High-grade Non-muscle Invasive Bladder Research Articles

Management of T1G3 Transitional Cell Carcinoma of Urinary Bladder with Intravesical Bacillus Calmette-Guerin (BCG): Our Experience

Aim: To determine efficacy of BCG in T1G3 urinary bladder tumors at department of urology Chandka Medical College Larkana. Patients and Methods: This is retrospective study, patient were selected from hospital record from July 2016 to June 2022. Around 80 included in our study group who were treated in our department for management of high grade non-muscle invasive bladder tumor. After following inclusion and exclusion criteria TURBT were performed and BCG was installed intravesically for induction and maintenance purpose. Patients were followed for 5 years and data was collected on study specific proforma. Results: 80 patients were included in our study with mean age 35year +5.5 SD. Transurethral resection of urinary bladder tumor was performed in all patients with bladder growth. Induction and maintenance instillation of bacillus Calmette-Guerin (BCG) therapy was given to all. The recurrence was noted in 5 patients (6.25%) and the progression was also seen in these 5 patients (6.25%). Disease-specific survival is 93.75% at the follow-up of 5 years. As prevalence of ca bladder is increasing day by day and bladder is sole organ for storing urine so nowadays strategies of treatment is bladder saving surgery. So patient will feel comfortable with natural bladder and on other hand it will minimize complication related to artificially generated urinary bladder. Conclusion: Maintenance BCG therapy for T1G3 bladder tumors is an effective treatment, with satisfactory results and bladder preservation. Keywords: Ca bladder, intravesival chemotherapy, BCG, T1G3 and management.

HMG co-reductase expression and response to intravesical Bacillus Calmette-Guérin in patients with high grade non-muscle invasive urinary bladder cancer receiving statins.

Cardiovascular disease affects over 7 million people in the UK and statins are often prescribed to mitigate cardiovascular risks. The effect of statins on a number of cancers is debated and their effect on Bacillus Calmette-Guérin (BCG) responsiveness in non-muscle invasive urinary bladder cancer (NMIBC) is not fully understood. This study aims to explore the difference in HMG Co-A reductase (HMGCR) expression in NMIBC on immunochemistry in BCG responders and non-responders while on statins. Three hundred and thirty-two cases of intravesical BCG treatment for high-risk NMIBC between November 2003 and December 2017 were identified. Patients taking statins for at least 12 months before the diagnosis of NIMBC and with a follow-up of at least 5 years were included. They were divided into BCG responders and non-responders. Tumour tissue from these patients was immunohistochemically stained and quantitative image analysis carried out to assess and compare HMGCR expression in the groups. This study showed a differential expression of HMGCR in responders vs. non-responders to BCG for high-risk NMIBC on statins. This data should form the basis of a further research and multi-centre study in a larger cohort, using HMGCR as a biomarker of response in patients on statins.

Preoperative Neutrophils to Lymphocytes Ratio in Predicting the Response to BCG in High Grade Non-Muscle Invasive Bladder Cancer

Background Urinary bladder cancer (BC) is a highly prevalent disease affecting more than 400, 000 new cases and 165, 000 deaths yearly, it is the ninth most common cancer in the world, the 13th cause of cancer deaths and the seventh most common cancer worldwide in men with marked male predominance. Aim of the Work To assess the role of preoperative Neutrophils to Lymphocytes Ratio as a predictor for the response to BCG in patients with Non-Muscle invasive Bladder Cancer in patients who underwent Trans-Uretheral Resection of Bladder Tumour (TURBT). Patients and Methods This retrospective cohort study was conducted at tertiary care hospital at Urology department, Ain Shams University hospitals from January 2020 to January 2022 and performed on a total of 46 patients with high grade non-Muscle invasive Bladder Cancer who underwent Trans-Urethral Resection of Bladder Tumor and took BCG course. Results Study results revealed that there was a highly statistically significant relation between preoperative NLR and pathological improvement during Follow up (p-value=0.00) in addition to Tstage and histological grade during Follow up, also there is a statistically significant relation between NLR and tumor size as well as the age of the patient. Conclusion Pre-TURBT NLR when it is high (above 3) is associated with an increased risk of disease recurrence and progression in patients with high grade NMIBC. Moreover, it is an independent predictor of disease recurrence and progression in patients treated with BCG for high grade NMIBC. Pre-TURBT NLR could be a useful blood-based biomarker to improve patients’ risk-stratification facilitating clinical decision-making regarding therapy and follow-up scheduling.

