Search

Purpose: Many patients receiving intravesical BCG treatment for non-muscle-invasive bladder cancer experience high recurrence rates despite initial adequate response. In this study, the effectiveness of intravesical chemohyperthermia (CHT) with mitomycin C (MMC) was evaluated in patients who developed relapse after intravesical BCG treatment or could not tolerate the treatment and could not undergo radical cystectomy for any reason. Materials and methods: 59 patients who underwent complete bladder tumour resection, who had a T1 high-grade tumour and no variant histology was observed in the pathology, and who had previously received intravesical BCG treatment were included in the study. Adjuvant treatment with intravesical CHT-MMC was applied. As a treatment protocol, induction was applied once a week for 6 weeks, followed by maintenance treatment 6 times at 4-week intervals. Each treatment session, it involved bladder wall hyperthermia with a temperature of up to 42 ℃ ± 2 and intravesical administration of 20 mg/50 ml MMC solution twice at 30-min intervals. Results: Recurrence-free survival after warm mitomycin was 58.7 and 48%, respectively, at 24 months and 44 months, and progression-free survival was 72.6 and 66.2%, respectively. In the subgroup analysis performed according to the number of tumours at diagnosis (single, 2–5, more than 5), recurrence-free survival rates were 81.8%, 48.2% and 11%, respectively, during the median follow-up period of 44 months. Conclusions: Intravesical CHT-MMC can be considered as an alternative treatment in selected well-informed patients with non-muscle-invasive papillary urothelial carcinoma who are unresponsive to BCG or intolerant to BCG. Prospectively designed studies with larger number of patients are needed. [ABSTRACT FROM AUTHOR]

The International Bladder Cancer Group recommends various bladder-sparing therapy (BST) options for patients with bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer who refuse or are ineligible for radical cystectomy. BST selection should be personalized to each patient, and clinical trial participation is encouraged given the modest efficacy of the BST options available. There has been a recent surge in the development of agents for bacillus Calmette-Guérin–unresponsive (BCG-U) non–muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC. [ABSTRACT FROM AUTHOR]

This overview of the 2024 European Association of Urology guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of non–muscle-invasive bladder cancer patients. These guidelines are designed for effective integration into clinical practice. This publication represents a summary of the updated 2024 European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ. The information presented herein is limited to urothelial carcinoma, unless specified otherwise. The aim is to provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation. For the 2024 guidelines on NMIBC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with NMIBC. The guidelines stress the importance of defining patients' risk stratification and treating them appropriately. This overview of the 2024 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of NMIBC. These guidelines are designed for effective integration into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract 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

Non-muscle-invasive bladder cancer (NMIBC) encompasses approximately three-quarters of all bladder cancer (BC) diagnoses. Intravesical Bacillus Calmette-Guerin (BCG) has been the long-standing gold standard treatment for patients following endoscopic resection. However, despite reasonable efficacy, recurrence rates are still suboptimal, and this, combined with treatment tolerability and BCG shortages, has prompted an investigation into alternative treatment modalities. Advances in this landscape have been predominantly for patients with BCG-unresponsive disease, and there are currently four FDA-approved treatments for these patients. More recently, trials have emerged looking for alternatives to BCG for patients who are treatment-naïve. We performed a literature search via PubMed to find recent publications on alternatives to BCG, as well as a search on clinicaltrials.gov and recent conference presentations for ongoing clinical trials. Studies have shown that combination intravesical chemotherapy, combination intravesical therapy with BCG, and combination intravenous therapy with BCG preliminarily have good efficacy and safety profiles in this disease space. Ongoing trials are underway, and we anticipate as these studies mature, there will be a shift in NMIBC treatment regimens. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Frequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.

OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is a relatively rare but aggressive type of urologic cancer that includes renal pelvic tumors and ureteral tumors with a poor prognosis. Full-length nephroureterectomy plus sleeve bladder resection is the standard treatment for the disease, but patients are prone to recurrence of bladder tumors after surgery. Intravesical infusion therapy is the main means to prevent the recurrence and progression of bladder cancer. Epirubicin and gemcitabine are widely used in clinical practice as first-line or salvage therapy for intravesical chemotherapy; however, the effi- cacy of these agents is rarely discussed. The purpose of this study was to investigate the effects of epirubicin and gemcitabine on the occurrence of bladder cancer after radical nephroureterectomy for UTUC and to analyze the risk factors affecting the recurrence of postoperative bladder cancer. PATIENTS AND METHODS: A total of 215 patients with diagnosed UTUC and treated in our hospital from June 2019 to August 2021 were retrospectively selected as the research subjects, and they were divided into an observation group (120 cases) and a control group (95 cases) according to different treatment methods. The patients in the control group were treated with epirubicin, while those in the observation group received gemcitabine. All patients were followed up by telephone or outpatient examination for 12 months to record the occurrence of adverse reactions. The occurrence of bladder cancer was recorded at 3 months, 6 months, and 12 months after the surgery. According to the occurrence of bladder cancer after surgery, the patients were divided into a bladder cancer group (63 cases) and a non-bladder cancer group (152 cases). Multivariate Logistic regression analysis was used to analyze the risk factors of bladder cancer after surgery. RESULTS: The total incidence of adverse reactions in the control group was 49.47%, which was higher than that in the observation group with 15.00% (p<0.01). The incidence of bladder tumors in the observation group and the control group was 0.00% and 2.11% at 3 months, 5.00% and 8.42% at 6 months, 13.33% and 15.79% at 12 months, without significant difference (p>0.05). After 12 months of perfusion, the levels of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in the two groups were significantly lower than those before perfusion (p<0.05). In the observation group, the levels of these three factors were slightly decreased compared with those in the control group, without a significant difference (p>0.05). Between the bladder cancer and non-bladder cancer groups, there were significant differences in tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer (p<0.05). The above indexes were all risk factors for postoperative bladder cancer (p<0.05). CONCLUSIONS: Epirubicin and gemcitabine reduced the occurrence of bladder cancer and effectively inhibited tumor angiogenesis after radical nephroureterectomy for UTUC. The tumor location, number of lesions, tumor stage, preoperative ureteral examination, and preoperative history of bladder cancer were risk factors for postoperative bladder cancer. [ABSTRACT FROM AUTHOR]

