Intravesical Therapy Research Articles

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer.

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. 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. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

Efficacy of outpatient surveillance in post-intravesical BCG management of high-risk bladder cancer

Background: Intravesical Bacillus Calmette–Guérin (BCG) instillation is an established form of immunotherapy for intermediate and high-risk bladder cancers. Mandatory cystoscopic surveillance is commonly performed under general anaesthesia (GA) to facilitate biopsy or other procedures. However, it is resource-intensive with unclear clinical benefit. Methods and patients: We performed a two-cycle audit, before and after changing post-BCG surveillance policy, from GA cystoscopy to local anaesthetic flexible cystoscopy (LAFC) on trans urethral laser ablation (TULA) lists, where patients may undergo a tumour biopsy or laser ablation. In the first cycle, we audited 53 patients undergoing 114 post-BCG rigid cystoscopies from January 2018 to December 2019. In the second cycle, there were 56 patients undergoing 99 post-BCG LAFCs on TULA lists in 2020. Results: In the first audit cycle cohort, the mean patient age was 72.29 ± 8.98 years and 48 were men; malignant histology was identified only on five occasions (three grade progressions). Fourteen patients required overnight admission. In the second audit cycle cohort, the mean patient age was 70.44 ± 9.17 years and 47 were men. Four had a grade progression, while another a stage progression. Out of 99 LAFCs, 47 confirmed normal bladder appearance. A biopsy was taken during other 52 cystoscopies: 17 (33%) confirmed malignancy. Fifteen patients showed findings that were labelled as recurrence, but only two required a further GA procedure to deal with recurrence. One patient was admitted for post-procedure bleeding, which settled with irrigation. Conclusion: Local anaesthetic TULA procedure is a safe and effective alternative for a GA rigid cystoscopy to survey bladders of patients on intravesical BCG therapy. Level of evidence: 3

Systematic review and meta-analysis of ketamine-associated uropathy.

This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management. A literature search was conducted using keywords and MeSH terms related to ketamine abuse, urinary tracts, and urological examinations. Databases including Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched up to 26 June 2020. In total, 1365 articles were retrieved; 45 articles (4921 patients) were included in the analysis of patient demographics, clinical manifestations, examination results, and treatments. Frequency was the most common manifestation (pooled prevalence 77.1%, 95% confidence interval [CI]=56.9%-92.2%), followed by urgency (69.9%, 95% CI=48.8%-87.3%) and suprapubic pain (60.4%, 95% CI=35.3%-82.9%). Upper urinary tract involvement was less common; the pooled prevalence of hydronephrosis was 30.2% (95% CI=22.0%-39.2%). Further workup revealed a pooled functional bladder capacity of 95.23 mL (95% CI=63.57-126.88 mL), pooled voided volume of 113.31 mL (95% CI=59.44- 167.19 mL), and pooled maximum urine flow rate of 8.69 mL/s (95% CI=5.54-11.83 mL/s). Cystoscopic examinations and bladder biopsy revealed frequent urothelial denudation, inflammatory changes, and inflammatory cell infiltration. Treatments included oral medications for symptomatic relief, intravesical therapy, and surgery (eg, hydrodistension and bladder reconstruction), but ketamine abstinence was necessary for improvement. Ketamine-associated uropathy frequently involves frequency, urgency, and suprapubic pain; upper urinary tract involvement is less common. Affected patients showed reductions in bladder capacity and urine flow rate. Endoscopic and histological analyses often revealed cystitis. Despite variations in treatment, ketamine abstinence is important for all patients with ketamine-associated uropathy.

Intravesical Therapy Compared to Radical Cystectomy Among Patients With Non-Muscle Invasive Bladder Cancer Requiring Additional Treatment After Induction BCG.

