Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

Clinical characteristics and factors associated with survival rate of patients with non-muscle invasive bladder cancer attending at a Tertiary Hospital in Somalia.

BACKGROUND: A few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC. METHOD: This six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients. RESULTS: The mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310-2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607-5.614),p < 0.001], tumour location [1.135(0.806-1.172),p < 0.001], number [0.510(0.410-0.920),p = 0.03], tumour size [1.523(0.936-1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972-4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172-2.154),p < 0.001], and follow-up compliance [3.376(2.633-5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28). CONCLUSION: Our study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country.

Association between CYP1A2 gene variants -163 C/A (rs762551) and -3860 G/A (rs2069514) and bladder cancer susceptibility.

BACKGROUND: Bladder cancer (BLCA) poses a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options. AIMS AND OBJECTIVES: This study aims to investigate the association between two specific polymorphisms, CYP1A2-163 C/A and CYP1A2-3860G/A, within the Cytochrome P450 1A2 (CYP1A2) gene and susceptibility to BLCA. METHODS: The study employed a case-control design, genotyping 340 individuals using Polymerase Chain Reaction-High-Resolution Melting Curve (PCR-HRM). Various genetic models were applied to evaluate allele and genotype frequencies. Genetic linkage analysis was facilitated using R packages. RESULTS: The study reveals a significant association with the - 163 C/A allele, particularly in the additive model. Odds ratio (OR) analysis links CYP1A2-163 C/A (rs762551) and CYP1A2-3860G/A(rs2069514) polymorphisms to BLCA susceptibility. The rs762551 C/A genotype is prevalent in 55% of BLCA cases and exhibits an OR of 2.21. The A/A genotype has an OR of 1.54. Regarding CYP1A2-3860G/A, the G/A genotype has an OR of 1.54, and the A/A genotype has an OR of 2.08. Haplotype analysis shows a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. This study underscores associations between CYP1A2 gene variants, particularly rs762551 (CYP1A2-163 C/A), and an increased susceptibility to BLCA. Haplotype analysis of 340 individuals reveals a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. CONCLUSION: In conclusion, the - 163 C/A allele, C/A genotype of rs762551, and G/A genotype of rs2069514 emerge as potential genetic markers associated with elevated BLCA risk.

Influence of lamina propria invasion extension on T1 high-grade non-muscle-invasive bladder cancer in patients undergoing BCG or radical cystectomy.

OBJECTIVE: To evaluate the prognostic value of T1 substaging in patients treated with bacillus Calmette-Guérin (BCG) or immediate radical cystectomy (iRC). MATERIALS AND METHODS: We performed an institutional review board-approved retrospective study analysing non-muscle-invasive bladder cancer (NMIBC) patients with pT1 disease treated with either BCG or iRC between 2000 and 2020. Lamina propria (LP) invasion characteristics were extracted from the pathology report. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS) and metastasis-free survival (MFS). Multivariable Cox models were used to determine the association between progression-free survival (PFS) and characteristics in the BCG cohort. A logistic regression model explored the relationship between T1 substaging and upstaging to >pT2 at iRC. RESULTS: A total of 411 T1 high-grade patients were identified. LP invasion characteristics were as follows: not specified: 115 (28%); focal/superficial (F/S): 147 (35.8%); and extensive/multifocal (E/M): 149 (36.2%). Overall, 303 patients (73.7%) received BCG, and 108 patients (26.3%) underwent iRC. The median (interquartile range) follow-up was 53 (32-96) months. Patients with E/M LP invasion were significantly more likely to undergo iRC (34% vs. 19%; P = 0.003). Patients with E/M LP invasion showed poorer MFS and CSS compared to those with F/S LP invasion when treated with BCG but not when treated with iRC. Among BCG-treated patients, progression occurred in 41 patients and E/M LP invasion was independently associated with progression after BCG (hazard ratio 5.3, 95% confidence interval [CI] 2.2-13.1; P < 0.001). T1 substaging was not associated with upstaging at RC (odds ratio 3.15, 95% CI 0.82-12.12; P = 0.095). CONCLUSIONS: Extensive/multifocal LP invasion was associated with poor PFS, MFS and CSS in patients treated with BCG. T1 substaging provides valuable prognostic information and should be reported in pathology reports.