A study to assess the quality of life among patients with high grade non-muscle invasive carcinoma urinary bladder receiving immunotherapy

Background: Urinary bladder lesions are a great health concern as it lies among the top ten most common cancers in the world. These range from benign, harmless lesions that do not recur to life-threatening tumors. The present study was undertaken to assess the quality of life among patients with high-grade non-muscle invasive carcinoma of the urinary bladder receiving immunotherapy. Methods: A hospital-based experimental study was conducted in the Department of General Surgery of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar from April 2021 to July 2022. To examine the Quality of Life of 60 patients before and after immunotherapy, the WHOQOL-BREF tool was employed. The participants were followed for a total of six months, with two follow-ups carried out at intervals of three months each. Results: The pre-test physical scores (20.70±8.66) were substantially lower than the other domains. At three and six months, the psychological scores were 21.93±8.51 and 49.37±12.27 respectively, while social scores were 23.93±12.16 and 49.15±24.09 correspondingly. Environment scores (p=0.45) showed no significant difference between groups after BCG treatment. Conclusions: It was vivid that the negative effects of NMIBC on QOL are most pronounced in the physical realm. Quality of life for those with high-grade NMIBC who had BCG treatment improved significantly across all dimensions except the environment. The quality of life of high-grade NMIBC patients was not affected by any of the socio-demographic characteristics except for education and occupational status.

Underutilization of intravesical chemotherapy and immunotherapy for high grade non-muscle invasive bladder cancer in California between 2006–2018: Effect of race, age and socioeconomic status on treatment disparities

ObjectiveAmong patients diagnosed with non-muscle invasive bladder cancer (NMIBC), those with high risk disease have the greatest risk of recurrence and disease progression. The underutilization of intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been a longstanding concern in clinical practice. This study aimed to determine the disparities present in receipt of adjuvant intravesical chemotherapy and immunotherapy in treatment of patients with high grade NMIBC following initial transurethral resection of a bladder tumor (TURBT). MethodsThe California Cancer Registry data was used to identify 19,237 patients diagnosed with high grade NMIBC who underwent TURBT. Treatment variables include re-TURBT, re-TURBT and intravesical chemotherapy (IVC) and/or BCG. Independent variables include age, sex, race/ethnicity, neighborhood socioeconomic status (nSES), primary insurance payer and marital status at diagnosis. Multiple logistic regression and multinomial regression models were used to examine variation in the treatments received following TURBT. ResultsThe proportion of patients receiving TURBT followed by BCG was similar across all racial and ethnic groups (28%–32%). BCG therapy was higher in patients belonging to the highest nSES quintile (37% for highest vs. 23%–26% for the 2 lowest quintiles). In multiple variable analyses, receipt of any intravesical therapy (IVT) was influenced by nSES, age, marital status, race/ethnicity, and insurance type. Patients in the lowest nSES quintile had a 45% less likelihood of receiving IVT compared to the highest nSES group (OR [95%CI]: 0.55[0.49, 0.61]). Race/ethnicity differences in receipt of any adjuvant therapy were noted in the middle to lowest nSES quintile for Hispanic and Asian/Pacific Islander patients when compared to non-Hispanic White patients. When comparing variation in treatment by insurance type at diagnosis, those with Medicare or other insurance were 24% and 30% less likely to receive BCG after TURBT compared to those with private insurance, (OR [95%CI]: 0.76 [0.70, 0.82] and 0.70[0.62, 0.79]) respectively. ConclusionIn patients with a diagnosis of high risk NMIBC, disparities in utilization of BCG are seen based on SES, age, and insurance type.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.

Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC. Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated. Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort. IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

Clinical results of a phase 1 study of intravesical EG-70 in patients with BCG-unresponsive NMIBC.

