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Trimodal therapy consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy, has emerged as a valuable therapeutic alternative to radical cystectomy in patients with muscle invasive bladder cancer. Concomitant radiosensitising chemotherapy is a component of trimodality increasing locoregional control compared to radiotherapy alone. The combinations 5-fluorouracil with mitomycin or cisplatin are the best supported in the literature. Gemcitabine appears to be a feasible and promising alternative. There is considerable international heterogeneity in terms of dose, volumes and fractionation. The most commonly used regimens are moderately hypofractionated (55 Gy in 20 fractions over 4 weeks) and normofractionated (64 Gy in 32 fractions) regimens. Radiotherapy for bladder cancer is an effective and evolving treatment, with current technical developments, and studies of new combinations with systemic treatments underway. [ABSTRACT FROM AUTHOR]

Introduction: Incidence and mortality for bladder cancer has changed very little over the past 20 years. Approximately 40% of patients with high-risk nonmuscle invasive bladder cancer eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in bladder cancer. Our aim was to estimate and understand the direct costs associated with the treatment of bladder cancer from the payer's perspective in the USA, in the year of 2021, including costs for both newly diagnosed bladder cancer (stages 0a–IV) and recurrent patients. Methods: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data were based on the CancerMPact Patient Metrics (PM) database and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from medical literature and public data sources. Only direct costs were considered. Results: There were an estimated 83,532 newly diagnosed patients with bladder cancer of all stages in 2021 with a projected total cost of treatment of ~$2.6 billion. Average cost per newly diagnosed patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of ~$3.9 billion was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. Conclusions: Treatment and resource costs increase for bladder cancer as the disease recurs/progresses. More effective treatments that can delay recurrence/progression may reduce the economic burden associated with bladder cancer. Plain Language Summary: The costs of treating bladder cancer in the USA are high, expected to have exceeded $6.5 billion in the year 2021. The average cost for newly diagnosed patients ranges from $19,521 for the earliest stage of disease to $169,533 for metastatic disease. Average costs per patient increase upon disease recurrence and more effective initial treatments to delay disease recurrence or progression may reduce the costs associated with bladder cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: Bladder cancer (BC) is the most prevalent malignant tumor in the urinary tract, classified mainly into muscle-invasive BC (MIBC) and non-MIBC (NMIBC). Recent studies highlight the important role of changes in transcriptome activity in carcinogenesis, aiding in the identification of additional differentially regulated candidate genes, improving our understanding of the molecular basis of gene regulation in BC. This study aimed to evaluate the transcriptome of MIBC patients compared with normal subjects. Materials and Methods: mRNA sequencing was conducted using the Illumina NovaSeq 6000 Dx system in a case series comprising 11 subjects with MIBC and 19 healthy controls matched for age and sex. For functional analysis, the pathfindR package was utilized to comprehensively identify pathways enriched in omics data within active subnetworks. Results: Our results demonstrated the presence of differentiated pathways, including spliceosome activity, oxidative phosphorylation, and chemical carcinogenesis due to reactive oxygen species, in MIBC patients compared with controls. Conclusion: The identification of novel molecular pathways in MIBC patients could prove useful in defining cancer predisposition factors and exploring potential therapeutic options. [ABSTRACT FROM AUTHOR]

Introduction: To reduce the risk of disease recurrence and progression of intermediate and high-risk Non-Muscle Invasive Bladder Cancers (NMIBCs), intravesical adjuvant treatment with Bacillus Calmette-Guerin (BCG) represents the standard of care, although up to 50% of patients will eventually recur and up to 20% of them will progress to Muscle Invasive Bladder Cancer (MIBC). Radical Cystectomy (RC) is the treatment of choice in this setting; however, this represents a major and morbid surgery, thus meaning that not all NMIBCs patient could undergo or may refuse this procedure or may refuse. The search for effective bladder sparing strategies in NMIBCs BCG-unresponsive patients is a hot topic in the urologic field. Areas covered: We aimed to review the most important bladder-preserving strategies for BCG unresponsive disease, from those used in the past, even though rarely used nowadays (intravesical chemotherapy with single agents), to current available therapies (e.g. intravesical instillation with Gemcitabine-Docetaxel), and to future upcoming treatments (Oportuzumab Monatox). Expert opinion: At present, bladder-preserving treatments in BCG-unresponsive patients are represented by the use of intravesical instillations, systemic immunotherapies, both with good short-term and modest mid-term efficacy, and numerous clinical trials ongoing, with encouraging initial results, in which patients could be recruited. [ABSTRACT FROM AUTHOR]

Prostate and bladder cancer treatments have several challenges, including intense side effects and mechanisms of resistance. Thus, it is urgent to find drugs that can fill these gaps. For this purpose, Entecavir (ETV) was tested alone and in combination with 5-Fluorouracil (5-FU). Prior to this, a preliminary computational analysis was conducted to evaluate the combination of these two drugs. After exposing PC-3 and UM-UC-5 cells to the drugs, cell morphology was assessed using a microscope, while cell viability, proliferation, and cytotoxicity were evaluated using the MTT assay, and finally, the statistical analysis was performed. It was concluded that ETV showed significant cytotoxic effects in the PC-3 cells, and 5-FU, although not as effective as in other tumor types, it managed to inhibit the viability of the PC-3 cells. The combination of 5-FU with ETV after 72 h of exposure is an advantageous association, surpassing the results of each drug alone. In the UM-UC-5 cells, ETV alone did not produce the expected effect, neither did the combination. Nevertheless, repurposing ETV has proven to be an effective strategy in PC, especially through its combination with 5-FU. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) ranks as the tenth most common cancer globally. Histopathologically, BC is broadly categorized into urothelial and non-urothelial BC. Urothelial carcinoma represents over 90% of BC in most regions worldwide. The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer (NMIBC) is transurethral resection of bladder tumors (TURBT). Currently, the standard of care for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy. Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue. This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney, prostate gland, lung, liver, and breast, and is particularly effective for unresectable tumors, offering less trauma, quick recovery, good tolerability, and symptom control. However, cryoablation has its limitations. Over the past few years, cryoablation therapy has emerged as a new method for treating early BC. This treatment is minimally invasive, precise, and offers quick recovery, providing patients with a new treatment option. Although randomized studies are still limited, increasing evidence suggests its potential application in bladder cancer combined with transurethral resection (TURBT) or medication. Cryoablation is not standard therapy for bladder cancer. Treatment decisions should be discussed by a multidisciplinary team of urologists, oncologists, and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches. [ABSTRACT FROM AUTHOR]