Bacillus Calmette-Guérin (BCG) is the standard treatment for patients with non-muscle invasive bladder cancer (NMIBC). Although this therapy has been effective, BCG resistance poses a significant challenge, highlighting the need for alternative treatment options. Possible alternative treatments include intravesical chemotherapy, immunotherapy, antibody-drug conjugates, device-assisted therapies, gene therapy, and radiotherapy. Although radical cystectomy is recommended after BCG failure, its high morbidity and considerable impact on patients' lives underscore the necessity of developing new treatment strategies. This review provides an outline of the current knowledge and ongoing research on alternative treatments for BCG-unresponsive high-risk NMIBC, aiming to improve patient outcomes. Considering the current global shortage of BCG, it is essential to prioritize alternative therapies as treatment options for patients with BCG-unresponsive NMIBC.

Surgical resection remains the prefer option for bladder cancer treatment. However, the effectiveness of surgery is usually limited for the high recurrence rate and poor prognosis. Consequently, intravesical chemotherapy synergize with immunotherapy in situ is an attractive way to improve therapeutic effect. Herein, a combined strategy based on thermo-sensitive PLEL hydrogel drug delivery system was developed. GEM loaded PLEL hydrogel was intravesical instilled to kill tumor cells directly, then PLEL hydrogel incorporated with CpG was injected into both groins subcutaneously to promote immune responses synergize with GEM. The results demonstrated that drug loaded PLEL hydrogel had a sol-gel phase transition behavior in response to physiological temperature and presented sustained drug release, and the PLEL-assisted combination therapy could have better tumor suppression effect and stronger immunostimulating effect in vivo. Hence, this combined treatment with PLEL hydrogel system has great potential and suggests a clinically-relevant and valuable option for bladder cancer.

Le traitement de référence chez les patients présentant une tumeur de vessie non répondeur à l'immunothérapie par BCG repose sur la cystoprostatectomie ou la pelvectomie antérieure. Cependant de nombreux patients ne sont pas éligibles à ce traitement chirurgical ou souhaitent une préservation vésicale. Les instillations intravésicales de Gemcitabine et Docétaxel sont une alternative (hors AMM). La procédure d'instillation comprend 1 cure d'induction par semaine pendant 6 semaines avec alcalinisation des urines avant chaque cure. Une cure d'entretien mensuelle pendant 1 an peut être réalisée en l'absence de récidive sur la cystoscopie de contrôle à 3 mois de la première dose d'induction. Le profil de tolérance de ce traitement est acceptable. Radical cystectomy is the standard treatment in patients with BCG unresponsive non-muscle invasive bladder cancer. However, many patients are not eligible for this surgical approach or seek bladder preservation. Intravesical instillations of Gemcitabine and Docetaxel are an alternative (off-label). The instillation procedure includes 1 induction course per week for 6 weeks with alkalinization of urine before each course. A monthly maintenance course for 1 year can be carried out in the absence of recurrence on control cystoscopy 3 months after the first induction dose. The safety profile of this treatment is acceptable. [ABSTRACT FROM AUTHOR]

Abstract Objective Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. Subjects and Methods This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). Results The median follow-up was 5.2 years. Compared with instillation for 1–2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3–6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27–12.41;0.26–9.28;0.07–0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. Conclusions In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.

Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy. • Erdafitinib prolonged RFS versus intravesical chemotherapy in papillary-only FGFR -altered BCG-treated high-risk NMIBC. • At median follow-up of 13.4 months, median RFS was not reached for erdafitinib and was 11.6 months for chemotherapy. • The observed RFS benefit for erdafitinib was further reflected by the 6- and 12-month RFS rates and subgroups tested. • In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. • These trial results validate FGFR inhibition as a promising treatment approach for NMIBC. [ABSTRACT FROM AUTHOR]