Many patients with recurrent high-risk non-muscle invasive bladder cancer after intravesical bacillus calmette-guerin (BCG) face a difficult decision between radical cystectomy (RC) or salvage intravesical therapy (IVT). We sought to determine if there is a difference in overall survival RC and IVT after previous treatment with BCG. We performed a retrospective cohort study of patients with Ta, T1, and Tis bladder cancer treated with induction BCG in the SEER-Medicare dataset from 2000 to 2015. We used a proportional hazards regression model to compare differences in survival between patients having RC and IVT. We adjusted for confounding using a propensity score and stratified our analysis according to timing of treatment and stage at diagnosis. We identified 3940 patients who received either IVT (79%) or RC (21%) following induction BCG. Among patients treated within 12 months of BCG, there was no significant difference in survival between RC and IVT (HR 0.92, 95% CI 0.81-1.04) and 17% of patients having early IVT ultimately required RC. Among patients treated at least 12 months after BCG, RC was associated with worse survival than IVT (HR 1.19, 95% CI 1.06-1.35) and 10% of patients having late IVT ultimately required RC. Among patients with bladder cancer who required additional treatments after induction BCG, we did not observe a difference in overall survival between IVT and RC within 12 months of starting BCG. While RC remains the gold-standard for high risk recurrent NMIBC after BCG, bladder preservation with IVT may be appropriate for well-selected patients.

Analysis of sex-based differences to Bacillus Calmette-Guérin for non-muscle invasive bladder cancer.

To evaluate whether differences exist between men and women in response to intravesical BCG treatments. The incidence of urothelial carcinoma of the bladder is lower in women but they tend to present with more aggressive and advanced disease. Some prior studies also suggest there are sex-based differences in response to treatment for non-muscle invasive bladder tumors. In this retrospective study, we reviewed all consecutive patients who received BCG at the CHU de Québec - Laval University from 2009-2019. Men and women were treated with intravesical BCG therapy following pathologic confirmation of urothelial carcinoma. Outcomes evaluated include recurrence, progression, and treatment tolerability. Recurrence was defined as a pathology confirmed cancer whereas progression was the new development of high-grade (recurrence) pathology or an increase of stage. Tolerability was defined according to the proportion of prescribed BCG received. All clinical details were obtained through review of the medical records, collaborated by pharmacy records for BCG administration. Competing-risk analysis was used to compare outcomes. Among 613 patients who received BCG at our institution between 2009-2019, 472 (77.0%) were men and 141 (23.0%) were women. The recurrence rate was not different between sexes, with a 5-year recurrence risk of 52% (95% CI: 36.93-65.4) among women compared to 57.5% (CI 95%: 51.9-62.6) among men. The overall non-progression rate at 1,3 and 5 years was 97.3% (95% CI: 95.6%-98.3%), 93.6% (95% CI: 91.2%-95.4%), and 91.7% (95% CI: 88.4%-94.1%), respectively. The completion of ≥5 induction BCG instillations and maintenance BCG use was similar in both genders. We report a contemporary NMIBC cohort treated with BCG and find no clear evidence for sex-based differences in response to BCG treatment in regard of progression, recurrence, and tolerability.

Effects of acupuncture to decrease adverse events in patients with high-risk non-muscle invasive bladder cancer receiving induction intravesical BCG therapy: Study protocol for a randomized, controlled pilot and feasibility study

BackgroundTreatment-related serious adverse events (SAEs) are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC). Here we describe the protocol of a randomized, attention/waitlist-controlled feasibility pilot study testing the use of acupuncture to decrease SAEs and treatment interruptions in this population. The primary objectives are to evaluate the feasibility and efficacy of conducting pre-procedure acupuncture in a Urology Clinic. MethodsA total of 45 patients will be recruited and randomized in a 2:1 ratio (treatment arm: attention/waitlist control). Eligibility criteria include 1) age 18 years or older, 2) English-speaking, 3) high-risk NMIBC, 4) no acupuncture in the previous 3 months, and 5) willing and able to participate in trial activities. Patients in the treatment arm will receive acupuncture prior to weekly BCG for a total of six weeks. Methods were developed to train and monitor research acupuncturists and included online and in-person training, study manuals, and monthly meetings throughout the study period. Feasibility assessments include evaluation of the recruitment, retention and protocol adherence to acupuncture treatment, and measurement of CTCAE v5.0 adverse events specific to acupuncture, and clinic staff surveys regarding the intervention impact on clinic workflow. Efficacy measures will be compared between treatment and control groups including: EORTC-QLQ-NMIBC-24, EORTC-QLQ-C30, CTCAE v5.0, medication journal, healthcare utilization, current use of complementary, alternative, and integrative therapies, and acupuncture expectancy and treatment preference. Trial results will inform the design of a multi-center trial to expand testing of the protocol to a larger patient cohort.

Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).

The efficacy and safety of intravesical chondroitin sulphate solution in recurrent urinary tract infections

BackgroundUrinary tract infections are among the most common indications for antibiotic therapy. The emergence of resistant uropathogens indicates the need for treatment alternatives. Replenishment of the glycosaminoglycan layer of the bladder, achieved by intravesical instillation of e.g. chondroitin sulphate (CS), is described to be a cornerstone in the therapy of cystitis. To retrospectively evaluate the efficacy of a therapy with 0.2% CS in patients suffering recurrent urinary tract infections (rUTI) in comparison to a treatment with low-dose long-term antibiotics (LDLTAB) and a combination of both.MethodsA total of 151 patients with recurrent UTI who underwent intravesical therapy at Diaconesse hospital in Leiden, The Netherlands were included. 50 patients had been treated with CS, 51 patients had received LDLTAB, and 50 patients had received a combination therapy (LDLTABCS). Data recorded for baseline, after 6, and 12 months of treatment were evaluated. Descriptive statistics were calculated. Exploratory comparisons between groups and within groups were performed by using one-tailed and paired t-tests. Patients filled in a standardized quality of life questionnaire (EQ-5D).ResultsWe found a statistically significant reduction of number of infections from 7.10 ± 0.50 SEM to 0.45 ± 0.07 SEM after 12 months therapy with CS compared to 12 months therapy with LDLTAB (from 7.04 ± 0.47 SEM to 1.8 ± 0.15 SEM). The number of visits to the urologist significantly decreased in the CS group from 7.46 ± 0.80 SEM to 1.28 ± 0.11 SEM and from 4.10 ± 0.29 SEM to 1.35 ± 0.11 SEM in the LDLTABCS group. In addition, a significant increase in Quality of life (QoL) was seen in the CS-group (from 58.2 ± 0.82 SEM to 80.43 ± 0.82 SEM) and in the LDLTABCS group (from 62.4 ± 0.97 SEM to 76.73 ± 1.06 SEM). There was no improvement in QoL with LDLTAB (from 58.24 ± 1.08 SEM to 58.96 ± 1.19 SEM). Evaluation’s evidence is limited due to its retrospective character.ConclusionsRetrospective analysis of data from patients that underwent therapy for rUTIs confirms the safety and efficacy of CS and indicate a superiority to antibiotic treatment of rUTIs.

The use of natural killer cell activity and PPD test in the prediction of results in intravesical BCG treatment of patients with nonmuscle-invasive bladder cancer.

To predict the efficacy of intravesical BCG therapy in patients with nonmuscle-invasive bladder tumors (NIBC) by using components of the cellular immune response such as the tuberculin skin test (PPD) and natural killer (NK) activity measurement. Ninety-nine patients who were started on intravesical BCG therapy for NIBC were evaluated prospectively. Patients who were included in the intermediate, high, and very high-risk groups according to the EAU NMIBC Scoring System and who had never received intravesical BCG therapy previously were included. The clinical and demographic characteristics of the patients (age, gender, EAU NMBIC risk group, EORTC progression and recurrence scores, CUETO progression and recurrence scores, presence and types of comorbidity) were recorded. NK activity was measured and the PPD test was applied 3days before the start of intravesical BCG therapy. The results of PPD were measured in millimeters 72h after the test. PPD values measured before BCG treatment, as an independent variable, were found to be significantly lower in patients with recurrence. A significant correlation was detected between NK activity results obtained before BCG treatment and recurrence after treatment, when the cutoff was 200-500pg/dl. There was no significant relationship between the time to recurrence and PPD and NKA measurements. We conclude that the results of PPD test and NK activity measurement performed before starting intravesical BCG therapy in NIBC may be a marker that can be used to predict the risk of recurrence under treatment.