Prognostic role of the neutrophil/lymphocyte ratio in high-risk BCG-naïve non-muscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel.

OBJECTIVES: To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic. RESULTS: The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 109/L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value. CONCLUSION: Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding.

Long-term outcomes and cost savings of office fulguration of papillary Ta low-grade bladder cancer.

OBJECTIVES: To assess whether office-based fulguration (OF) under local anaesthesia for small, recurrent, pathological Ta low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is an effective alternative to transurethral resection of bladder tumour (TURBT), avoiding the costs and risks of procedure, and anesthesia. PATIENTS AND METHODS: Of 521 patients with primary TaLG NMIBC, this retrospective study included 270 patients who underwent OF during follow-up for recurrent, small, papillary LG-appearing tumours at a university centre (University Health Network, University of Toronto, Canada). We assessed the cumulative incidence of cancer-specific mortality (CSM) and disease progression (to MIBC or metastases), as well as possible direct cost savings. RESULTS: In the 270 patients with recurrent TaLG NMIBC treated with OF, the mean (sd) age was 64.9 (13.3) years, 70.8% were men, and 60.3% had single tumours. The mean (sd, range) number of OF procedures per patient was 3.1 (3.2, 1-22). The median (interquartile range) follow-up was 10.1 (5.8-16.2) years. Patients also underwent a mean (sd) of 3.6 (3.0) TURBTs during follow-up in case of numerous or bulkier recurrence. In all, 44.4% of patients never received intravesical therapy. The 10-year incidence of CSM and progression were 0% and 3.1% (95% confidence interval 0.8-5.4%), respectively. Direct cost savings in Ontario were estimated at $6994.14 (Canadian dollars) per patient over the study follow-up. CONCLUSIONS: This study supports that properly selected patients with recurrent, apparent TaLG NMIBC can be safely managed with OF under local anaesthesia with occasional TURBT for larger or numerous recurrent tumours, without compromising long-term oncological outcomes. This approach could generate substantial cost-saving to healthcare systems, is patient-friendly, and could be adopted more widely.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

Multiparametric Magnetic Resonance Imaging in the follow-up of non-muscle-invasive bladder tumors after intravesical instillations: a promising tool.

PURPOSE: The standard follow-up for non-muscle-invasive bladder cancer is based on cystoscopy. Unfortunately, post-instillation inflammatory changes can make the interpretation of this exam difficult, with lower specificity. This study aimed to evaluate the interest of bladder MRI in the follow-up of patients following intravesical instillation. METHODS: Data from patients who underwent cystoscopy and bladder MRI in a post-intravesical instillation setting between February 2020 and March 2023 were retrospectively collected. Primary endpoint was to evaluate and compare the diagnostic performance of cystoscopy and bladder MRI in the overall cohort (n = 67) using the pathologic results of TURB as a reference. The secondary endpoint was to analyze the diagnostic accuracy of cystoscopy and bladder MRI according to the appearance of the lesion on cystoscopy [flat (n = 40) or papillary (n = 27)]. RESULTS: The diagnostic performance of bladder MRI was better than that of cystoscopy, with a specificity of 47% (vs. 6%, p < 0.001), a negative predictive value of 88% (vs. 40%, p = 0.03), and a positive predictive value of 66% (vs. 51%, p < 0.001), whereas the sensitivity did not significantly differ between the two exams. In patients with doubtful cystoscopy and negative MRI findings, inflammatory changes were found on TURB in most cases (17/19). The superiority in MRI bladder performance prevailed for "flat lesions", while no significant difference was found for "papillary lesions". CONCLUSIONS: In cases of doubtful cystoscopy after intravesical instillations, MRI appears to be relevant with good performance in differentiating post-therapeutic inflammatory changes from recurrent tumor lesions and could potentially allow avoiding unnecessary TURB.

Preoperative blood-based nutritional biomarkers as significant prognostic factors after intravesical BCG therapy in patients with non-muscle-invasive bladder cancer.

The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33-0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32-0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41-0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33-0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27-0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35-0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy.

