent hematuria episodes. Overall, median emergency room visits were 4 (IQR 2, 6), and median hospital admission was 16 days (IQR 9, 29). Untreated muscle-invasive bladder cancer is associated with a limited lifespan and a high disease burden for the patient and health system. These data should be taken into consideration and portrayed to the patient when curative intent treatment is chosen to be avoided. [ABSTRACT FROM AUTHOR]

Objective To evaluate the predictive value of vesical imaging-reporting and data system (VI-RADS) based on multi-parameter magnetic resonance imaging (MRI) for muscle invasive bladder cancer. Methods Clinical data of 278 patients undergoing transurethral resection of bladder tumor (TURBT) or radical cystectomy in our hospital from January 2017 to March 2021 were collected in this study. After VI-RADS score was assessed by 2 radiologists independently, Kappa test was used for the consistency of the obtained scores. Chi-square test was employed to analyze the consistency of VI-RADS score with pathological results. Receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of VI-RADS scores in the diagnosis of muscle invasive bladder cancer. The consistency of VI-RADS score with pathological Results of tissues obtained by different surgical Methods was analyzed with Chi-square test. Results The VI-RADS scores of the 2 radiologists were consistent with each other (coincidence rate: 79.86%, kappa value: 0.750 8, P < 0.001). ROC curve analysis showed that the area under curve (AUC), Yodon index, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.774, 54.78%, 96.16%, 58.62%, 58.14% and 96.23%, respectively, when predicting muscular invasion with VI-RADS score ≥3 as the threshold. The study also found that the coincidence rate between the pathological Results of radical cystectomy and VI-RADS score was 92.85%, which was significantly higher than that of TURBT (79.81%, P < 0.05). Conclusion VI-RADS score based on preoperative multi-parameter MRI has good consistency and stability, and is highly consistent with the Results of postoperative pathology. VI-RADS score ≥3 has predictive diagnostic value for muscular-invasive bladder cancer and can guide the selection of clinical surgical methods.

Radical cystectomy plus pelvic lymph node dissection is the gold standard treatment for muscle invasive bladder cancer. However, the patients with severe medical complications cannot tolerate the operation, and the incidence rates of short- and long-term postoperative complications are quite high. In order to achieve good tumor control while preserve bladder function and maintain good quality of life, bladder preservation treatment is actively explored in China and at abroad. At present, triple or multiple combination therapy, including maximum transurethral bladder tumor resection, chemotherapy and external irradiation and radiotherapy, is mostly adopted. Studies have shown that its long-term tumor control effect is similar to that of cystectomy, and it has been recommended as an effective treatment option for muscle invasive bladder cancer by domestic and foreign specialized diagnosis and treatment guidelines. In the course of comprehensive treatment for bladder preservation, the efficacy of the treatment is currently evaluated by liquid biopsy, radiography, cystoscopic biopsy or surgical thoroughness of transurethral bladder tumor resection, and timely salvage radical resection can be performed for the patients with poor response. In addition, neoadjuvant chemotherapy may have no effect on the overall survival of the patients after bladder preservation combination therapy, but it can be used as a screening method for treatment response, and early radical surgery is recommended for patients with poor response. There is no standard treatment plan for bladder preservation combination therapy, and it is difficult to determine the best treatment population. Randomized controlled studies and long-term follow-up trial of the combination treatment in comparison with radical bladder resection need to be carried out. In view of the breakthrough efficacy of immune checkpoint inhibitors in the treatment of advanced uroepithelial carcinoma, the combination of immune checkpoint inhibitors and radiotherapy and chemotherapy may also be the direction of future research.