512 Background: enGene is developing non-viral gene therapy platforms to deliver nucleic acids (plasmids) to epithelial mucosal tissues such as urothelium of urinary bladder. EG-70 is a nanoparticle formulation of plasmids that activates both innate and adaptive immune responses to activate the immune system within the bladder. The plasmid encodes both IL-12 and activators of the innate immune receptor RIG-I. EG-70 is administered intravesically to elicit local stimulation of anti-tumor immune responses providing durable efficacy in high grade non-muscle invasive bladder cancer (NMIBC) while avoidingsystemic toxicities. Methods: In the Phase 1 study(LEGEND; NCT04752722), escalating doses of EG-70 were administered intravesically to patients with BCG-unresponsive Carcinoma in situ (CIS) NMIBC on weeks 1 and 2 or weeks 1, 2, 5, 6 of 12-week treatment cycle. At the week 12 assessment, patients with stable disease (SD) or complete response (CR), as assessed by urine cytology, cystoscopy, and bladder biopsy, were allowed electively to remain on EG-70 for up to 3 additional 12-week cycles. Results: To date, 19 patients have been treated. There have been no DLTs. AEs (48 GR1, 17 GR 2 and 1 GR3) have been largely consistent with urinary tract instrumentation, and were not dose related. Eighteen patients have completed one cycle of EG-70, and 67% have achieved CR. Fifteen patients with CR or SD at the end of cycle 1 elected to receive additional treatment cycles (continuation rate of 15/18 ( 83%)). Durable CRs were seen at all dose levels. Patients who receive additional cycles are followed for durability of response (Table). Complete Response. Conclusions: These results demonstrate the safety, tolerability and durable therapeutic potential of intravesical EG-70 in patients with BCG-unresponsive CIS. A Phase 2 study will proceed in 2023. Clinical trial information: NCT04752722 . [Table: see text]

Sarcopenia Predicts Disease Progression in Patients with T1 High-grade Non–muscle-invasive Bladder Cancer Treated with Adjuvant Intravesical Bacillus Calmette-Guérin: Implications for Decision-making?

BackgroundSkeletal muscle loss (sarcopenia) has been linked to cancer cachexia and can predict survival in several tumors, including advanced genitourinary malignancies. ObjectiveTo investigate the predictive and prognostic role of sarcopenia in patients with T1 high grade (HG) non-muscle invasive bladder cancer (NMIBC) treated with adjuvant intravesical Bacillus Calmette-Guerin (BCG). Design, setting, and participantsOncological outcomes were evaluated for 185 patients with T1 HG NMIBC treated with BCG at two European referral centers. Sarcopenia, identified from computed tomography scans performed within 2 mo after surgery, was defined as a skeletal muscle index of <39 cm2/m2 for women and <55 cm2/m2 for men. Outcome measurements and statistical analysisThe main endpoint was the association between sarcopenia and disease recurrence and progression. Kaplan-Meier curves and multivariable Cox models were built, and the clinical value of any association was assessed using Harrell’s C index and decision curve analysis (DCA). Results and limitationsSarcopenia was present in 130 patients (70%). On multivariable Cox regression analyses that accounted for the effect of standard clinicopathological prognosticators, sarcopenia was independently associated with disease progression (hazard ratio 3.41; p = 0.02). Addition of sarcopenia to a standard model for prediction of disease progression improved the discrimination of the model from 62% to 70%. DCA revealed superior net benefits for the proposed model in comparison to the strategies of treating all or no patients with radical cystectomy, and in comparison to the existing predictive model. Limitations are inherent to the retrospective design. ConclusionsWe demonstrated the prognostic role of sarcopenia in T1 HG NMIBC. Pending external validation, this tool could be easily incorporated into existing nomograms for prediction of disease progression to improve clinical decision-making and patient counseling. Patient summaryWe looked at the role of loss of skeletal muscle (sarcopenia) as a factor in predicting prognosis for stage T1 high-grade non–muscle-invasive bladder cancer. We found that sarcopenia is a ready-to-use, cost-free marker that could be used to guide treatment and follow-up in this disease, although the results need to be confirmed in other studies.

Predictive clinico-pathological factors to identify BCG, unresponsive patients, after re-resection for T1 high grade non-muscle invasive bladder cancer.

Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis. Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients. A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001). Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes.

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette-Guerin Immunotherapy.

Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette–Guérin (BCG) therapy. Methods: We retrospectively reviewed patient’s medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan–Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92–94), in patients with mGPS 0, 82.2% (CI 95% 78.9–85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4–70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97–99) in patients with mGPS 0, 90% (CI 95% 87–94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion.

Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicenter study.

We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates. Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

Improving practice patterns in patients with newly diagnosed bladder masses treated with transurethral resection

