Invasive Bladder Cancer Research Articles

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

BackgroundA 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.MethodThis 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.ResultsThe 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).ConclusionOur 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.

Preoperative Prediction of Muscle Invasiveness in Bladder Cancer: The Role of 3D Volumetric Radiomics Using Diffusion-Weighted MRI, the VI-RADS Score, or a Combination of Both.

Bladder cancer treatment decisions hinge on detecting muscle invasion. The 2018 "Vesical Imaging Reporting and Data System" (VI-RADS) standardizes multiparametric MRI (mp-MRI) use. Radiomics, an analysis framework, provides more insightful information than conventional methods. To determine how well MIBC (Muscle Invasive Bladder Cancer) and NMIBC (Non-Muscle Invasive Bladder Cancer) can be distinguished using mp-MRI radiomics features. We conducted a study with 73 bladder cancer patients diagnosed pathologically, who underwent preoperative mp-MRI from January 2020 to July 2022. Utilizing 3D Slicer (version 4.8.1) and Pyradiomics, we manually extracted radiomic features from apparent diffusion coefficient (ADC) maps created from diffusion-weighted imaging. The LASSO approach identified optimal features, and we addressed sample imbalance using SMOTE. We developed a classification model using textural features alone or combined with VI-RADS, employing a random forest classifier with 10-fold cross-validation. Diagnostic performance was assessed using the area under the ROC curve analysis. Among 73 patients (63 men, 10 women; median age: 63 years), 41 had muscle-invasive and 32 had superficial bladder cancer. Muscle invasion was observed in 25 of 41 patients with VI-RADS 4 and 5 scores and 12 of 32 patients with VI-RADS 1, 2, and 3 scores (accuracy: 77.5%, sensitivity: 67.7%, specificity: 88.8%). The combined VI-RADS score and radiomics model (AUC = 0.92±0.12) outperformed the single radiomics model using ADC MRI (AUC = 0.83±0.22 with 10-fold cross-validation) in this dataset. Before undergoing surgery, bladder cancer invasion in muscle might potentially be predicted using a radiomics signature based on mp-MRI.

Modulation of ribosomal subunit associations by eIF6 is critical for mitotic exit and cancer progression.

Moderating the pool of active ribosomal subunits is critical for maintaining global translation rates. A factor crucial for modulating the 60S ribosomal subunits is eukaryotic translation initiation factor 6. Release of eIF6 from 60S is essential to permit 60S interactions with 40S. Here, using the N106S mutant of eIF6, we show that disrupting eIF6 interaction with 60S leads to an increase in vacant 80S. It further highlights a dichotomy in the anti-association activity of eIF6 that is distinct from its role in 60S biogenesis and shows that the nucleolar localization of eIF6 is not dependent on uL14-BCCIP interactions. Limiting active ribosomal pools markedly deregulates translation especially in mitosis and leads to chromosome segregation defects, mitotic exit delays and mitotic catastrophe. Ribo-Seq analysis of the eIF6-N106S mutant shows a significant downregulation in the translation efficiencies of mitotic factors and specifically transcripts with long 3'UTRs. eIF6-N106S mutation also limits cancer invasion, and this role is correlated with the overexpression of eIF6 only in high-grade invasive cancers suggesting that deregulation of eIF6 is probably not an early event in cancers. Thus, this study highlights the segregation of eIF6 functions and its role in moderating 80S availability for mitotic translation and cancer progression.

Exploring a Desirable Quadr-mRNAs Panel for Non-invasive and Ultrasensitive Bladder Cancer Diagnosis: In-silico and Clinical Studies.

Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.