Abstract Purpose To clarify the necessity and effect of a single intraoperative instillation of chemotherapy during radical cystectomy. Methods Patients who underwent radical cystectomy for bladder cancer between January 2013 and April 2019 were retrospectively evaluated and divided into a non‐instillation group and an instillation group according to the intraoperative instillation of chemotherapy. Univariate and multivariate Cox regression was used to determine the clinical predictors of overall survival and disease‐free survival. Kaplan–Meier analysis and log‐rank tests were performed to analyze overall survival and disease‐free survival. Results Of the 320 patients who were enrolled in the study, 113 underwent radical cystectomy with intraoperative instillation of chemotherapy. Univariate Cox analysis showed that intraoperative instillation was not a risk factor for overall survival or disease‐free survival (HR: 1.04, 95% CI: 0.66–1.63, p = 0.864; HR: 1.11, 95% CI: 0.76–1.62, p = 0.602, respectively). As shown in the Kaplan–Meier analysis, no significant differences were noted in overall survival (p = 0.857) and disease‐free survival (p = 0.600) between the two groups. A subgroup analysis demonstrated that intraoperative instillation was not associated with a statistically better overall survival and disease‐free survival in the nonmuscle invasive (p = 0.852 and 0.836) and muscle‐invasive (p = 0.929 and 0.805) patients. Conclusion A single intraoperative instillation of chemotherapy during radical cystectomy was not related to better disease‐free survival or overall survival. It is unnecessary to consider single instillation of chemotherapy as a regular procedure during radical cystectomy.

AbstractPurpose To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine.Materials and methods A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed.Results A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h.Conclusion GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC.

Objective: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. Subjects and Methods: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). Results: The median follow-up was 5.2 years. Compared with instillation for 1–2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3–6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27–12.41;0.26–9.28;0.07–0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. Conclusions: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC. [ABSTRACT FROM AUTHOR]

Po-Ting Lin1 &ast;, Ming-Li Hsieh1,2 &ast;, Shih-Huan Su,1 Ying-Hsu Chang,2,3 Liang-Kang Huang,1,2 Yuan-Cheng Chu,1,2 Hung-Cheng Kan,1,2 Po-Hung Lin,1,2 Kai-Jie Yu,1,2 Cheng-Keng Chuang,1,2 Chun-Te Wu,1,2,4 See-Tong Pang,1,2 I-Hung Shao1,2,5 1Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 2Department of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Urology, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital and Chang Gung University, New Taipei, Taiwan; 4Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan; 5Cancer Genome Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan&ast;These authors contributed equally to this workCorrespondence: I-Hung Shao, Department of Medicine, Chang Gung University, No. 5, Fusing St., Gueishan Dist, Taoyuan City, Taiwan, Email ehomeshao68@gmail.comObjective: Among intravesical instillation protocol in patients with non-muscle-invasive bladder cancer (NMIBC), chemotherapy agents have been widely used during the bacillus Calmette-Guérin (BCG) shortage era since the patient might under the risk of BCG discontinuation. This study evaluates the efficacy of incomplete BCG instillation compared with pure chemotherapy instillation protocol.Materials and Methods: Patients newly diagnosed with intermediate- and high-risk NMIBC who received incomplete BCG intravesical instillation or chemotherapy instillation were retrospectively included. Patients were divided into three groups according to different intravesical instillation schedules: [BCG only], [BCG + Chemo], and [Chemo only]. Comparisons between these three groups were performed. Bladder recurrence-free survival (RFS) was analyzed as the primary endpoint.Results: A total of 475 patients who received intravesical instillations were enrolled. Compared to the [Chemo only] group, the [BCG + Chemo] group had significantly better bladder RFS (p = 0.027). Multivariate analysis of recurrence revealed the [BCG + Chemo] regimen has a hazard ratio 0.381 (95% CI 0.154– 0.941, p = 0.037). The total instillation number > 12 was associated with better RFS (p = 0.001) compared with other instillation numbers.Conclusion: For NMIBC patients facing the risk of unexpected BCG instillation interruption, instead of starting instillation with chemotherapy agents, receiving BCG first till stoppage then shifting to chemotherapy agents is recommended.Keywords: bladder cancer, NMIBC, intravesical instillation, intravesical chemotherapy, BCG, bladder recurrence