This study assesses the impact of percutaneous nephrostomy (PCN) presence on standard intended neoadjuvant chemotherapy (NAC) quality, its related complications and outcome after radical cystectomy. We found that PCN-patients received less adequate NAC protocols, suffered from more infections and hospitalizations during the NAC period, with no difference in the postoperative outcomes after cystectomy. This finding may potentially lead to consideration of NAC avoidance and upfront cystectomy in PCN-patients. Introduction: Symptomatic hydronephrosis associated with muscle invasive bladder cancer (MIBC) necessitates percutaneous nephrostomy (PCN) insertion before neoadjuvant chemotherapy (NAC). This study assesses the impact of PCN presence on standard intended NAC quality, its related complications and outcome after radical cystectomy (RC). Materials and Methods: The study comprises a retrospective, multicenter cohort of 193 consecutive RCs performed between 2016 and 2019. Eighty (42%) of these patients received NAC and were divided in 2 comparison groups by presence (n = 26; 33%) or absence (n = 54; 67%) of PCN. Endpoints included completion of adequate NAC treatment (cisplatin-based chemotherapy for at least 4 courses), complications during NAC, post-RC complications and hospital stay. Results: Overall, patients with PCN (45/193; 23%) featured a higher referral rate to NAC (58% vs. 36%, P = .01), worse glomerular filtration rates (P < .001) and more adverse events (P = .04), in comparison to non-PCN patients. In the NAC cohort, PCN patients had less adequate treatment rates (54% vs. 85%, P = .005), and more infections (35% vs, 7%; P = .008) and hospitalizations (58% vs. 13%; P < .001) during chemotherapy. Post-RC outcome was similar for both comparison groups. PCN was an independent risk factor for inadequate NAC (OR = 3.9, P = .04), and infections (OR = 11.3, P = .01) and hospitalizations (OR = 7.5, P = .004) during NAC. Conclusions: PCN in MIBC patients is a significant risk factor for inadequate NAC and adverse events during treatment. This finding may quire the rationale of NAC, potentially leading to consideration of NAC avoidance and upfront RC in PCN patients. Further survival studies with long follow-up are needed for elucidating this issue. [ABSTRACT FROM AUTHOR]

While combined chemoradiotherapy is superior to radiotherapy alone bladder-preserving therapy in patients with bladder cancer, standard chemoradiotherapy regimens are prohibitively toxic for certain patients. We present results from our institutional experience treating patients with oral capecitabine concurrent with radiotherapy following transurethral resection of bladder tumor. Importantly, no patients required salvage cystectomy and overall toxicity was low. Introduction: Many patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. Materials and Methods: Patients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder + / ? pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. Results: Twenty-seven consecutive patients met cr iter ia for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3 + toxicities. Conclusion: Maximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity. [ABSTRACT FROM AUTHOR]

Bladder cancer is associated with a worse prognosis and a highly toxic treatment compromising patient's quality of life. As known, patients included in clinical trials benefit from strict inclusion criteria, more additional medical exams, and a very tight monitoring in comparison with patients treated with a recommended clinical practice. This retrospective study observed that an enrolment through clinical trial did not induce a significant impact on outcomes of bladder cancer patients receiving MVAC neoadjuvant chemotherapy. Introduction: MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) neoadjuvant chemotherapy a standard treatment for invasive bladder cancer is associated with mainly haematological toxicities. Randomized clinical trials remain a gold standard for treatment outcomes and efficacy assessment. Patients enrolled in clinical trials are selected and tend to benefit from a stricter follow-up unlike everyday clinical practice patients. Conversely, real-life observational studies better define the effectiveness of treatments in clinical routine practice. The aim of this study is to analyse the impact of clinical tr ial monitor ing on MVAC-related toxicities. Material and Methods: Patients with an infiltrative localized bladder cancer treated by MVAC neoadjuvant chemotherapy between 2013 and 2019 were enrolled, and divided into 2 groups: patients included in a clinical trial namely "VESPER study" during their treatment and patients treated in clinical routine practice. Results: Out of 59 patients were enrolled in this retrospective study, 13 patients were included in a clinical trial. Clinical characteristics were similar between the 2 groups. Comorbidities were more frequent in the nonclinical trial group (NCTG). Completed 6 cures treatment proportion was higher in the clinical trial group (CTG) (69.2% vs. 50%). Yet, in this group, patients had more doses reduction (38.5% vs. 19.6%). The proportion of complete pathologic response was higher in patients enrolled in clinical trial (53.8% vs. 39.1%). Statistically, the expected stricter monitoring due to clinical trial enrolment had no impact on the complete pathologic response and clinically relevant toxicities. Discussion: When compared to conventional clinical practice, clinical trial enrolment induced no significant difference on the pathologic complete response or toxicity rate. Further large prospective studies are needed to confirm these data. [ABSTRACT FROM AUTHOR]

We conducted systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy on survival and histopathological outcomes of variant histology of urothelial carcinoma of bladder. The present study found that bladder cancer patients with variant histology administration of neoadjuvant chemotherapy before surgery had better survival outcomes and higher pathologic down staging rate than those without administration of neoadjuvant chemotherapy before surgery. Purpose: To conduct systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy (NAC) on survival and histopathological outcomes of variant histology (VH) of urothelial carcinoma (UC) of bladder. Methods: This systematic review was registered in PROSPERO (CRD42023389115). Literature search was conducted in PubMed/Medline, Embase, and Cochrane Library for studies published up to January 2023. Population, intervention, comparator, outcome, and study design were as follows: bladder cancer patients with VH (population), neoadjuvant chemotherapy (intervention), radical cystectomy only (comparators), oncological survival and pathologic response (outcomes), and retrospective or prospective (study design). Results: Finally, a total of 17 studies were included in the present study (quantitative analysis, n = 17; qualitative analysis, n = 12). Pooled HR was 0.49 (95% CI: 0.31-0.76; P = .002) for OS. Pooled HR was 0.61 (95% CI: 0.38-0.98; P = .04) for CSS. Pooled HR was 0.44 (95% CI: 0.21-0.93; P = .03) in PFS. Pooled OR was 6.61 (95% CI: 4.50-9.73; P < .00001) in complete pathologic response. Pooled OR was 9.59 (95% CI: 3.56-25.85; P < .00001) in any pathologic response. Evidence quality assessments for each 5 comparisons using the GRADE approach were that Certainty was moderate in 1, low in 1, and very low in 3. Conclusions: Administration of NAC before surgery in bladder cancer patients with VH might confer better survival outcomes and higher pathologic down staging rate than no administration of NAC before surgery. [ABSTRACT FROM AUTHOR]

Bladder cancer is the tenth most common cancer and is a significant burden on health care services worldwide, as it is one of the most costly cancers to treat per patient. This expense is due to the extensive treatment and follow-ups that occur with costly and invasive procedures. Improvement in both treatment options and the quality of life these interventions offer has not progressed at the rates of other cancers, and new alternatives are desperately needed to ease the burden. A more modern approach needs to be taken, with urinary biomarkers being a positive step in making treatments more patient-friendly, but there is still a long way to go to make these widely available and of a comparable standard to the current treatment options. New targets to hit the major signalling pathways that are upregulated in bladder cancer, such as the PI3K/AkT/mTOR pathway, are urgently needed, with only one drug approved so far, Erdafitinib. Immune checkpoint inhibitors also hold promise, with both PD-1 and CDLA-4 antibody therapies approved for use. They effectively block ligand/receptor binding to block the immune checkpoint used by tumour cells. Other avenues must be explored, including drug repurposing and novel biomarkers, which have revolutionised this area in other cancers. [ABSTRACT FROM AUTHOR]