Similar genetic profile in early and late stage urothelial tract cancer

IntroductionUrothelial tract cancer (UTC) ranks as the tenth most prevalent cancer and holds the seventh position in terms of mortality worldwide. Despite its prevalence and mortality ranking, there are still gaps in the knowledge of the mutational landscape in patients with advanced disease who have limited therapeutic options after multiple lines of prior treatment. This study compares the genomic and transcriptomic landscape, and targeted treatment options between metastatic UTC (mUTC) patients treated with multiple lines of therapy compared to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC).MethodsWe compared genomic and clinical data from two cohorts: mUTC patients who received multiple lines of therapy and were referred to the Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University of Copenhagen. Data for MIBC UTC patients were acquired from the Cancer Genome Atlas Bladder Cancer (TCGA BLCA) cohort. Biopsies in CoPPO were performed at the time of enrollment. 523 highly important cancer-related genes (TrueSight Oncology-500 targeted sequencing panel) were used from both cohorts for comparative analysis. Analyses included RNA count data to compare predicted molecular subtypes in each cohort separately.ResultsPatients from the CoPPO cohort had a lower median age at first-line treatment than the TCGA BLCA cohort, with no significant gender disparity. The predominant histology was urothelial cell carcinoma in both cohorts. Genomic analysis revealed no significant difference between the top mutated genes in the two cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated a higher frequency of neuroendocrine differentiation in the CoPPO cohort. 13% of patients in the CoPPO cohort received targeted therapy based on genomic findings, and 16% received non-targeted treatment, totaling 29% receiving CoPPO treatment (9 patients). The remaining 71% received best supportive care. Kaplan-Meier analysis showed a non-significant survival benefit for the intervention group in the CoPPO cohort.ConclusionWhen focusing on 523 highly relevant cancer genes, the mutational profile of mUTC patients who have undergone numerous treatment lines resembles that of newly diagnosed MIBC. These alterations can be targeted, indicating the potential advantage of early genomic testing for personalized treatment within clinical trials.

Comparison of thulium and holmium lasers with conventional transurethral bladder resection for non-muscle invasive bladder cancer

Introduction. The gold standard of treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) is transurethral resection of the bladder (TURB) in combination with intravesical therapy. However, this procedure may cause serious complications. At the same time, studies of various lasers for the treatment of NMIBC have demonstrated their safety and efficacy. Despite this, the topic has not yet been fully explored and is not widely practiced in clinical oncology, making further research necessary.Objective. To compare thulium and holmium lasers with conventional TURB for management of non-muscle-invasive bladder cancer (NMIBC).Materials &amp; methods. In our study, depending on the treatment approach, 84 NMIBC-patients were divided into three groups. Group 1 included 27 patients (34.14%), who underwent laser thulium bladder resection; group 2 included 25 patients (29.76%), who underwent laser holmium bladder resection, and group 3 included 32 patients (38.1%), who underwent standard TURB. Prior to surgery, all patients received a standard set of preoperative general clinical and instrumental examinations for bladder cancer, and the choice of surgical approach was based on informed patient consent, taking into account the benefits and risks of the three treatment options. All surgeries were performed in accordance with established protocols.Results. In the TURB group, the surgery time was the longest and totalled in 20.5 ± 7.4 min. Laser technologies reduce the surgery time to 16.3 ± 5.3 min for a holmium laser and to 14.7 ± 5.2 min for a thulium laser. Also, in groups 1 and 2, a shorter duration of postoperative bladder irrigation was noted (4.4 ± 1.8 and 4.7 ± 1.6 hours) and shorter periods of postoperative bladder catheterisation (1.5 ± 0.08 and 1.6 ± 0.08 days) compared to group 3, where these indicators were 16.4 ± 2.5 hours and 2.5 ± 0.13 days, respectively. Among patients undergoing either holmium or thulium surgery, a higher rate of disease-free survival has been noted. Independent prognostic factors that influence the prognosis of NMIBC in all groups include the type of surgery, history of bladder tumors, and pathological stage.Conclusion. The use of laser technology, such as thulium and holmium laser, in bladder wall resection for NMIBC shows promising results and provides a good clinical outcome that is comparable to (and in some cases, superior to) standard TURB.

Comparative analysis of adverse events among intravesical drugs in bladder cancer: a real-world study on FAERS database

ABSTRACT Background Intravesical therapy is a commonly utilized treatment for non-muscle invasive bladder cancer (NMIBC). This study focuses on summarizing the signals of all intravesical drugs and aims to highlight the comprehensive differences in adverse events (AEs) between these drugs. Research design and methods We conducted pharmacovigilance data analysis based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Results We elucidated all signals compared with the overall FAERS database or other administration routes for Bacillus Calmette-Guerin (BCG), mitomycin, gemcitabine, valrubicin, and epirubicin. Notably, the distribution of reported AEs associated with intravesical therapy exhibited a noticeable inclination toward male patients. Furthermore, all five drugs demonstrated a disproportionate distribution in local AEs, particularly in renal and urinary disorders. Additionally, specific signals and findings were summarized for each individual drug. Finally, we highlighted the AEs that resulted in serious outcomes for each drug. Conclusion We have compiled an overview of the AEs tied to intravesical drugs whilst considering their individual distinctions. These insightful findings serve to enrich our comprehension of the safety profiles and potential risks linked to intravesical therapy.