Transurethral resection (TUR) is the mainstay for diagnosis, staging, and treatment of both high-grade and low-grade nonmuscle invasive bladder cancer (NMIBC). It is reported that 51% of initial transurethral resection of bladder tumors (iTURBT) does not contain muscle, which results in higher rates of clinical upstaging on repeat transurethral resection (reTUR) and worse oncologic outcomes. Presence of muscle on iTURBT specimen and performing reTUR within 6weeks in high-risk NMIBC aids in accurate staging and, therefore, guides proper treatment. This study aimed to assess and improve TURBT quality by making surgeons aware of their practice patterns and setting improvement goals. Patients who received TURBT for a newly diagnosed bladder mass were analyzed by retrospective chart review for 9months prior to quality improvement (QI) intervention. Data were collected pertaining to muscle presence/absence on biopsy, pathology of the tumor, risk stratification, whether reTUR was indicated, and time to reTUR. The primary endpoints were the presence of muscle on initial TURBT, whether a reTUR was performed when clinically indicated, and time to reTUR. Tumors requiring reTUR were defined as being HGT1 or HGTa >3cm. The QI intervention, physician education, was then implemented by presenting initial performance results to the physicians, and a second dataset was then collected by prospective analysis for another 9months to assess for changes in practice patterns. A total of 101 patients receiving TURBT were reviewed, including 52 patients prior to and 49 patients following QI intervention. Patients with a history of, or treatment for, bladder cancer were excluded, along withthose without assessment of muscle on pathological analysis. Fisher's exact test was utilized to determine differences in categorical data by comparing each of the following groups prior to and following QI intervention: percent of muscle presence on iTURBT, percent reTUR performed when indicated, and mean time to reTUR in days. A p<0.05 was considered statistically significant. After comparing the TURBT results before and after our QI intervention, we found a significant improvement in the number of patients receiving a reTUR when indicated, with 5/13 (38.5%) before compared to 15/19 (78.9%) after, p=0.03. The number of specimens on iTURBT with muscle present were not significantly different, with 38/52 (73.1%) before and 33/49 (67.3%) after, p=0.66. The average time to reTUR before (32.4days; n=5; range, 21-50days) and after (42.4days; n=15; range, 11-77days) QI intervention was also not significantly different, p=0.28. Our data suggest that critical analysis of physician practice patterns followed by education and setting improvement goals can significantly impact clinical practices and improve quality of care. Future studies will be performed to determine the impact that these changes have on oncologic outcomes.

SC250 - Is it safe to replace retur in T1 high grade non-muscle invasive bladder cancer patients with urine cytology and in-office cystoscopy? Preliminary results from the ongoing prospective multicenter trial “hunire”

SC250 - Is it safe to replace retur in T1 high grade non-muscle invasive bladder cancer patients with urine cytology and in-office cystoscopy? Preliminary results from the ongoing prospective multicenter trial “hunire”

SC11 - Survival outcomes after radical cystectomy versus conservative management for T1 high grade non-muscle invasive micropapillary bladder cancer: a multicentre collaboration by the European Association of Urology – young academic urologists (EAU-YAU): urothelial carcinoma working group

SC11 - Survival outcomes after radical cystectomy versus conservative management for T1 high grade non-muscle invasive micropapillary bladder cancer: a multicentre collaboration by the European Association of Urology – young academic urologists (EAU-YAU): urothelial carcinoma working group

P0750 - Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive micropapillary bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists

P0750 - Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive micropapillary bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists

P0747 - Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive squamous bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists

P0747 - Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive squamous bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists

A phase I trial of chemoimmunotherapy combining bacillus Calmette-Guerin (BCG) and intravesical gemcitabine for patients with BCG-relapsing high-grade nonmuscle-invasive bladder cancer.

TPS509 Background: Intravesical BCG is the most effective treatment for high-grade non-muscle invasive bladder cancer (NMIBC), yet recurrences are common. Patients with BCG-relapsing NMIBC are often re-treated with BCG or BCG with interferon (IFN) with an expected response rate of only 40–60%. Several studies show that a major mechanism of resistance to BCG is high levels of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the pretreatment tumor microenvironment. Gemcitabine is a commonly used intravesical treatment for NMIBC that, in addition to direct anti-tumor cytotoxic effects, may also reduce MDSCs and Tregs. Prior trials combining BCG with intravesical mitomycin C have shown improved efficacy over BCG alone but with higher toxicity. While gemcitabine has been shown to be better tolerated than mitomycin as an intravesical treatment, no study has looked at combined BCG and intravesical gemcitabine. We hypothesize that combining BCG and intravesical gemcitabine will be well tolerated and result in higher response rates by reducing levels of MDSCs and Tregs. A novel aspect of our trial design is the use of a modified continual reassessment method to more accurately identify the maximum tolerated dose instead of the traditional 3 + 3 design used in most NMIBC phase I trials. Methods: This is an investigator-initiated phase I trial (NCT04179162) that will study the safety of alternating intravesical gemcitabine and BCG. Inclusion and exclusion criteria are designed so most patients who would ordinarily be re-treated with BCG or BCG/IFN would be eligible. Patients must have recurrent high-grade NMIBC within 24 months of their last BCG treatment without meeting the criteria for BCG-unresponsive NMIBC. Intravesical gemcitabine is given twice a week on weeks 1, 4, 7, and 10, for a total of 8 doses. BCG (50 mg) is given once a week on weeks 2, 3, 5, 6, 8, and 9, for a total of 6 doses. The trial is monitored using a modified continual reassessment method with increasing dose levels of gemcitabine (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) being evaluated. Adverse events are assessed using the Common Terminology Criteria for Adverse Events version 5.0. The primary objective is to determine the maximum tolerated dose of this combination to inform our planned phase II trial. Correlative studies will look at the immunomodulating effects of gemcitabine by evaluating changes in immune cell populations in serial blood and urine specimens. Tissue and urine will also be evaluated for molecular determinants of response and resistance to the combination. The trial is open to enrollment with 10 of 25 planned patients accrued to date. Clinical trial information: NCT04179162.

Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicentre study

article: Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicentre study - Minerva Urologica e Nefrologica 2021 Jan 13 - Minerva Medica - Journals

Early Experience with Intravesical Gemcitabine-Docetaxel for BCG-Naïve Patients with High Grade Non-Muscle Invasive Bladder Cancer

Intravesical BCG remains a first-line treatment for patients with intermediate/high risk non-muscle invasive bladder cancer (NMIBC) desiring bladder preservation. In the era of BCG shortage, alternative therapies such as sequential dual intravesical gemcitabine and docetaxel (gem/doce) have been described. We report short term outcomes of patients with BCG-Naïve NMIBC treated with gem/doce in lieu of BCG. Patients with high grade NMIBC who had not previously received BCG underwent visually complete TURBT followed by 6 weekly instillations of gemcitabine and docetaxel. At each instillation, patients received 1g of gemcitabine followed by 40mg of docetaxel each for 1-hour dwell. Primary outcome measure was 6-month cystoscopic response rate. Secondary outcome measures include 3-month cystoscopic response rate and progression to MIBC. 18 BCG-naïve subjects received intravesical gem/doce and completed follow up cystoscopy. Initial staging was Ta in 10, T1 in 4, and CIS in 4. At 6-month cystoscopy, 14/18 patients (78%) were visually free of recurrence. Of the 4 patients with CIS at initial staging, 3 (75%) were visually free of recurrence at 6-month cystoscopy and had benign urine cytology. On ensuing TURBT, there were 2 histologic recurrences. One patient had progression from CIS with Ta disease to CIS with T1 disease and one had persistent T1 disease. No patient progressed to muscle invasion during follow up. There were no further instances of tumor recurrence or progression between 3 and 6 months. All patients started on gem/doce (n=18) completed induction without dose reduction or missed instillation due to adverse effects. Sequential adjuvant gemcitabine/docetaxel intravesical therapy after TURBT shows promising 6-month response rates for BCG-naïve high grade NMIBC. Longer follow up is needed to assess durable response or effects on recurrence or progression.

Mini-laparatomy radical cysto-prostatectomy for urinary bladder carcinoma

Introduction: Open radical cysto-prostatectomy (RCP) is the gold standard for invasive urinary bladder cancer in male. Though minimal invasive technique like laparoscopic or robotic assisted surgery is gaining popularity for surgical management in developed countries, open mini laparotomy is equally effective with similar oncological outcome and morbidity result. Our study aims to evaluate the feasibility of Mini-laparotomy RCP with ileal conduit (IC) or neobladder.&#x0D; Methods: This is a descriptive cross-sectional study of 25 patients conducted from October 2016 to December 2019. Nineteen patients had muscle invasive urinary bladder cancer (MIBC), four had multifocal high grade non-muscle invasive bladder cancer (NMIBC) and two were BCG failure patients. Nineteen patients underwent RCP with IC and six with RCP and ileal Neobladder. We analyzed technical difficulty, operative time, blood loss, peri-operative complication for minilaparotomy RCP.&#x0D; Results: The mean age of patients was 63.2 years (46-81years). The mean operative time was 274 minute (180-420 minutes) with mean blood loss of 470 ml (300-2000 ml). Mean post-operative ileus was observed for 2.8 days (2-4 days). All patients stayed in the hospital for mean days of 12.84 (7 to 25 days). All patients were mobilized early with mean intensive care unit (ICU) stay of 2.52 days. Mean lymph node extraction was 17.6. Two patients died of renal failure and hyperosmolar diabetes mellitus.&#x0D; Conclusion: Minilaparatomy RCP is a feasible option in terms of early recovery with acceptable morbidity without compromising the oncological principles.