The combination of intravesical gemcitabine (Gem) with docetaxel (Doce) or with mitomycin C (MMC) has been used in the primary setting as an alternative to Bacillus Calmette-Guerin (BCG) to treat high-risk (HR) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC), as well in the rescue setting for patients in whom BCG has failed. Efficacy and safety of Gem/Doce and Gem/MMC to treat NMIBC in BCG-naive and failure settings. In the BCG-naive setting, Gem/Doce was the primary alternative combination therapy reported, with a weighted mean of 12- and 24-month recurrence-free survival (RFS) of 79% and 77% for HR disease and 84% and 76% for IR disease, respectively. In the HR BCG-failure setting, the weighted mean of 12- and 24-month RFS was 60% and 42% for Gem/Doce and 63% and 40% for Gem/MMC. While patients without BCG exposure and papillary disease only benefit the most from Gem/Doce, there is also reasonable efficacy in BCG refractory disease and CIS. Combination therapy is well tolerated, with grade III toxicity reported in less than 1% of patients. Unlike single-agent chemotherapy, intravesical Gem/Doce is considered effective and safe regardless of risk-stratification. [ABSTRACT FROM AUTHOR]

Introduction: Autophagy is an intracellular process that plays a key role in the cellular homeostasis. Recently, it has been described as a potential therapeutic target in oncology, whether by activating or inhibiting its different cascades. Autophagy inhibitors interact with different molecular processes of the hallmarks of cancer. Areas covered: Multiple proteins of the autophagy cascade could be aimed by specific inhibitors in many tumors, notably bladder cancer. In fact, bladder cancer has been increasing in prevalence over the last decade, and resistance to conventional treatment has been extensively reported in the literature. Autophagy inhibitors in bladder cancer have been described in preclinical studies to increase the sensitivity of the tumor to chemotherapy and radiotherapy. This paper is a review of the literature, which selected randomized trials, cohort studies, and case--control studies documenting the relationship between autophagy inhibitors and bladder cancer treatment. Expert opinion: Autophagy is a promising pathway for cancer cell targeting that opens the horizons for a potential new therapeutic area in particular the multidisciplinary management of bladder cancer. [ABSTRACT FROM AUTHOR]

Background/Aim: IgG4-related disease (IgG4RD) is a rare autoimmune proinflammatory condition that mimics other cancers and has unique pathological findings. The effects of radiotherapy in patients with IgG4RD remain unknown. Case Report: A male patient in his seventies who received radiotherapy (68 Gy/39 fr) for bladder cancer 5 months prior, presented to our hospital with fatigue and swelling in both legs. The patient had a history of IgG4- related sclerosing cholangitis, a subtype of IgG4RD. Leg edema gradually worsened despite treatment with a diuretic agent. Computed tomography showed hyperdense soft-tissue lesions in the irradiated area. The serum level of IgG4 increased to 1,380 mg/dl. One month after administration of a corticosteroid (10 mg per day) as an ex juvantibus treatment for IgG4RD, leg edema disappeared. Soft-tissue lesions in the irradiated area decreased in size. The adverse event was ultimately diagnosed as the recurrence of IgG4RD in the irradiated area. To the best of our knowledge, this is the first case report of an adverse event of radiotherapy for a patient with IgG4RD. Conclusion: We experienced a unique adverse event of radiotherapy in a patient with IgG4RD. Caution is advised on radiotherapy administration in patients with IgG4RD. [ABSTRACT FROM AUTHOR]

Treatment of recurrent low-volume low-risk NMIBC include: TURBT, office fulguration and active surveillance. The clinical significance of post-office fulguration single dose mitomycin C instillation is unknown. In a single-institution retrospective cohort of 108 patients, we found that single-dose post-office fulguration MMC was associated with longer recurrence-free-survival (median RFS 20 months 95% CI 4-36) compared to the controlled group that did not receive adjuvant mitomycin C instillation (median RFS 9 months 95% CI 5-13) (P = .038). The treatment was safe and well-tolerated. Prospective evaluation is warranted. Introduction: Perioperative instillation of mitomycin-C (MMC) has shown effectiveness in reducing the recurrence of low-grade non-muscle invasive bladder cancer (NMIBC). Data is lacking about the impact of single-dose MMC following office fulguration of low-grade urothelial carcinoma. We compared the outcomes of small-volume low-grade recurrent NMIBC in patients treated with office-fulguration - with and without an immediate single-dose instillation of MMC. Patients and Methods: A retrospective analysis of medical records of patients with recurrent small-volume (=1 cm) low-grade papillary urothelial cancer who underwent fulguration in a single institution between January 2017 and April 2021 either with or without instillation of post-fulguration MMC (40mg/50 mL). The primary outcome was recurrence-free survival (RFS). Results: Of 108 patients (27% women) who underwent fulguration, 41% received intravesical MMC. The treatment and control groups had similar sex ratio, mean age, mass size, tumor multifocality and or tumor grade. Median RFS was 20 months (95% CI 4-36) in the MMC group and 9 months (95% CI 5-13) in the control group (P = .038). Multivariate Cox regression analysis showed that MMC instillation was associated with longer RFS (OR = 0.552, 95% CI 0.320-0.955, P = .034) and multifocality was associated with shorter RFS (OR = 1.866, 1.078-3.229, P = .026). A higher rate of grade 1-2 adverse events was observed in the MMC group (18.2%) vs. the control (6.8%, P = .048). No complications grade 3 or higher were observed. Conclusion: A single dose of MMC instilled after office fulguration is associated with longer RFS compared to patients who did not receive MMC after the procedure, with no associated high-grade complications. [ABSTRACT FROM AUTHOR]

In this study of 229 locally advanced bladder cancer patients, upfront radical cystectomy seemed a viable option in those patients not fit to receive neoadjuvant chemotherapy due to malignant obstructive uropathy and other medical causes. Moreover, surgical resection improved the opportunity to receive perioperative systemic therapy by more than 50% and without compromising the oncological outcomes. Aim: Optimal utilization of perioperative systemic therapy in locally advanced bladder cancer (LABC) holds the key in improving the survival outcomes. We aim to analyze the oncological outcomes of clinically locally advanced urothelial bladder cancer patients treated with neoadjuvant (NACT) or adjuvant chemotherapy or without any systemic therapy in the per ioperative per iod of radical cystectomy. Methods & Material: We retrospectively analyzed the medical records of patients with cancer of the urinary bladder diagnosed between 2012 and 2020. The demographic profile, and the treatment received, was recorded for all patients. Oncological outcomes of the patients based on these variables were analyzed. Results: Two hundred and twenty nine (229) locally advanced bladder cancer patients were included in the study. Eighty eight (38%) of them underwent upfront radical cystectomy and 141 (62%) received neoadjuvant chemotherapy (NACT). With a median follow-up of 27 months, the 2-year DFS in either of the groups was 65.4% and 67.1% respectively (P - 0.373). In the multivariate analysis, the pathological lymph nodal status and lymph vascular invasion (LVI) status influenced the DFS. The initial modality of management chosen did not affect the outcome. (HR -- 0.688; 95% CI: 0.38-1.21). The commonest reason for not receiving NACT was Cisplatin ineligibility due to malignant obstructive uropathy and a subgroup analysis of this set of patients also did not show any significant difference in 2 year DFS compared to those who received NACT. Conclusion: A significant proportion of patients with LABC are unable to receive the recommended neoadjuvant chemotherapy and obstructive uropathy is the commonest reason for this in our centre. In our single centre series upfront radical cystectomy followed by adjuvant platinum based therapy had an outcome similar to neoadjuvant chemotherapy in LABC patients, in patients who were unable to receive the same due to various reasons. [ABSTRACT FROM AUTHOR]

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer. [ABSTRACT FROM AUTHOR]