Translocation of nuclear chromatin distribution to the periphery reflects dephosphorylated threonine-821/826 of the retinoblastoma protein (pRb) in T24 cells treated with Bacillus Calmette-Guérin.

The standard treatment for non-muscle-invasive bladder cancer is intravesical Bacillus Calmette-Guérin (BCG) therapy, which is considered the only intravesical therapy that reduces the risk of progression to muscle-invasive cancer. BCG unresponsiveness, in which intravesical BCG therapy is ineffective, has become a problem. It is thus important to evaluate the effectiveness of BCG treatment for patients as soon as possible in order to identify the optimal therapy. Urine cytology is a noninvasive, easy, and cost-effective method that has been used during BCG treatment, but primarily only to determine benign or malignant status; findings concerning the efficacy of BCG treatment based on urine cytology have not been reported. We investigated the relationship between BCG exposure and nuclear an important criterion in urine cytology, i.e., nuclear chromatin patterns. We used three types of cultured cells to evaluate nuclear chromatin patterns and the cell cycle, and we used T24 cells to evaluate the phosphorylation of retinoblastoma protein (pRb) in six-times of BCG exposures. The results revealed that after the second BCG exposure, (i) nuclear chromatin is distributed predominantly at the nuclear periphery and (ii) the dephosphorylation of threonine-821/826 in pRb occurs. This is the first report of a dynamic change in the nuclear chromatin pattern induced by exposure to BCG. Molecular findings also suggested a relationship between this phenomenon and cell-cycle proteins. Although these results are preliminary, they contribute to our understanding of the cytomorphological changes that occur with BCG exposure.

LogP of N-acyl-gemcitabine and lectin-corona emerge as key parameters in nanoparticulate intravesical cancer therapy

After surgical removal of the tumour tissue, bladder cancer is treated by intravesical instillation of cytotoxic drugs such as gemcitabine. Gemcitabine, however, is highly hydrophilic and possesses a short half-life due to fast enzymatic deamination. Additionally, continuous dilution by urine, a hardly permeable urothelial barrier and rapid excretion by urination make therapy difficult. To modify lipophilicity of the drug, N-acyl-gemcitabine derivatives with quite different solubility and logP were synthesized, purified and characterized. The loading of PLGA nanoparticles with the N-acyl-gemcitabine derivatives followed by release in artificial urine, revealed that the drug content increases but the subsequent release decreases with lipophilicity. Additionally, acylation increased cytotoxicity and opened passive diffusion as an additional pathway into cancer cells. To address physiological constraints, the surface of the monodisperse nanoparticles was grafted with bioadhesive wheat germ agglutinin. Cytoadhesion to artificial bladder cancer tissue and even uptake into the cells as indicated by microscopic imaging are expected to prolong the retention time in the bladder cavity as well as to promote uptake into the cells. By using N-caprylic-gemcitabine as most appropriate gemcitabine-derivative for drug loading and making use of the bioadhesive characteristics of wheat germ agglutinin for grafting the corona of PLGA-nanoparticles, an innovative strategy towards smart drug delivery for instillative therapy of bladder cancer is proposed.

Preliminary efficacy of [90Y]DOTA-biotin-avidin radiotherapy against non-muscle invasive bladder cancer.