Results from HIVEC-II show no oncological benefit from chemohyperthermia over the control treatment. Adverse events following chemohyperthermia were low of grade and short-lived, although these patients were less likely to complete their treatment. Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non–muscle-invasive bladder cancer (NMIBC). To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC. HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital. Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min. The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat. A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51–69%) in the CHT arm and 60% (95% CI 50–68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62–1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09–10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83–9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77–8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control). CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment. The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non–muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the necessity and effect of a single intraoperative instillation of chemotherapy during radical cystectomy. Methods: Patients who underwent radical cystectomy for bladder cancer between January 2013 and April 2019 were retrospectively evaluated and divided into a non‐instillation group and an instillation group according to the intraoperative instillation of chemotherapy. Univariate and multivariate Cox regression was used to determine the clinical predictors of overall survival and disease‐free survival. Kaplan–Meier analysis and log‐rank tests were performed to analyze overall survival and disease‐free survival. Results: Of the 320 patients who were enrolled in the study, 113 underwent radical cystectomy with intraoperative instillation of chemotherapy. Univariate Cox analysis showed that intraoperative instillation was not a risk factor for overall survival or disease‐free survival (HR: 1.04, 95% CI: 0.66–1.63, p = 0.864; HR: 1.11, 95% CI: 0.76–1.62, p = 0.602, respectively). As shown in the Kaplan–Meier analysis, no significant differences were noted in overall survival (p = 0.857) and disease‐free survival (p = 0.600) between the two groups. A subgroup analysis demonstrated that intraoperative instillation was not associated with a statistically better overall survival and disease‐free survival in the nonmuscle invasive (p = 0.852 and 0.836) and muscle‐invasive (p = 0.929 and 0.805) patients. Conclusion: A single intraoperative instillation of chemotherapy during radical cystectomy was not related to better disease‐free survival or overall survival. It is unnecessary to consider single instillation of chemotherapy as a regular procedure during radical cystectomy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of pirarubicin intravesical infusion chemotherapy on the expression of serum proliferative invasion genes and tumor related factors in postoperative patients with superficial bladder cancer. Methods: 98 patients with superficial bladder cancer who were admitted to 905 Hospital of the Chinese People's Liberation Army Navy from March 2018 to April 2019 were randomly seleceted, they were divided into control group [treated with transurethral resection of bladder tumor (TURBT)] and study group (treated with intravesical chemotherapy of pirarubicin on the basis of the control group), with 49 cases in each group. The curative effect, serum tumor related factors, expression of proliferation and invasion genes, adverse reaction rate and recurrence rate were compared between the two groups. Results: The total clinical effective rate of the study group was higher than that of the control group (P<0.05). After chemotherapy, the levels of serum vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and matrix metalloproteinase-9 (MMP-9) in the two groups decreased, and the levels in the study group were lower than those in the control group at the same period (P<0.05). After chemotherapy, adenosine triphosphate binding cassette transporter E1 (ABCE1) and nuclear transporter of two groups of proliferating genes α2 (KPNA2), mitochondrial ribosomal protein S5 (MRPS5), invasion gene integrin related kinase (ILK), nuclear factor-kBp65 （NF-k Bp65) decreased, and the study group was lower than the control group in the same period; Invasive gene peroxisome proliferator activated receptorγ（PPARγ ）. It was higher in the study group than in the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups (P>0.05). The recurrence rate in the study group at 1, 2 and 3 years after operation was lower than that in the control group (P<0.05). Conclusion: Pirarubicin intravesical infusion chemotherapy for postoperative patients with superficial bladder cancer can effectively regulate the level of serum tumor related factors and the expression of proliferation and invasion genes, and reduce the recurrence rate of tumor. [ABSTRACT FROM AUTHOR]

Purpose: To show the effect of a 6-month (4 times weekly followed by 5 times monthly) maintenance mitomycin C regimen on the prevention of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods: A total of 119 patients undergoing a RNU between 2007 and 2021 in a single center hospital were retrospectively reviewed. A total of 66 patients were eligible for further analysis. 27 patients received no post-operative MMC (median follow-up: 110 months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48 months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS). Results: There was a significant difference (p = 0.001) in BRFS between the two groups. The 1-, 2, and 5-year BRFS for the MMC− group was 67%, 63% and 43%, respectively. The 1-, 2- and 5-year BRFS for the MMC + group was 95%, 86% and 86%, respectively. Univariate analysis showed no other potential prognostic factors that had a significant effect on the BRFS. Conclusion: A 6-month maintenance schedule of MMC is effective at significantly reducing the risk of IVR after RNU for UTUC. We could not find any other significant prognostic factors to predict IVR. [ABSTRACT FROM AUTHOR]

Purpose of Review: The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. Recent Findings: Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. Summary: As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives. [ABSTRACT FROM AUTHOR]

Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril® Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril® Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p < 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa.

• Immediate postoperative intravesical chemotherapy is underutilized. • No demonstrated risk of complications exists following its use. • Elective surgery and shorter operative times are associated with higher utilization. The use of immediate postoperative intravesical chemotherapy (IVC) following transurethral resection of bladder tumor (TURBT) has been shown to reduce the rate of recurrence of nonmuscle invasive bladder cancer. Historically, utilization of IVC following TURBT has been low. We sought to determine the rate of immediate postoperative IVC following TURBT, as well as assess factors that may influence its use. We utilized the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to assess the rates of IVC between the years 2016 to 2021. All patients who underwent TURBT based on appropriate procedure codes were initially included. Patients with an additional procedure code for the administration of IVC were identified. From 2016 to 2021, 50,295 patients underwent TURBT for bladder cancer. There were 21,544 (43%) small, 18,135 (36%) medium, and 10,616 (21%) large tumors treated. In total, 2,833 (5.6%) patients received IVC. Use of IVC was associated with surgery performed in an elective setting, those who did not receive preoperative blood transfusion, and shorter operative time. Receipt of chemotherapy was more common in the later years examined. The rate of use of IVC remains very low. Ongoing study and improvement initiatives are in place, though these predominantly are assessing academic centers. Further study and quality improvement should be performed and include community practice settings. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens. Objective: To assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient’s risk group. Design, setting, and participants: This economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period. Outcome measurements and statistical analysis: The treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves. Results and limitations: Time to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58–2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06–0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22 959) than for delayed MMC instillation (€24 624), with an adjusted mean difference of −€1350 (95% CI −€1799 to −€900). The study is limited by the retrospective estimation of costs. Conclusions: This trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation. Patient summary: We assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non–muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non–muscle-invasive bladder cancer.