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INTRODUCTION: Cluster of differentiation 44 (CD44), a transmembrane glycoprotein and Matrix metalloproteinase 2 (MMP2), a gelatinase enzyme have been implicated in several malignancies for their role in prognostication and diagnosis. We, therefore, made an effort to use these markers in urothelial malignancies and discuss their importance along with review of the literature. METHODS: A prospective study conducted for 1 year using light microscopy and immunohistochemistry for CD44 and MMP2. RESULTS: CD44 showed concordance with low-grade tumors while MMP 2 was found to show positivity in high-grade tumors. Score 3 in CD44 expression was seen exclusively (100%) in low-grade tumors while similar score of MMP2 expression was seen in 90.9% of high-grade tumors. CONCLUSION: CD44 and MMP2 expression can, therefore, serve as an important tool to predict the clinical behavior and prognosis in patients of urothelial carcinoma of the bladder. The management and survival rate varies according to grade; hence, these markers can be used for prognostication of disease. [ABSTRACT FROM AUTHOR]

Introduction. We aimed to compare the survival results of patients with muscle-invasive bladder cancer who responded after neoadjuvant chemotherapy (NAC) and did not accept further treatment and those who underwent radical cystectomy or received chemoradiotherapy (CRT). Material and methods. The study included 53 patients with non-metastatic muscle-invasive bladder cancer who received NAC between 2009 and 2020. Clinical findings and post-NAC survival analysis were evaluated. Survival analyses of patients who underwent radical cystectomy (RC) after NAC, received CRT, and refused treatment were compared. Results. The median age at diagnosis was 61 (33-80) years. After NAC, 18 patients (34%) received CRT, 9 patients (17%) underwent RC, and 18 patients (34%) refused further treatment. Complete response (CR) was present in 10 (18.4%) patients, partial response (PR) in 35 (66%) patients, stable disease (SD) in 1 (1.9%) patient, and progression in 7 (13.2%) patients. Median overall survival (OS) was 78 months. Median OS was not reached in the RC arm; it was 97 months in the CRT arm and 78 months in the declined-treatment arm. There was no statistical difference between the arms (p = 0.94). Median disease-free survival (DFS) was 32 months. Median DFS in the RC arm was 30 months, in the CRT arm -- 34 months, and 28 months in the declined-treatment arm after NAC. There was no statistically significant difference between the arms (p = 0.74). Conclusions. We did not find any difference in terms of OS and DFS between patients who after NAC underwent RC, CRT, or refused treatment. [ABSTRACT FROM AUTHOR]

Validated biomarkers to predict response to preoperative chemotherapy in bladder cancer are lacking. We investigated the predictive/prognostic impact of the pretreatment NLR in 404 bladder cancer patients treated with preoperative chemotherapy and radical surgery. A high NLR was associated with a decreased probability of complete and/or partial response to chemotherapy. NLR may risk-stratify patients prior to radical surgery. Introduction: There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC). Patients and Methods: We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). Results: A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model. Conclusion: We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation. [ABSTRACT FROM AUTHOR]

Studies about perioperative complications and all-cause mortality in frail patients requiring radical cystectomy (RC) are scarce. In this retrospective cohort study we identified individuals underwent RC (95 frail and 89 nonfrail). RC in frail patients was associated with increased mortality and morbidity but it remains a feasible option. Background: Studies about perioperative complications and all-cause mortality in frail patients requiring radical cystectomy (RC) are scarce. We aimed to assess the short- and long-term effect of RC in frail patients with bladder cancer. Patients and Methods: We performed a retrospective, cohort study including patients who underwent open RC due to bladder cancer from November 2013 to June 2022. Patients were considered frail when they fulfilled one of the following cr iter ia: i) age = 75 years; ii) Charlson Comorbidity Index = 9; iii) American Society of Anesthesiologists classification = 4; or iv) Clinical Frailty Scale score = 5. We evaluated all-cause mortality and complications in frail versus nonfrail patients. The effect of urinary diversion with ileal conduit versus ureterocutaneostomy in frail patients was also assessed via a Cox regression analysis. Results: Overall, 184 individuals underwent RC (95 frail and 89 nonfrail). A total of 130 patients (80%) presented at least one perioperative complication. This proportion was even higher among frail patients (86%). Similarly, severe perioperative complications were more common in frail patients based on the Clavien-Dindo classification (P = 0.044). Regarding disease progression and long-term complications, no statistically significant differences were observed between frail and nonfrail patients. The survival analysis with Kaplan-Meier curves demonstrated that the risk of death was increased in frail patients (log-rank test = 0.027). Based on the multivariate Cox regression analysis adjusting for major risk factors, urinary diversion with ureterocutaneostomy was significantly associated with increased mortality in frail patients compared to ileal conduit (Hazard Ratio: 3.5, 95% Confidence Interval: 1.3-9.4, P = 0.01). Conclusions: RC is feasible in frail patients but is associated with increased perioperative morbidity and mortality. Preoperative frailty screening should be implemented to counsel and carefully select patients eligible for RC. [ABSTRACT FROM AUTHOR]

We evaluated the use of BCG and Mitomicin C instillations administered with Electromotive Drug Administration (EMDA) in patients with nonmuscle invasive bladder cancer in whom Bacillus Calmette-Guerin (BCG) therapy had failed, in order to provide bladder preservation for these patients. We evaluated the oncological outcomes and tolerability in a long follow up This treatment seems to be safe and to provide good responses in well selected patients, without a high progression rate. Background: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed.Objectives: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. Material and Methods: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. Results: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. Conclusion: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases. [ABSTRACT FROM AUTHOR]

We evaluated log odds of positive lymph nodes (LODDS) as a prognostic marker in patients who underwent radical cystectomy with lymph node dissection. We found that LODDS is an independent predictor of overall survival and is superior to other measures of lymph node burden including lymph node ratio and conventional node staging. Background: Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscleinvasive bladder cancer (MIBC) and high r isk non-MIBC. The Amer ican Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. Patients and methods: Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. Results: Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P -value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P = .009). Conclusions: Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC. [ABSTRACT FROM AUTHOR]

To explore if texture analysis of Muscle Invasive Bladder Cancer (MIBC) can aid in better patient selection for bladder preservation. There was a significant difference in the mean of the pixels between the recurrence and the no recurrence group. Texture analysis can aid in better patient selection for bladder preservation. Purpose: To explore if texture analysis of Muscle Invasive Bladder Cancer (MIBC) can aid in better patient selection for bladder preservation. Methods: Pretreatment noncontrast CT images of 41 patients of MIBC treated with bladder preservation were included. The visible tumor was contoured on all slices by a single obser ver. The primar y endpoint was to identify texture parameters associated with disease recurrence posttreatment. The secondary endpoints included intra and interobserver variability, single and multislice analysis, and differentiating the texture features of normal bladder and tumor. For interobserver variability of bladder tumor texture features, 3 observers contoured the visible tumor on all slices independently. Observer 1 contoured again at an interval of 1 month for intraobserver variability. Results: The median follow-up was 30 months with 12 patients having a recurrence. In the primary endpoint analysis, the mean of the pixels at Spatial Scaling Filter (SSF) 2 for the no recurrence group and recurrence group was 6.44 v 13.73 respectively (P = .031) and the same at SSF-3 was 11.95 and 22.32 respectively (P = .034). The texture features that could significantly differentiate tumor and normal bladder were mean, standard deviation and kurtosis of the pixels at SSF-2 and entropy and kurtosis of the pixels at SSF-3. Overall, there was an excellent intra and interobserver concordance in texture features. Only multislice analysis and not single-slice could differentiate recurrence and no recurrence posttreatment. Conclusions: Texture analysis can be explored as a modality for patient selection for bladder preservation along with the established clinical parameters to improve outcomes. [ABSTRACT FROM AUTHOR]