Bladder cancer represents 3% of all new cancer diagnoses per year. We propose intravesical radionuclide therapy using the β-emitter 90Y linked to DOTA-biotin-avidin ([90Y]DBA) to deliver short-range radiation against non-muscle invasive bladder cancer (NMIBC). Image-guided biodistribution of intravesical DBA was investigated in an animal model by radiolabeling DBA with the 68Ga and dynamic microPET imaging following intravesical infusion of [68Ga]DBA for up to 4h and post-necropsy γ-counting of organs. The antitumor activity of [90Y]DBA was investigated using an orthotopic MB49 murine bladder cancer model. Mice were injected with luciferase-expressing MB49 cells and treated via intravesical administration with 9.2MBq of [90Y]DBA or unlabeled DBA 3days after the tumor implantation. Bioluminescence imaging was conducted after tumor implantation to monitor the bladder tumor growth. In addition, we investigated the effects of [90Y]DBA radiation on urothelial histology with immunohistochemistry analysis of bladder morphology. Our results demonstrated that DBA is contained in the bladder for up to 4h after intravesical infusion. A single dose of [90Y]DBA radiation treatment significantly reduced growth of MB49 bladder carcinoma. Attaching 90Y-DOTA-biotin to avidin prevents its re-absorption into the blood and distribution throughout the rest of the body. Furthermore, immunohistochemistry demonstrated that [90Y]DBA radiation treatment did not cause short-term damage to urotheliumat day 10, which appeared similar to the normal urothelium of healthy mice. Our data demonstrates the potential of intravesical [90Y]DBA as a treatment for non-muscle invasive bladder cancer.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin

Introduction and objectivesAlthough the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. Patients and methodsA retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. ResultsAsymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation. ConclusionsGenitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

P139 - Results of phase I dose escalation of the trifunctional anti-EpCAM/CD3 bsAb Catumaxomab in intravesical therapy of high risk non muscle invasive bladder cancer (HR-NMIBC): Excellent tolerability and encouraging preliminary efficacy

P139 - Results of phase I dose escalation of the trifunctional anti-EpCAM/CD3 bsAb Catumaxomab in intravesical therapy of high risk non muscle invasive bladder cancer (HR-NMIBC): Excellent tolerability and encouraging preliminary efficacy

Evaluation of toxicities for intravesical drugs in phase 1 bladder cancer trials.

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. 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. 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). 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. 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.

Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introduction and objectivesAlthough the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. Patients and methodsA retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. ResultsAsymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. ConclusionsGenitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Real-world treatment patterns among patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin (BCG).

404 Background: Intravesical BCG is a common treatment in high-risk NMIBC patients; however supply constraints and regimen demands for patients have been reported and may impact long term patient outcomes. This study examined treatment patterns in NMIBC patients receiving intravesical BCG. Methods: Adults with NMIBC treated with intravesical BCG during any line of therapy (LOT) on or after the index date (first date for transurethral resection of the bladder tumor [TURBT] or initiation of intravesical therapy) were selected from de-identified IBM MarketScan Commercial and Medicare Supplemental Databases (1/1/2010-2/28/2021) and Multi-State Medicaid Database (1/1/2010-12/31/2019). Classification of NMIBC on the index date required that patients have no prior systemic antineoplastic therapy, radiotherapy, or cystectomy. Treatment patterns were evaluated from the index date until the end of the NMIBC phase (earliest of initiation of systemic antineoplastic therapy, cystectomy, radiotherapy, diagnosis for metastatic cancer, end of insurance eligibility, or end of data availability). Discontinuation of a LOT was defined as having a treatment gap &gt; 180 days for BCG (90 days for other agents) or switching to a new LOT. During each LOT, adequate BCG treatment was defined as having ≥5 claims during induction (first 42 days of treatment) and ≥2 claims during maintenance (beyond the first 42 days). Results: There were 5,410 NMIBC patients treated with BCG over a mean (median) follow up of 25.5 (18.9) months. The population was 79% male; mean age was 67 years. The majority of patients only received a single LOT (76%; TABLE). The predominant first LOT was BCG (93.1% of NMIBC patients); however, the majority (69.8%) did not receive adequate BCG induction/maintenance in first LOT. Nearly half (46.4%) of first LOT patients had reassessment for disease progression by TURBT. BCG retreatment after a six-month lapse was observed as the predominant second LOT, with &gt; 90% receiving inadequate BCG induction/maintenance. Conclusions: While intravesical BCG remains the most common therapy for NMIBC, less than a third of patients receive adequate BCG treatment in the first LOT; with this percentage further decreasing in the few patients who receive a subsequent LOT. In light of supply and demand constraints, results of this study further emphasize a need for additional treatment options that are effective, safe, and tolerable for patients with NMIBC.[Table: see text]