Introduction: The inflammatory response plays a potential role in postoperative recurrence in patients with non-muscular invasive bladder cancer (NMIBC). We aimed to investigate whether platelet-to-lymphocyte ratio (PLR), mean platelet volume to lymphocyte ratio (MPVLR), and the systemic immune-inflammatory index (SII) have prognostic values in NMIBC treated with conventional intravesical chemotherapy or intravesical Chemohyperthermia (CHT) and the differences between them. Materials and methods: A retrospective cohort study was conducted on 222 patients with NMIBC treated with Intravesical Chemotherapy or Intravesical CHT between January 2016 and December 2020. Within a week before surgery, PLR, MPVLR, and SII were determined based on routine blood settling. The optimal cutoff value of each index was determined using the receiver operating characteristic curve, and various groups were categorized accordingly. The factors influencing the prognosis of NMIBC patients receiving various treatments were investigated using the Kaplan-Meier survival curve and the Cox regression model. Results: 69 cases (46.3%) in the gemcitabine (GEM) group had tumor recurrence and 19 (12.8%) of them progressed to muscle-invasive bladder cancer (MIBC) or got metastasis, while 19 cases (26.0%) in the CHT group recurred and 2 (2.7%) progressed. Elevated PLR, MPVLR, and SII were associated with higher recurrence rates in the GEM group. Meanwhile, PLR and MPVLR were the independent risk factors. While in the CHT group, high PLR and SII were related to postoperative recurrence and none of them were independent risk factors. Conclusion: The preoperative clinical inflammatory indexes PLR, SII, and MPVLR have certain predictive value for the postoperative recurrence-free survival (RFS) in NMIBC patients treated with intravesical chemotherapy while PLR and SII can predict the prognosis of NMIBC patients treated with intravesical CHT, which indicates that intravesical CHT may stop tumor recurrence by influencing the effect of mean platelet volume on tumor growth through some unknown mechanisms. [ABSTRACT FROM AUTHOR]

Background: Improving clinical trial design is important for optimizing approval of safe and effective drugs. Phase 1 clinical trials seek to determine phase 2 doses by investigating predefined dose‐limiting toxicities. Traditional definitions of dose‐limiting toxicity may not be applicable to intravesical therapies for bladder cancer. This study compared the frequency of dose‐limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. Methods: Studies were abstracted from ClinicalTrials.gov and reconciled with a PubMed search. Primary and secondary end points were predefined before data abstraction, and the primary end point was subject–level dose‐limiting toxicity rate. Fisher exact tests were performed with p <.05 designated as significant. Results: Eighteen intravesical studies and 24 studies with other routes of administration (the per os/intravenous/intramuscular [PO/IV/IM] group) were identified. Dose‐limiting toxicities were reported in 38.9% of intravesical studies, affecting 3.29% of subjects, compared with 30.0% of PO/IV/IM studies representing 4.19% of subjects (p =.52 for study‐level and p =.60 for subject‐level comparisons). Serious adverse events occurred in 53.9% of intravesical studies in 10.3% of subjects versus 91.0% of studies reporting serious adverse events affecting 41.4% of subjects in the PO/IV/IM group (p =.03 for subject‐level and p <.0001 for study‐level comparisons). Conclusions: There was no difference in subject–level dose‐limiting toxicity rate between intravesical and PO/IV/IM bladder cancer trials. The serious adverse event rate was lower in the intravesical group. Heterogeneity of dose‐limiting toxicity definition may affect interpretation of toxicity in phase 1 bladder cancer clinical trials studying different routes of administration. Lay summary: Bladder cancer is a common cancer type that may be treated with therapies that are instilled into the bladder and act locally, called intravesical therapies.This study used publicly available regulatory data from early phase clinical trials to determine whether measures of tolerability used in clinical trials are applicable to intravesical therapies for bladder cancer. In phase 1 studies, dose‐limiting toxicity may not adequately represent the tolerability of intravesical therapies for bladder cancer. Measures other than dose‐limiting toxicities demonstrate increased tolerability of these therapies compared to therapies with other routes of administration. [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine. A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed. A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h. GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC. [ABSTRACT FROM AUTHOR]