To identify risk factors for upper urinary tract recurrence (UUTR) in patients treated with radical cystectomy (RC) for urothelial bladder carcinoma (UBC). The PubMed, Web of Science, and Cochrane Library were searched on March 2022 to identify relevant studies according to the Preferred Reporting Items for Systematic Review (PRISMA) statement. We included studies that provided multivariate logistic regression analyses. The pooled UUTR rate was calculated using a fixed effect model. We identified 235 papers, of which seven and 6 articles, comprising a total of 8981 and 8404 UBC patients, were selected for qualitative and quantitative analyses, respectively. Overall, 418 (4.65%) patients were diagnosed with UUTR within a median time of 1.4 to 3.1 years after RC. Risk factors for UUTR were surgical margin (hazard ratio [HR] 3.41, 95% confidence interval [CI] 2.59-4.49, P < .00001), preoperative hydronephrosis (HR: 1.74, 95% CI: 1.25-2.43, P = .001), ureteral margin (HR: 4.34, 95% CI: 2.75-6.85, P < .00001), and pT stage (HR: 2.69, 95% CI: 1.37-5.27, P < .004). Incorporation of established risk factors into a clinical prediction model might aid in the decision-making process regarding the intensit y and t ype of surveillance protocols after RC as well as help determine the pretest probability of UUTR. [ABSTRACT FROM AUTHOR]

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Platinum-based NAC followed by cystectomy is standard of care for MIBC, however improvement of response rates is needed. In this phase I/II trial, neoadjuvant gemcitabine-cisplatin-rapamycin combination was used to suppress response to platinum-derived DNA damage by the tumor microenvironment. Although rapamycin successfully suppressed damage response, treatment efficacy did not improve, suggesting the existence of alternative platinum resistance pathways. Introduction: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscleinvasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade. Patients & Methods: We conducted a phase I/II clinical trial to assess the safety and efficacy of gemcitabine-cisplatin-rapamycin combination. Grapefruit juice was administered to enhance rapamycin pharmacokinetics by inhibiting intestinal enzymatic degradation. Phase I was a dose determination/safety study followed by a single arm Phase II study of NAC prior to radical cystectomy evaluating pathologic response with a 26% pCR rate target. Results: In phase I, 6 patients enrolled, and the phase 2 dose of 35 mg rapamycin established. Fifteen patients enrolled in phase II; 13 were evaluable. Rapamycin was tolerated without serious adverse events. At the preplanned analysis, the complete response rate (23%) did not meet the prespecified level for continuing and the study was stopped due to futility. With immunohistochemistry, successful suppression of the mTOR signaling pathway in the tumor was achieved while limited mTOR activity was seen in the TME. Conclusion: Adding rapamycin to gemcitabine-cisplatin therapy for patients with MIBC was well tolerated but failed to improve therapeutic efficacy despite evidence of mTOR blockade in tumor cells. Further efforts to understand the role of the tumor microenvironment in chemotherapy resistance is needed. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to determine whether sarcopenia is a predictor of overall survival (OS) and cancer-specific survival (CSS) in patients with bladder cancer (BC) undergoing radical cystectomy (RC). Material and methods Patients who underwent radical cystectomy for BC between September 2016 and June 2022 were retrospectively reviewed. Patients underwent digital computed tomography (CT) scans of the abdomen and pelvis. The skeletal muscle index (SMI) was used to assess sarcopenia using CT images. OS and CSS were estimated using Kaplan-Meier curves. Predictors of CSS and OS were analysed using univariate and multivariate Cox regression models. Results Of the 84 reviewed patients, 45 (53.6%) had sarcopenia. The median follow-up period for survivors was 70 months. Patients with sarcopenia were older and had a lower BMI, but other preoperative clinical and laboratory parameters were similar to those of patients without sarcopenia. During follow-up, 57 (67.9%) patients died, 39 (46.4%) due to BC. In addition, patients with sarcopenia had worse 5-year OS (24.4% vs 41.0%, p = 0.036) and CSS (35.6% vs 61.5%, p = 0.012) than non-sarcopenic patients. The findings indicate that sarcopenia is an independent predictor of increased CSS (HR, 2.841; p = 0.003) and overall mortality (HR, 2.465; p = 0.004) in multivariate analysis. Conclusions The results of this study support the view that sarcopenia is an important risk factor for predicting CSS and OS in BC patients undergoing RC. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Muscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this population in randomized controlled trials of AC. We sought to define survival benefits in this patient population through our institutional bladder cancer database. Methods: Retrospective review of all patients undergoing radical cystectomy for urothelial carcinoma of the bladder from 2004–2020 with ≥pT3b disease irrespective of neoadjuvant chemotherapy (NAC) use was conducted. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using the Kaplan-Meier method with log-rank test, and the Cox-proportional hazards model was used to identify predictors of improved PFS and OS. AC was defined by any chemotherapy use within 90 days of cystectomy, regardless of STSM status. Results: 476 patients with pT3b disease or worse were identified. Median follow-up was 12.3 months. An amount of 21% of patients were treated with AC. An amount of 24% of patients had positive STSM. Median OS for patients with positive STSM was 8.4 months [95% CI 7–11.5] and 18.3 months [95% CI 15.6–20.8] (p < 0.001) for patients with negative STSM. In the overall cohort, positive STSM (HR 1.93, 95% CI 1.45–2.57, p < 0.001), AC use (HR 0.68, 95% CI 0.51–0.90, p = 0.007), and pN1–3 disease (HR 1.47, 95% CI 1.16–1.87, p = 0.002) were independent predictors of OS when adjusted for performance status, pT-stage, and neoadjuvant chemotherapy use. In patients with positive STSM, median survival was seven months [95% CI 5.2–8.4] without AC, compared to 16.2 months [95% CI 11.5–52.5] with AC (p = 0.0038). For patients with negative STSM, median survival was 17.4 months [95% CI 14–20.1] without AC compared to 22.3 months [95% CI 17.2–36.9] with AC (p = 0.23). In patients with positive STSM, AC use was the only factor associated with an OS benefit with a HR of 0.41 (95% CI 0.21–0.78, p = 0.007). In patients with negative STSM, pT4 and pN1–3 disease were the only factors associated with worse overall survival with a HR of 1.32 (95% CI 1.00–1.74, p = 0.050) and 1.97 (95% CI 1.49–2.60, p < 0.001), respectively. Conclusions: Administration of adjuvant chemotherapy is of particular benefit in patients with positive STSM following radical cystectomy for gross extravesical disease. Positive STSM may be a representative of "early metastatic" or micrometastatic disease. [ABSTRACT FROM AUTHOR]

Bladder cancer is the tenth most common cancer and is a significant burden on health care services worldwide, as it is one of the most costly cancers to treat per patient. This expense is due to the extensive treatment and follow-ups that occur with costly and invasive procedures. Improvement in both treatment options and the quality of life these interventions offer has not progressed at the rates of other cancers, and new alternatives are desperately needed to ease the burden. A more modern approach needs to be taken, with urinary biomarkers being a positive step in making treatments more patient-friendly, but there is still a long way to go to make these widely available and of a comparable standard to the current treatment options. New targets to hit the major signalling pathways that are upregulated in bladder cancer, such as the PI3K/AkT/mTOR pathway, are urgently needed, with only one drug approved so far, Erdafitinib. Immune checkpoint inhibitors also hold promise, with both PD-1 and CDLA-4 antibody therapies approved for use. They effectively block ligand/receptor binding to block the immune checkpoint used by tumour cells. Other avenues must be explored, including drug repurposing and novel biomarkers, which have revolutionised this area in other cancers.