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer.

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. Most people have surgery to remove the cancer cells while leaving the rest of the bladder intact. This is called transurethral resection of a bladder tumor (TURBT). For people with high-risk NMIBC, a medicine called Bacillus Calmette-Guérin (BCG) is placed directly inside the bladder after TURBT. A 'high risk' classification means that the cancer is more likely to spread or come back after treatment. Some people's cancer does not respond to BCG or returns after BCG treatment. Researchers are currently looking at whether BCG combined with other immunotherapies may prevent cancer growth more than BCG on its own. Immunotherapy helps the immune system recognize and kill cancer cells. Sasanlimab is an immunotherapy medicine that is not yet approved to treat people with NMIBC. It is given as an injection under the skin. In this CREST study, researchers are looking at how safe and effective sasanlimab plus BCG is for people with high-risk NMIBC. Around 1000 people are taking part in CREST. They must have had TURBT 12 weeks or less before joining the study. Researchers want to know how long people live without certain events occurring, such as bladder cancer cells returning. A plain language summary of this article can be found as Supplementary Material. Clinical Trial Registration: NCT04165317; 2019-003375-19 (EudraCT) (ClinicalTrials.gov).

N-803 Plus BCG Treatment for BCG-Naïve or -Unresponsive Non-Muscle Invasive Bladder Cancer: A Plain Language Review.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC).One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCGunresponsive). WHAT HAPPENED IN THE STUDIES?: In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 µg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 µg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 µg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row. WHAT WERE THE KEY TAKEAWAYS?: N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease.Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).

Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

Nomogram for customized recurrence prediction in primary non-muscle-invasive bladder cancer based on routine blood and urine parameters.

PURPOSE: A prevalent condition with a high probability of recurrence, non-muscle invasive bladder cancer (NMIBC) necessitates lifetime surveillance. In patients with pathologically confirmed NMIBC, our goal was to create a unique nomogram to predict recurrence after transurethral resection of bladder tumor (TURBT). METHODS: Our institution's 91 NMIBC patients with complete follow-up data between January 2017 and February 2021 were included in the retrospective analysis. The nomogram predicting the 0.5, 1, 2 and 3-year likelihood of recurrence was created using multivariate Cox proportional hazard models to find the significant determinants of recurrence. Using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA), we internally validated the nomogram. RESULTS: The significant factors related to NMIBC recurrence were age, blood platelet count, especially for the urine leukocyte count and mucus filament. The constructed nomogram performed well in the customized prediction of NMIBC recurrence at 6th, 12th, 24th and 36th month, of which the C-index was 0.724. The calibration curve and the ROC curve both validated the prediction accuracy. On DCA, the nomogram presented good net benefit gains across a wide range of threshold probabilities. Furthermore, the Nomogram-related risk score was used to divide the patient population into two groups with significant recurrence disparities. CONCLUSION: For the prediction of NMIBC recurrence, our unique nomogram demonstrated a respectable degree of discriminative capacity, sufficient calibration, and considerable net benefit gain. There will be a need for additional internal and external validation.

Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

The Efficacy and Safety of Hyperthermia Intravesical Chemotherapy in the Treatment of Non-Muscle-Invasive Bladder Cancer: A Meta-Analysis.