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer., Competing Interests: Declaration of competing interest Siamak Daneshmand has received grants/research funding and travel support from Photocure; consulting/advisory fees from Photocure, Pacific Edge, Ferring, Bristol Myers Squibb, Janssen, Johnson & Johnson, Protara, Urogen, Pfizer, CG Oncology, Vesica Health, and ImmunityBio; and has stock/other ownership interests in Taris. Ashish M. Kamat has served as a consultant for Abbott Molecular, Arquer, ArTara, Asieris, Astra Zeneca, BioClin Therapeutics, Biological Dynamics, Bristol Myers Squibb, Cepheid, Cold Genesys, Eisai, Engene, Ferring, FerGene, Imagin, Incyte DSMB, Janssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara, Roviant, Seattle Genetics, Sessen Bio, Theralase, TMC Innovation, US Biotest, and Urogen; and has contracted research with Adolor, Bristol Myers Squibb, FerGene, FKD Industries, Heat Biologics, Merck, Photocure, and SWOG/NIH and patents with CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center. Neal D. Shore has received grants/research funding from AbbVie, Advantagene, Amgen, Aragon Pharmaceuticals, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clovis Oncology, Dendreon, DisperSol, Endocyte, Exact Imaging, Exelixis, Ferring, FKD Therapies, Forma Therapeutics, Foundation Medicine, Genentech, Guardant Health, InVitae, Istari Oncology, Janssen, Jiansu Yahong Meditech, MDxHealth, Medivation, Merck, MT Group, Myovant Sciences, Myriad, Novartis, Nymox, OncoCellMDx, ORIC Pharmaceuticals, Pacific Edge, Palette Life Sciences, Plexxikon, Pfizer, Point Biopharma, Propella Therapeutics, RhoVac, Sanofi, Seattle Genetics, Sesen Bio, Steba Biotech, Theralase, Tolmar, Urogen, Urotronic, US Biotest, Vaxiion, Veru, and Zenflow; consulting/advisory fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Medicine, Genesis Cancer Care, Genzyme, InVitae, Janssen, Lantheus, Lilly, MDxHealth, Medivation, Myovant Sciences, Myriad Genetics, Nymox, Pacific Edge Biotechnology, Peerview, Pfizer, Phosphorus, Photocure, Propella Therapeutics, Sanofi, Sema4, Sesen Bio, Specialty Networks, Telix Pharmaceuticals, Tempus, Tolmar, Urogen, and Vaxiion; and honoraria/speaker fees from Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Foundation Medicine, Guardant Health, Janssen, Merck, and Pfizer. Joshua J. Meeks has received honoraria from Astellas Pharma, AstraZeneca, Imvax, Incyte, Janssen, Merck, Pfirzer, Prokarium, Urogen Pharma; research funding from Epizyme and Merck Sharp & Dohme; has patents, royalties, or other intellectual property (institutional) : NMIBC classifier, TCGA classifier; and has a relationship (undefined) with Olympus. Matthew D. Galsky has served as a consultant for Abbvie Inc, Alligator, Astellas Pharma, AstraZeneca, Basilea, Bicycle, Bristol Myers Squibb, Curis, Dracen, Dragonfly, EMD Serono, FujiFilm Holdings America Corporation, Genentech, Gilead Sciences, GlaxoSmithKline, Incyte Corp, Janssen Biotech, Merck, Numab, Pfizer, Rappta Therapeutics, Seattle Genetics, and Veracyte. Joseph M. Jacob has received consulting or advisory fees from Janssen, Photocure, Urogen, and Verity Pharmaceuticals. Michiel S. van der Heijden has served as a consultant (paid to institution) for Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, MSD Oncology, Pfizer, Roche, and Seagen; and has received institutional research funding from 4SC, AstraZeneca, Bristol Myers Squibb, and Roche. Stephen B. Williams has no disclosures to report. Thomas Powles has received consulting fees from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mash Up Ltd, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; grant support from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Seattle Genetics, and Roche; and support for attending meetings and/or travel from AstraZeneca, Ipsen, MSD, Pfizer, and Roche. Sam S. Chang has served as a consultant for ImmunityBio, Janssen, Merck, Pfizer, and Uro Urogen; Vanderbilt University Medical Center is a trial site for TAR-200. James W. F. Catto has received honoraria from AstraZeneca, Bristol Myers Squibb, and Roche; consultant fees from AstraZeneca, Bristol Myers Squibb, Ferring, Gilead Sciences, Ipsen, Janssen, QED Therapeutics, Photocure, Roche, and Steba Biotech; and institutional grants from Roche; has participated in a data safety monitoring board or advisory board for Bristol Myers Squibb; and is an unpaid trustee for Fight Bladder Cancer UK and Weston Park Cancer Charity. Sarah P. Psutka has had a consulting or advisory role with Janssen, Medtronic, and Merck; and has received honoraria from AstraZeneca. Félix Guerrero-Ramos has received grants/research funding from Combat Medical; consulting/advisory fees from AstraZeneca, Bristol Myers Squibb, Combat Medical, and Janssen; honoraria/speaker fees from Combat Medical, Janssen, and Pfizer; and travel support from Ipsen and Pfizer. Evanguelos Xylinas has received grants/research funding from Ferring; and consulting/advisory fees from Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, and Bristol Myers Squibb. Makito Miyake has no disclosures to report. Giuseppe Simone has no disclosures to report. Karen Daniel, Hussein Sweiti, and Christopher Cutie are employees of Janssen Research & Development and may have stock/stock options with Johnson & Johnson. Andrea Necchi has served as a consultant or advisor for Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Incyte, Janssen, Merck, Pfizer, and Roche; and has received institutional grant support from Bristol Myers Squibb, Gilead Sciences, and Merck., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy occurs in 22% to 47%. Intravesical chemotherapy is still underused due to concerns about its efficacy and safety. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of intravesical chemotherapy regimens in reducing the risk of intravesical recurrence following radical nephroureterectomy., Materials and Methods: A literature search was conducted using PubMed/Medline, Embase, and Web of Science databases to identify reports published until March 2024. The PRISMA guidelines were followed to identify eligible studies. The outcomes measured were intravesical recurrence rates and complications in patients treated with different intravesical instillation chemotherapy and timing after radical nephroureterectomy. Sub-analyses were performed on randomized controlled trials and studies involving patients with no history of bladder cancer., Results: Eighteen studies met our inclusion criteria, and data from 2,483 patients were reviewed. Intravesical chemotherapy significantly reduced the risk of intravesical recurrence at 12 months (OR = 0.46; 95% CI: 0.33-0.65; P < 0.001;) and at 24 months (OR = 0.41, 95% CI: 0.28-0.61; P < 0.001). Notably, no association was found when confronting intra and postoperative instillations (OR = 0.66; 95% CI: 0.34-1.28; P = 0.2), nor single vs. multiple instillation (OR = 1.37; 95% CI: 0.75-2.50; P = 0.3). The pooled rate for minor and major complications was 9% and 0.9%, respectively., Conclusion: This study demonstrates that intravesical chemotherapy significantly reduces intravesical recurrence rates after radical nephroureterectomy at 12 and 24 months. Additionally, it underscores the favorable safety profile of intravesical chemotherapy, with a low incidence of major complications. The ideal instillation scheme and chemotherapy agent should be further defined., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Development of therapeutic strategies for non-muscle-invasive bladder cancer (NMIBC) that failed intravesical Bacillus Calmette - Guerin (BCG) therapy remains an urgent priority for clinicians. Currently, radical cystectomy is the recommended standard of care treatment options for these patients. Intravesical chemotherapy using gemcitabine and docetaxel are regarded as the most effective treatment options for unresponsive NMIBC, however, these options are ineffective in the control of bladder cancer. In this review, we present the definition of BCG unresponsive NMIBC and discuss about the recent management options that include immunotherapy, intravesical chemotherapy, gene therapy, and targeted individualized therapy. Notably, immunotherapy is the most recent strategy utilizing the PD-1/PD-L1 and other immune checkpoint inhibitors (ICIs). Pembrolizumab (KEYNOTE-057), Atezolizumab (SWOG S1605) and Nivolumab were developed and are efficacious in BCG –unresponsive NMIBC. In summary, ICIs are considered as the most promising agent for BCG unresponsive NMIBC in the future.

Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril® Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril® Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p < 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the tolerability of postoperative early intravesical chemotherapy session after transurethral resection of the bladder tumor (TUR-B) according to the different anesthesia types. Methods: The study was conducted between February 2017 and June 2020. Patients who were given intravesical mitomycin (MMC) 40 mg after TUR-B were included. Patients' risk categories (low, medium, and high) were determined according to the European Association of Urology (EAU) risk stratification system based on the tumor number, size (<3 and ≥3 cm), T stage (Ta and T1), and grade (low and high). Patients were divided into 2 groups according to the applied anesthesia technique as group S (spinal) and group G (general). The patients' visual analog scale (VAS) scores were recorded every 30 min for 2 h after urethral clamping. The patients' pain scores were recorded using the VAS questionnaire form at 30th (VAS1), 60th (VAS2), 90th (VAS3), and 120th (VAS4) min after the urethral clamping. Requirement of analgesic, urethral clamp removal time, total instillation time, and discharged urine volume were recorded. Complications and complication grade (1–5) were recorded according to the Clavien-Dindo system. Results: A total of 232 consecutive patients who received intravesical MMC were included. Sociodemographic characteristics of group S (n = 113) and group G (n = 119) were similar (p < 0.05). There were no significant differences in tumor size, number of tumors, concomitant CIS, and T stage in both groups (p > 0.05). High-grade tumors were higher in group S (23.9 vs. 11%; p = 0.008). Requirement of analgesic (53.9 vs. 91.5%; p = 0.00) and termination of therapy <60′ (2 vs. 26%; p = 0.00) and <120′ (32.7 vs. 76.4%; p = 0.00) were significantly lower in group S. The mean instillation time (108.05 ± 19.40 vs. 85.67 ± 24.66 min; p = 0.00) was found significantly higher for group S. In group G, mean VAS1–4 scores were significantly higher than in group S (p < 0.05). Linear correlation analyses showed that the VAS score is correlated with the instillation time (p < 0.05). The rates of minor (I–III) (7 vs. 8%; p = 0.706) and major (IV–V) (0.9 vs. 1.6%; p = 0.590) complications were similar in both groups. Conclusion: The patients' tolerability of intravesical MMC treatment can be improved by spinal anesthesia. It provides longer instillation time and less pain during intravesical chemotherapy. [ABSTRACT FROM AUTHOR]

Aim: Bladder cancer is the second most common urological malignancy after prostate cancer. Increase in the post-void residual (PVR) volume may result in an increase in the risk of cancer recurrence. Methods: Patient demographic data, tumor stage and grade, PVR volume and 2 years follow-up data for recurrence were obtained and evaluated. Results: One-hundred-and-nineteen patients were subdivided into three groups according to PVR urine volume. The increase of PVR volume was related to short recurrence-free survival (RFS) especially for patients with PVR volume of 60 ml or more. Conclusion: Low PVR volume in patients with non-muscle invasive bladder cancer may play a role in reducing cancer recurrence. However further research is needed in this field.