The article discusses the results of a survey conducted among urologists who contribute to the Central European Journal of Urology (CEJU) regarding methods used in their centers to shorten the waiting time for patients suspected of having bladder cancer. The survey found that there are no consistent systemic solutions to expedite the transition to subsequent stages of the procedure in most countries. However, some centers have implemented fast-track systems for managing suspected neoplasms. The article emphasizes the importance of effective procedures and organization in reducing delays and improving outcomes for bladder cancer treatment. [Extracted from the article]

Data from a consecutive series of 2395 patients with primitive or progression to muscle invasive bladder cancer (MIBC) undergoing to radical cystectomy and lymph nodes dissection in 5 centers were evaluated. A quick nomogram to predict death from cancer and relapse was developed. The nomogram showed to be effective and accurate in predicting both outcomes. The nomogram may improve communication with the patients. Objectives: To develop an easy tool to predict cancer specific (CSS) and disease-free survival (DFS) in patients with bladder cancer treated with radical cystectomy. Methods: Data from a consecutive series of 2395 patients with primitive or progression to muscle invasive bladder cancer (MIBC) undergone to radical cystectomy and lymph nodes dissection in 5 centers were evaluated. Using Cox proportional hazards analyses, the Cancer of the bladder risk assessment (CRAB) nomogram was generated. Accuracy of the nomogram was evaluated by Harrell's C test. Internal validation of the model was performed using 200 bootstraps. Results: Median age was 66 (IQR 58/73) years; 612/2395 (26%) patients presented an advanced pathological stage (=pT3a); 478/2395 (20%) presented positive lymph nodes. Overall, 729/2395 (30%) presented local or distant recurrence with a median DFS of 42 (IQR 14/89) months. Overall, 642/2395 (27%) died of bladder cancer with a median follow up of 48 (IQR 22/92) months. On univariate Cox proportional hazards analyses, age, stage, and lymph nodes density were a significant predictor of 3 and5 years CSS and DFS. Accuracy of the CRAB nomogram was 0.73 and 0.71 respectively. Conclusion: CRAB nomogram can be a practical and easily applicable tool that may help urologists to classify the long-term CSS and DFS of patients treated with radical cystectomy and to predict the oncological outcome. [ABSTRACT FROM AUTHOR]

Radical cystectomy is the popular therapy for muscle-invasive bladder cancer. Concurrent chemoradiation is an accepted alternative. In his single-arm clinical trial, we sought the outcomes of patients treated with chemoradiotherapy using once daily radiation and concurrent cisplatin and capecitabine. Considering the promising response and compliance rates, the administration of our protocol warrants further attention in the context of MIBC treatment. Purpose : To evaluate the feasibility, tolerance and efficacy of cisplatin + capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC). Methods : MIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m 2) and capecitabine (625 mg/m 2 ). The primary endpoint was treatment tolerability, defined as receiving capecitabine + cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates. Results : This study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade = 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomyfree survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87). Conclusion : The promising tolerability rate seen with concurrent cisplatin + capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC. [ABSTRACT FROM AUTHOR]

Background: Since tobacco smoking represents the most established risk factor for bladder cancer, we sought to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence and to contrast it with lung cancer. Methods: The annual overall tobacco smoking prevalence rates were extracted from the Report of the Surgeon General and the Center for Disease Control between 1953 and 1983. The overall age-adjusted incidence rates for bladder and lung cancers were derived from the Surveillance, Epidemiology, and End Results database between 1983 and 2013 (30-year latency period). Weighted least square regression models were used to assess bladder and lung cancer incidence rate differences (IRD) related to trends in tobacco smoking prevalence. A Wald test was used to compare whether the prevalence of tobacco smoking, as an explanatory variable, differentially predicts bladder versus lung cancer incidence rates. Results: The associations between tobacco smoking prevalence and bladder cancer incidence were not significant in the overall (IRD = +0.04; 95%CI (−0.14; +0.22); p = 0.63), male (IRD = +0.07; 95%CI (−0.09; +0.23); p = 0.37), or female (IRD = +0.12; 95%CI (−0.01; +0.25); p = 0.06) populations. There was an association between tobacco smoking prevalence and lung cancer incidence in the overall (IRD: +3.55; 95%CI (+3.09; +4.00); p < 0.001), male (IRD: +4.82; 95%CI (+4.44; +5.20); p < 0.001), and female (IRD: +3.55; 95%CI (+3.12; +3.99); p < 0.001) populations. The difference between the observed associations of tobacco smoking prevalence with bladder versus lung cancer incidence was also significant in all examined populations (p < 0.001). Conclusions: Variations in tobacco smoking prevalence only partially explained the trends in the incidence of bladder cancer, indicating that its etiology is complex. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to evaluate the clinical safety and efficacy of super-selective transcatheter vesical arterial chemoembolization with epirubicin-loaded CalliSpheres® beads (DEB-TACE) for treating muscle-invasive bladder cancer with hematuria. Methods: We reviewed the retrospective records of 20 muscle-invasive bladder cancer patients with hematuria who were treated with super-selective transcatheter vesical arterial by oxaliplatin and 100–300-μm CalliSpheres loaded with epirubicin. The primary outcomes were the technical and clinical success rates. The secondary outcomes were complications, treatment responses, quality of life (QOL), median overall survival, and 1- and 2-year survival rates. QOL was routinely assessed by nurses at admission and during telephone follow-up 4 weeks after discharge. Results: The technical success rate was 80.0% (16/20). Bleeding was controlled after the first embolization in 18/20 patients and after re-embolization within 7 days of the first embolization in the remaining two patients. The clinical success rate was 90% (18/20). After 4 weeks of follow-up, the mean hematocrit and hemoglobin levels improved significantly (P < 0.05). Four patients (20.0%) showed hematuria recurrence during a 4–8-month follow-up period. There were no severe complications, such as necrosis of the bladder, genitals, perineal skin, or procedure-related deaths. The complete response, partial response, stable disease, and progressive disease frequencies were 5.0%, 55.0%, 25.0%, and 15.0%, respectively, resulting in an objective response rate of 60.0% and a disease control rate of 85.0% after 1 month. 4 weeks after embolization, QOL was significantly higher than that pre-operation, except for social/family status (P < 0.05). The median overall survival was 18.5 months, and the 1- and 2-year survival rates were 75.0% and 46.7%, respectively. Conclusion: DEB-TACE is safe and effective for treating muscle-invasive bladder cancer with hematuria, preserving bladder function and improving the QOL. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is the ninth and 4 most prevalent cancer in men worldwide and in the United States. Urothelial carcinoma (UC) is the most common histological kind. Biosensors are devices that translate complex biological events into an electrical signal whose intensity is proportional to the analyte's concentration, allowing them to detect a specific biological analyte. The nanotechnology with nanoparticles improves and modifies the biorecognition element to improve the biosensing phenomenon, making it one of the most popular subjects among scientists. Employment of ZincOxide (ZnO) nanoparticles into the polyacrylamide (PAM) is supposed to enhance electrical and sensory capabilities that promise more inventive and faster detection with improved repeatability. Studying the ability of PAM\ZnO nanocomposite to sense Urine Ubiquitin Conjugating Enzyme E2 C (UBE2C), the nanocomposite's interactions with the enzyme was studied using a modeling model, and then the PAM\ZnO nanocomposite was prepared and studied with spectroscopic technique. Consequently, the Fourier Transform Infrared (FTIR) spectra for PAM\ZnO resulted in peaks in the 400 - 600 cm-1 range that vanished in acidic media. Density functional theory (DFT) calculations were performed at B3LYPL using the basis set 6-31G on PAM\ZnO nanocomposites with cysteine 114. The findings of the HOMO/LUMO bandgap energy, total dipole moment (TDM), and Molecular Electrostatic Potential (MESP) indicated that the effect of ZnO in the presence of PAM gives a nanocomposite with high electronic characteristics with a TDM ranging from 5.4464 to 12.3348 Debye, and bandgap (ΔE) 0.19965 to 0.28302 eV. A variation in the electrostatic characteristics of this composite followed the addition of Cystine 114. The distinctive properties of such nanocomposite PAM/ZnO enable usage in biosensor applications for bladder cancer. Finally, the FTIR spectrum showed that the estimated model fits as a proper biosensor. [ABSTRACT FROM AUTHOR]