INTRODUCTION: The current treatment of non-muscle-invasive bladder cancer is suboptimal. However, in recent years, hyperthermia intravesical chemotherapy (HIVEC) has emerged as a more effective alternative to conventional bladder perfusion. This novel treatment approach appears to have a similar therapeutic effect as Bacillus Calmette-Guérin (BCG) perfusion. This study aims to evaluate the safety and effectiveness of HIVEC compared to conventional bladder perfusion chemotherapy for non-muscle-invasive bladder cancer. Additionally, it aims to evaluate the safety and effectiveness of HIVEC in comparison to BCG perfusion therapy for non-muscle-invasive bladder cancer. METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases to gather relevant studies on HIVEC for non-muscle-invasive bladder cancer. The analysis of the collected data was carried out using RevMan 5.3 software. RESULTS: A total of 8 randomized controlled trials were included in this meta-analysis, involving 1,203 patients. Among them, 629 cases received HIVEC, 419 cases received conventional bladder perfusion chemotherapy with mitomycin C, and 155 cases received BCG. The combined analysis revealed that the recurrence rate of bladder hyperthermic perfusion was significantly lower than that of conventional perfusion chemotherapy (RR = 0.65, 95% CI: 0.52, 0.82, p = 0.0003). However, there was no significant difference in recurrence rate between HIVEC and BCG perfusion (RR = 0.78, 95% CI: 0.56, 1.09, p = 0.14). Furthermore, no significant difference was found in the progression rate between the HIVEC group and either the conventional bladder chemotherapy group (RR = 1.08, 95% CI: 0.52, 2.26, p = 0.83) and the BCG perfusion group (RR = 0.48, 95% CI: 0.19, 1.25, p = 0.13). However, compared with the conventional bladder perfusion chemotherapy group, there was no significant statistical difference in adverse events between the bladder hyperthermia chemotherapy group and the conventional bladder perfusion chemotherapy group (RR 1.08, 95% CI: 0.80, 1.45, p = 0.63). No significant difference in the incidence of adverse events was observed between HIVEC and BCG perfusion (RR 1.03, 95% CI: 0.83, 1.29, p = 0.79). CONCLUSION: The existing results indicate that HIVEC, when compared to conventional bladder perfusion chemotherapy, can lower the recurrence rate of non-muscle-invasive bladder cancer. However, it does not significantly affect the progression rate. There was no statistically significant difference observed in the incidence of adverse events between the use of HIVEC and conventional chemotherapy. Additionally, there was no significant difference in the recurrence rate, progression rate, and incidence of adverse events when compared to BCG.

Application of PLK1 and HOXA13 Gene Expression Levels in Urine in the Diagnosis of Non-muscle Invasive Bladder Cancer.

Bladder cancer is the most common urinary tract neoplasm, affecting many people annually. Current diagnostic and surveillance methods for bladder cancer are frequently invasive and lack sensitivity and specificity. This study aimed to develop an accurate and non-invasive urine-based gene expression assay, including fibroblast growth factor receptor 3 (FGFR3), homeobox A13 (HOXA13), and polo-like kinase 1 (PLK1), to diagnose non-muscle-invasive bladder cancer (NMIBC) at stages Ta and T1. The samples were acquired from 62 patients with NMIBC, 31 control individuals, and 31 patients with non-cancerous genitourinary tract diseases. The expression levels of three relevant genes were determined using quantitative RT-PCR. In addition, the sensitivity and specificity of the data for these genes were computed. Our results showed that PLK1, HOXA13, and FGFR3 expressions of genes were significantly elevated in patients compared to the control groups (p = 0.0001; p = 0.039). The sensitivity and specificity for the FGFR3 gene were 55% and 76%, respectively (p = 0.39). These parameters for HOXA13 were 100% and 93% (p = 0.0001) and for PLK1 were 100% and 86% (p = 0.0001) for diagnosing and monitoring NMIBC. HOXA13 and PLK 1 exhibited adequate specificity and sensitivity for diagnosis. The results of this research showed that despite the higher expression of these genes in urine, only HOXA13 and PLK1 had sufficient and proper specificity and sensitivity, so the urinary expression of these two genes can be used in future studies for diagnosis and monitoring in cancer bladder.

A novel laser resection approach: efficacy of rotatable bi-channel en bloc resection of bladder tumor in a pilot in-vivo study.