Muscular pseudotumor revealing a mycobacterial granuloma after bacillus Calmette-Guérin therapy

IntroductionThe Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis. Intravesical therapy with BCG has long been proved to be effective in treating early-stage bladder carcinoma. Case reportA 81-year-old male patient with former history of BCG instillations for bladder cancer two years ago was admitted in February 2020 to our department for a pulsatile and painful tumefaction of the right thigh that lasted for 6 months, due to a muscular M. bovis granuloma leading to femoral artery erosion. Emergency vascular surgery associated with prolonged antibiotherapy provided full recovery. DiscussionLate infectious complications of intravesical BCG instillations are classical but rare. Isolated muscular involvement is exceptional. ConclusionMycobacterial infection should be carefully screened face to a granuloma presenting as muscular pseudotumor. A history of BCG therapy, even decades earlier, enhances this hypothesis and should lead to enforce microbiological testing, especially molecular test.

Mucoadhesive Polymers and Their Applications in Drug Delivery Systems for the Treatment of Bladder Cancer

Bladder cancer (BC) is the tenth most common type of cancer worldwide, affecting up to four times more men than women. Depending on the stage of the tumor, different therapy protocols are applied. Non-muscle-invasive cancer englobes around 70% of the cases and is usually treated using the transurethral resection of bladder tumor (TURBIT) followed by the instillation of chemotherapy or immunotherapy. However, due to bladder anatomy and physiology, current intravesical therapies present limitations concerning permeation and time of residence. Furthermore, they require several frequent catheter insertions with a reduced interval between doses, which is highly demotivating for the patient. This scenario has encouraged several pieces of research focusing on the development of drug delivery systems (DDS) to improve drug time residence, permeation capacity, and target release. In this review, the current situation of BC is described concerning the disease and available treatments, followed by a report on the main DDS developed in the past few years, focusing on those based on mucoadhesive polymers as a strategy. A brief review of methods to evaluate mucoadhesion properties is also presented; lastly, different polymers suitable for this application are discussed.

Intra-Diverticular Bladder Tumours: How to Manage Rationally

Objective To report changing practice in the management of intra-diverticular bladder tumours. Methods We undertook a review of all intra-diverticular bladder tumours in our prospectively maintained institutional database. Results A total of 28 patients (male = 27, female = 1) with a median age of 71 years (IQR 61 to 76) were diagnosed with intra-diverticular bladder tumours (IDBT) between March 2013 and February 2021. Fourteen had visible and 3 had non-visible haematuria, while 11 patients had lower urinary tract symptoms. Median axial diameter of the diverticula was 46 mm (IQR 35 to 69), and median neck diameter was 9 mm (IQR 7 to 11). All patients had CT-urography and 5 patients also had an MRI. Surgical treatment consisted of diverticulectomy (n = 11), diverticulectomy and ipsilateral ureteric reimplantation (n = 11), radical cystectomy and ileal conduit (n = 4), or radical cystectomy and orthotopic bladder (n = 2). Eleven patients had open procedures, and 17 had robotic assisted surgery. Final pathological stages were T0 (n = 2), Ta (n = 5), T1 (n = 7), T3a (n = 8) and T3b (n = 6). Twenty-four patients had urothelial carcinoma (including one nested variant and 4 with squamous differentiation) and 2 had small cell carcinoma. Three patients had neoadjuvant systemic chemotherapy, 2 had intravesical bacillus Calmette-Guerin (BCG) with mitomycin, and one had BCG monotherapy preoperatively. Five patients had adjuvant systemic chemotherapy while 7 had adjuvant intravesical therapies. Mean follow-up period was 37.8 months (±25.3). Mean recurrence-free survival was 61.5% (CI 45.7 to 77.4) and mean overall survival 71.6 % (CI 57.4 to 85.8). Ten patients (37%) died of cancer. Conclusion Management of intra-diverticular bladder tumours is evolving. Bladder-sparing approaches are gaining popularity. Robot-assisted diverticulectomy is preferable as it reduces the morbidity resulting from treatment.