Introduction: In Egypt, bladder cancer (BC) represents about 8.7% of cancers in both sexes. In Egyptian men, it accounts for over 30% of all cancers, which makes it the second most frequent cancer. The standard curative treatment for patients with muscle-invasive bladder cancer (MIBC) has been radical cystectomy (RC) with urinary diversion and pelvic lymphadenectomy. Concomitant chemoradiation therapy (CCRT) in MIBC appears to produce results that are comparable to those of RC. Material and methods: Between January 2018 and March 2021, 34 BCdiagnosed patients, who refused RC, were enrolled. They received transurethral resection of the bladder tumour (TURBT) followed by 3 cycles of neoadjuvant chemotherapy (NACT) with gemcitabine, cisplatin, and CCRT. Concomitant chemoradiation therapy with cisplatin, as a chemosensitizer, was administered to patients who experienced a complete response (CR) and a partial response (PR) ≥ 50%. Results: Following NACT, CCRT was given to 27 patients (79.45%) who had either a PR > 50% or CR. Seven patients (20.5%) showed PR below 50%, stable disease, or progressive disease; 4 of them underwent RC followed by postoperative radiation. The average follow-up period was 46 months (range: 6-52 months). Twenty-three patients (67.6%) were still alive at the last check-up. Disease-free survival and 3-year overall survival were 70.8% and 65.1%, respectively. Conclusions: Bladder preservation provides survival rates comparable to those of MIBC patients, but with a higher quality of life. The findings show good survival rates without metastasis; nevertheless, more multicentre trials with larger sample sizes and longer follow-up periods are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background Robotic-assisted radical cystectomy (RARC) is a well-known standard procedure for muscle-invasive bladder cancer. However, it remains controversial whether extracorporeal urinary diversion (ECUD) or intracorporeal urinary diversion (ICUD) is superior in this technique. We have developed a HYBRID method that combines ECUD and ICUD to retain the advantages of each. The purpose of this study was to compare perioperative outcomes between HYBRID and ECUD in RARC and to evaluate the usefulness of the HYBRID method. Methods We retrospectively analyzed the perioperative outcomes of 36 consecutive bladder cancer patients who underwent RARC with ileal conduit at our institution between March 2013 and December 2021. Propensity-score matching was used to align patient backgrounds between the HYBRID and ECUD groups. Results After matching, 12 cases were selected for each group. There was no significant difference in patient demographics between the groups except for the rate of neoadjuvant chemotherapy. Mean console time was significantly longer in the HYBRID group due to intracorporeal manipulation; however, a relatively favorable trend of mean blood loss was observed in this group. There was no significant difference between the groups in terms of positive surgical margin, mean number of lymph node removed, or positive lymph node. The incidences of complications associated and nonassociated with the urinary tract and grade =III complications at postoperative day (POD) 0-30 and 31-90 were similar between the groups. In the HYBRID group, no complications non-associated with the urinary tract or grade =III complications were observed at POD 31-90. Conclusion The HYBRID method takes advantage of the benefits of both ICUD and ECUD and is a highly applicable technique that can be used in a variety of patient backgrounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite advances in intravesical therapy and surgery, up to 30% of NMIBC suffer progression to MIBC. OBJECTIVES: To identify the valuable prognostic biomarkers, we analyzed the immunohistochemical expression of Sox2, YAP1, and IMP3 in 60 cases of NMIBC who underwent TURBT with adjuvant intravesical bacillus-Calmette-Guerin (BCG). METHODS: The immunohistochemical expression was done on a sixty patients who complained from primary papillary superficial transitional cell carcinoma (TCC) of the urinary bladder (Stage Ta-T1).Their predicting role for recurrence, progression, progression-free survival (PFS), and recurrence-free survival (RFS) was assessed. RESULTS: High Sox2 expression was observed in 55% of NMIBC cases, and it was significantly associated with the tumor size, grade, and stage (p <0.001 for each). High YAP1 was noted in 33.3% of the cases, and its expression was significantly associated with the tumor size, grade, and stage (p <0.001 for each). Strong IMP3 expression was detected in 45% of the cases, and it was associated with the tumor size, grade, and stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high Sox2, high YAP1, and Strong IMP3 expression exhibited a potent relation with tumor recurrence, progression, and shorter RFS & PFS. CONCLUSIONS: High Sox2, high YAP1, and strong IMP3 could be considered as adverse prognostic factors of tumor recurrence and progression in NMIBC, and these patients should be followed carefully. Therefore, we suggest that Sox2, YAP1 and IMP3 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients. [ABSTRACT FROM AUTHOR]

We evaluated long-term outcomes of small cell carcinoma of the bladder (SCCB), a rare, aggressive disease. Among 199 patients with SCCB treated from 1990 to 2015, those with nonmetastatic disease had excellent longterm survival following neoadjuvant chemotherapy with 5-year disease-free survival rate of 50%. Patients with metastases had poor survival, with median overall survival of 10.3 months. Pathologic downstaging following neoadjuvant chemotherapy was associated with superior survival and ERCC2 mutations conferred increased likelihood of pathologic response. Introduction: Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). Patients and Methods: Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. Results: One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (< pT2pN0) and pathologic complete response (pT0pN0) rates of 48% and 38%, respectively, with median follow-up of 7.2 years, and median DFS and OS of 5.6 and 14.5 years, respectively. NAC responders (< ypT2N0) had superior median DFS (14.5 vs. 0.6 years, hazard ratio [HR] 0.24, P < .001) and OS (14.5 vs. 2.5 years, HR 0.31, P = .002). DFS rates for responders and nonresponders were 76% and 27% at 5 years, and 71% and 23% at 10 years, respectively. Local and central nervous system recurrences were infrequent. Median progression-free survival (PFS) and OS for M1 disease were 6.9 and 10.3 months, respectively. Genomic profiling was performed on 47 NAC patients. Loss of ERCC2 function was significantly enriched among those with pathologic complete response to NAC (mutations present in 50% of pathologic complete responders vs. 15% nonresponders, P = .045). Conclusion: M0 SCCB is chemosensitive and patients have excellent long-term survival following response to NAC. Patients with M1 disease have poor survival despite systemic therapy. Loss-of-function mutations of ERCC2 were associated with pathologic complete response to NAC. [ABSTRACT FROM AUTHOR]