En bloc resection of bladder tumor (ERBT) involves removing bladder tumors and their base. Laser resection has been used to reduce complications including bleeding and obturator nerve reflex (ONR). We developed a novel approach (rotatable bi-channel en bloc resection of bladder tumor (RBC-ERBT)) and assessed its efficacy in a pilot in-vivo study to enhance laser ERBT's applicability in challenging bladder regions. In the laser RBC-ERBT procedure, lesions were excised by inserting a holmium laser through the rotating external working channel, while forceps were inserted through the internal working channel provided traction on the tissue. Fifteen laser RBC-ERBT procedures were performed in five different bladder areas of three live pigs. The technical success rate (TSR), procedure time, lesion size, occurrence of complications (bleeding, perforation, ONR), and detrusor muscle (DM) presence rate and DM thickness were evaluated. All 15 procedures were performed with a 100% TSR. The resections were successful in all bladder regions (posterior, left, right and anterior walls and dome). Median procedure time was 20 min. The resected specimen size was 10 mm × 7 mm to 17 mm × 13 mm. Mild bleeding occurred in two procedures (13.3%) but was effectively managed. No incidents of ONR or perforation were observed. Histological examination confirmed presence of DM in all specimens with a median DM thickness of 1.26 mm. Our pilot in-vivo study suggested the feasibility and effectiveness of laser RBC-ERBT for bladder tumors in various locations. This technique offers effective traction, improved visualization, and enhanced laser accessibility. Further studies are required to validate its effectiveness in humans.

Location-specific diagnostic efficiency of photodynamic diagnosis-guided biopsy in bladder mapping biopsies.

BACKGROUND: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumors (TURBT) has emerged as a promising complementary tool to white light (WL) cystoscopy, potentially improving cancer detection and replacing conventional mapping biopsies. This study aimed to investigate the diagnostic accuracy of PDD by anatomical locations in mapping biopsies through lesion-based analysis. METHODS: PDD and WL findings were prospectively recorded in 102 patients undergoing mapping biopsies and PDD-assisted TURBT using oral 5-aminolevulinic acid. We evaluated 673 specimens collected from flat tumor or normal-looking lesions on WL cystoscopy, after excluding 98 specimens collected from papillary or nodular tumors. RESULTS: Among the 673 lesions, cancer was detected in 110 (16%) by lesion-based analysis. PDD demonstrated significantly higher sensitivity (65.5% vs. 46.4%, p < 0.001) and negative predictive value (92.5% vs. 89.5%, p < 0.001) compared to WL. The sensitivity of PDD findings varied by location: posterior (100%), right (78.6%), dome (73.3%), left (70.6%), trigone (58.8%), bladder neck (41.7%), anterior (40.0%), and prostatic urethra (25.0%). Incorporating targeted biopsies of specific locations (bladder neck, anterior, and prostatic urethra) into the PDD-guided biopsies, regardless of PDD findings, significantly increased the overall sensitivity from 65.5% to 82.7% (p = 0.001). CONCLUSIONS: This study first demonstrated the detection rate of location-specific mapping biopsies using PDD, revealing difficulties in accuracy assessment in areas susceptible to tangential fluorescence. While PDD-guided biopsy improves cancer detection compared to WL cystoscopy even for flat tumors or normal-looking lesions, more careful decisions, including mapping biopsies, may be beneficial for an assessment in these tangential areas.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

A surgical checklist for optimizing the quality and outcomes of transurethral resection of bladder tumors: A literature review.

To preserve the bladder without compromising survival, further treatments need to be optimized to prevent the recurrence and progression of non-muscle invasive bladder cancer. In clinical practice, transurethral resection of bladder tumors is essential for bladder cancer management. The primary goal of surgery is to achieve accurate pathological evaluation and complete resection of bladder cancer; high resection quality is required for the procedure. A representative surrogate indicator of the resection quality is the presence of the detrusor muscle in the resection specimen. Therefore, complete visual resection of bladder cancer with a muscle layer is crucial for decreasing the recurrence and progression rates of non-muscle-invasive bladder cancer. However, this procedure is complex and requires sufficient experience and knowledge to be performed thoroughly, safely, and efficiently. Surgical checklists represent an approach to filling the knowledge and experience gaps and improving the quality and safety of surgery. By checking items during transurethral resection, it is expected that the recording of risk factors related to recurrence and progression will improve, the rate of visually complete resection with muscles will increase, and the rate of intravesical recurrence will decrease. The simplicity of checklists is an additional benefit. In recent years, surgical checklists have received increasing attention in order to achieve high-quality resections and reduce disparities between surgeons and institutions. This literature review outlines the evolving treatment strategies for patients with non-muscle-invasive bladder cancer, focusing on surgical checklists for the transurethral resection of bladder tumors.