Copyright of Urologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bladder cancer is one of the most common malignant tumors in urinary system. Intravesical chemotherapy is a common adjuvant therapy after transurethral resection of bladder tumors. However, it has several disadvantages such as low drug penetration rate, short residence time, unsustainable action and inability to release slowly, thus new drug delivery and new modalities in delivery carriers need to be continuously explored. Nano-drug delivery system is a novel way in treatment for bladder cancer that can increase the absorption rate and prolong the duration of drug, as well as sustain the action by controlling drug release. Currently, nano-drug delivery carriers mainly included liposomes, polymers, and inorganic materials. In this paper, we reveal current researches in nano-drug delivery system in bladder cancer intravesical chemotherapy by describing the applications and defects of liposomes, polymers and inorganic material nanocarriers, and provide a basis for the improvement of intravesical chemotherapy drugs in bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Kidney-sparing surgery (KSS) for upper tract urothelial carcinomas (UTUCs) has been gradually performed in selected patients beyond the recommendation of guidelines. However, there is still a lack of tools to evaluate postoperative local recurrence. Herein, a new nomogram was established to predict the local recurrence risk after KSS. Methods: Patients were randomly divided into two cohorts (training: testing cohorts = 7:3). Cancer samples after KSS were used for immunohistochemical tests to detect molecules missing in previous pathology reports. Then, the total number of molecules were screened by the least absolute shrinkage and selection operator (LASSO) method to construct an IHCscore, which was further tested in the validation cohort. Finally, the IHCscore and other clinicopathologic parameters were combined to develop a more accurate model using univariate and multivariate Cox regression methods. Results: In total, 200 patients were included. The Kaplan–Meier test showed that high Ki-67 and loss of Uroplakin III and E-cadherin were correlated with poor recurrence-free survival. The individual IHCscore was calculated based on the expression levels of Ki-67, Her2 and E-cadherin. Based on the IHC score, patients were further classified as low- or high-risk, and a significant difference in the recurrence-free survival was observed between the two groups. Then, the nomogram was developed based on Gender, surgical margin and IHCscore; this nomogram had a higher AUC (0.847) in predicting 3-year recurrence-free survival than the IHCscore alone (0.788). Conclusions: This easy-to-use nomogram shows better prediction accuracy in recurrence-free survival after KSS and may guide individualized intravesical chemotherapy. However, a larger sample is required for external validation. [ABSTRACT FROM AUTHOR]

Bladder cancer is a heterogeneous disease with variable natural history. Non-muscle-invasive bladder cancer has a favorable prognosis following transurethral resection, but the optimal adjuvant chemotherapy plan is still in debate. The aim of this study was to evaluate the effect of the adjuvant intravesical administration of a single dose of gemcitabine in the outcome of this disease. For that purpose, we performed a systematic review and meta-analysis on available randomized control trials on MEDLINE, EMBASE, Cochrane, Scopus, and Google Scholar databases. Ultimately, two studies were included with a total number of 654 patients. The statistical analysis performed showed that a single post-operative intravesical dose of gemcitabine does not affect the recurrence rate of non-muscle-invasive bladder cancer compared to placebo. Therefore, this therapeutic strategy does not offer any significant improvement on the outcomes of the disease. Nonetheless, due to the plethora of available therapeutic agents and treatment strategies, further research is needed to establish the optimal treatment in this category of patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) and intravesical chemotherapy (IVEC) in patients with intermediate and high risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection. Methods: We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers. We matched 364 intermediate or high risk cases and divided them into 2 groups: the HIVEC+IVEC group [chemohyperthermia (CHT) composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia] and the IVEC group (intravesical instillation without hyperthermia). The data were recorded in the database. The primary endpoint was 2-year recurrence-free survival (RFS) in all NMIBC patients (n = 364), whereas the secondary endpoints were the assessment of radical cystectomy (RC) and 5-year overall survival (OS). Results: There was a significant difference in the 2-year RFS between the two groups in all patients (n = 364; HIVEC+IVEC: 82.42% vs. IVEC: 74.18%, P = 0.038). Compared with the IVEC group, the HIVEC+IVEC group had a lower incidence of RC (P = 0.0274). However, the 5-year OS was the same between the 2 groups (P = 0.1434). Adverse events (AEs) occurred in 32.7% of all patients, but none of the events was serious (grades 3–4). No difference in the incidence or severity of AEs between each treatment modality was observed. Conclusions: This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients. Both treatments were well-tolerated in a similar manner.

BackgroundKidney-sparing surgery (KSS) for upper tract urothelial carcinomas (UTUCs) has been gradually performed in selected patients beyond the recommendation of guidelines. However, there is still a lack of tools to evaluate postoperative local recurrence. Herein, a new nomogram was established to predict the local recurrence risk after KSS.MethodsPatients were randomly divided into two cohorts (training: testing cohorts = 7:3). Cancer samples after KSS were used for immunohistochemical tests to detect molecules missing in previous pathology reports. Then, the total number of molecules were screened by the least absolute shrinkage and selection operator (LASSO) method to construct an IHCscore, which was further tested in the validation cohort. Finally, the IHCscore and other clinicopathologic parameters were combined to develop a more accurate model using univariate and multivariate Cox regression methods.ResultsIn total, 200 patients were included. The Kaplan–Meier test showed that high Ki-67 and loss of Uroplakin III and E-cadherin were correlated with poor recurrence-free survival. The individual IHCscore was calculated based on the expression levels of Ki-67, Her2 and E-cadherin. Based on the IHC score, patients were further classified as low- or high-risk, and a significant difference in the recurrence-free survival was observed between the two groups. Then, the nomogram was developed based on Gender, surgical margin and IHCscore; this nomogram had a higher AUC (0.847) in predicting 3-year recurrence-free survival than the IHCscore alone (0.788).ConclusionsThis easy-to-use nomogram shows better prediction accuracy in recurrence-free survival after KSS and may guide individualized intravesical chemotherapy. However, a larger sample is required for external validation.