To obtain a better basis for patient counseling, we evaluated postoperative complications after radical cystecomy and creation of ileum conduit or neobladder in a contemporary series of bladder cancer patients. Our multi-institution approach (135 different hospitals in Germany) with prospective documentation at inpatient rehabilitation revealed a significantly higher complication rate than previously published. Risk factors for severe complications were creation of a neobladder and higher comorbidity. Purpose: To examine postoperative complications after radical cystectomy (RC) and creation of an ileum conduit (IC) or a neobladder (NB), and to identify preoperative risk factors in a contemporary series of bladder cancer patients. Patients and Methods: The study relied on prospectively collected data for 842 patients, who underwent inpatient rehabilitation (IR) after RC and urinary diversion (IC n = 447, NB n = 395) between April 2018 and December 2019. Postoperative complications until the end of IR were assessed according to the Clavien-Dindo classification. Uni- and multivariate analyses were performed to identify predictors for complications. Results: A total of 2689 complications occurred in 813 patients (96.6%). High-grade complications occurred more frequently before IR onset (25.5% vs. 5.7%; P < .001), whereas a higher percentage of low-grade complications occurred during IR (89.0% vs. 77.8%; P < .001). The most common complication categories were genitourinary (60.9%), infectious (54.0%) and gastrointestinal (49.2%). Rates of high-grade complications do not differ between IC and NB patients (26.8% vs. 31.6%, P = .126). Independent predictors for overall complications were NB (odds ratio [OR] 21.520; P < .001), age ≥70 years (OR 2.522; P = .027) and higher body mass index (OR 1.153, P = .008). Risk factors for high-grade complications were NB (OR 1.448; P = .039) and Charlson Comorbidity Index ≥2 (OR 1.999; P = .001). Hospital readmission rate was 9.4%. Conclusion: Our study revealed significantly higher overall and high-grade complication rates after RC with IC or NB creation than previously published. A high percentage of low-grade complications occur after hospital discharge. The hospital readmission rate was lower compared to historical data. [ABSTRACT FROM AUTHOR]

Objective: Radical cystectomy with extended pelvic lymph node (LN) dissection is a gold standard surgical treatment for muscle-invasive bladder cancer which is a common urological malignancy in elderly people. Despite common surgical technique is a transperitoneal approach, we aimed to analyze the benefit of extraperitoneal approach radical cystectomy in the gastrointestinal system. Materials and Methods: We retrospectively analyzed a total number of 110 (52 intraperitoneal and 58 extraperitoneal) radical cystectomy patients operated extraperitoneal or transperitoneal by 2 expert urologists between January 2016 to December 2019 in this study. All operated patients had indications for radical cystectomy and extended LN dissection and Wallace type ileal loop were performed adding to the operations. Patients have available data were included in this study and complications were assessed by Clavien- Dindo classification system. Results: The median age of a total number of 110 patients was 66 (minimum: 43 - maximum: 82) years. There were no differences between groups in terms of surgical region infection, urinary leakage, ileus treated surgically, and emergency admission after discharge of patients. Twenty-four (46.1%) patients in the transperitoneal group needed for erythrocyte transfusion whereas, 16 (27.5%) patients in the extraperitoneal approach group (p=0.04). Additionally, 13 (19.2%) patients in the transperitoneal group had ileus treated conservatively, whereas, 8 (13.7%) patients in the extraperitoneal approach group (p=0.02). Conclusion: Extraperitoneal approach and retroperitonealization of an ileal loop in radical cystectomy are safe and effective on oncological surgical principles. It may also provide better gastrointestinal motility after surgery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prognosis of patients with T1N0M0 urothelial carcinoma with squamous differentiation (UCSD) or glandular differentiation (UCGD) because it has not been determined whether these variant histologies behave more aggressively than pure urothelial carcinoma (PUC). Patients and Methods: Ninety-nine patients diagnosed with pT1N0M0 bladder cancer and treated conservatively with transurethral resection of bladder tumor at Kanazawa University Hospital between 2007 and 2019 were included in this study. The overall survival, cancer-specific survival (CSS), and recurrence-free survival of the variant histology and PUC groups were evaluated and compared. Results: The variant histology group had significantly lower overall survival (p=0.006) and CSS (p=0.0095) than the PUC group did. Variant histology was found to be an independent prognostic factor in univariate and multivariate analyses for overall survival and CSS. On the other hand, no significant difference in progression-free survival was observed between the two groups (p=0.439). However, the variant histology group had significantly lower overall survival (p=0.004) and CSS (p=0.004) after progression. Conclusion: The prognosis for patients with pT1 bladder cancer with UCSD or UCGD treated conservatively with transurethral resection of bladder tumor was poor. Considering the worse prognosis of these patients after stage progression, early radical cystectomy could be recommended. [ABSTRACT FROM AUTHOR]

This retrospective analysis investigated the predictive and prognostic value of serum gammaglutamyltransferase (GGT) in 324 patients undergoing RC for invasive bladder cancer (BC). Elevated preoperative serum GGT levels was associated with increased risk of locally advanced BC and mortality after RC. The data suggest that GGT levels may be a useful for improved prognostication in invasive BC. Introduction: The aim of the study was to elucidate the predictive and prognostic value of serum gammaglutamyltransferase (GGT) in patients with invasive bladder cancer (BC). Patients and Methods: Preoperative serum GGT concentrations were assessed in 324 patients treated with RC for cM0 BC between 2002 and 2013. Laboratory values were obtained 1 to 3 days prior to RC. Uni- and multivariable analyses were carried out to evaluate clinicopathologic risk factors for survival. The median follow-up was 36 months (IQR: 10-55). Results: Elevated preoperative GGT levels were diagnosed in 77 patients (23.8%). Elevated GGT was significantly associated with higher ECOG PS and tumor stage (both P = .001), lymph-node tumor involvement (P < .001), positive surgical margins (P = .018), lymphovascular invasion (P = .024), muscle-invasive disease at primary diagnosis (P = .033), increased tumor size (P = .035), hydronephrosis at RC (P = .049) and increased preoperative CRP, GPT and GOT levels (both P < .001). Patients with elevated GGT had decreased 3-year overall (49.2% vs. 69.6%; P = .005) and cancer-specific survival (71.1% vs. 80.9%; P = .042) compared with patients with normal levels. On multivariable analysis, advanced tumor stage (P = .032), lymph node positive disease (P = .030), positive soft tissue surgical margins (P = .014), hydronephrosis at RC (both P = .010), higher ECOG performance status and elevated GGT (P = .043) levels were independent predictors of all-cause mortality. Conclusion: Elevated preoperative serum GGT levels are associated with increased risk of locally advanced BC and mortality after RC. These data suggest that GGT levels may be useful for improved prognostication in invasive BC. [ABSTRACT FROM AUTHOR]