Concomitant decrease of E- and A-FABP expression predicts worse survival in urothelial bladder cancer patients

Non-muscle invasive bladder cancers (NMIBC) pTa-pT1 are depicted by a high risk of recurrence and/or progression with an unpredictable clinical evolution. Our aim was to identify, from the original resection specimen, tumors that will progress to better manage patients. We previously showed that A-FABP (Adipocyte- Fatty Acid Binding Protein) loss predicted NMIBC progression. Here we determined by immunohistochemistry the prognostic value of E-FABP (Epidermal-Fatty Acid Binding Protein) expression in 210 tumors (80 pTa, 75 pT1, 55 pT2-T4). Thus, E-FABP low expression was correlated with a high grade/stage, the presence of metastatic lymph nodes, and visceral metastases (p < 0.001). Unlike A-FABP in NMIBC, E-FABP low expression was not associated with RFS or PFS in Kaplan–Meier analysis. But patients of the overall cohort with a high E-FABP expression had a longer mOS (53.8 months vs. 29.3 months, p = 0.029). The immunohistochemical analysis on the same NMIBC tissue sections revealed that when A-FABP is absent, a high E-FABP expression is detected. E-FABP could compensate A-FABP loss. Interestingly, patients, whose original tumor presents both low E-FABP and negative A-FABP, had the worse survival, those maintaining the expression of both markers had better survival. To conclude, the combined evaluation of A- and E-FABP expression allowed to stratify patients with urothelial carcinoma for optimizing treatment and follow-up.

Gemcitabine versus Bacillus Calmette-Guérin (BCG) in Non Muscle Invasive Transitional Cell Carcinoma of the Bladder after Trans-Urethral Resection

Abstract Background To overcome Bacillus Calmette–Guérin (BCG) shortage and its side effect several studies have compared the safety and efficacy of intravesical gemcitabine with (BCG) for non-muscle invasive bladder cancer. The aim of this work is to evaluate the efficacy of Gemcetabine as a local intravesical treatment of superficial TCC in reducing the risk of recurrence and progression after TURBT in comparison to BCG. Patients and Methods This single blind controlled randomized study Included 82 patients which randomly divided into 2 groups by 1:1 method.Each group included 41 patients, group I will receive gemcitabine. Group II will receive BCG.These patients were diagnosed with superficial bladder tumor (TCC) after TURBT. These patients were followed in the out-patient clinic in the Department of Urology Ain Shams University Hospital and 6th October Health Insurance Hospital during the period from 2017 till 2021. Results After 1 year of follow up 67.6% of group I on the other hand 63.4% of group II were free of tumors. As regard tumor progression, only 2.7% of group I patient had tumor progression while 4.9% of group II had tumor progression but all of these results were statistically not-significant with P. value 0.475. As regard side effects after 1 year of follow up. Regarding dysuria 24 patients 96% in group (I) complained of mild dysuria. On the other hand, 39 patients 95.1 % in group (II) complained of dysuria, 9 of them 21.9 % had sever dysuria and 30 patients 73.2 % had mild dysuria. which was statistically not significant with P. value 0.078. Urine analysis was done after treatment. 33 patients (89.2%) had pus cells in the patients of group I while in group II, all patients had pus cells in urine analysis, which was statistically significant with (P. value 0.046). Conclusion Gemcitabine was associated with nearly similar efficacy and a clinically significant better toxicity profile compared with BCG. Intravesical gemcitabine is a promising drug that may be an option in treating patients with non muscle invasive bladder cancer.

Incidence, initial management and survival of high-risk non-muscle invasive bladder cancer in Northern France

ObjectiveInformation on bladder cancer (BC) according to the risk scoring for recurrence or progression in a general population is scarce despite its clinical relevance. The objective was to describe the characteristics of incident BC in a general population, with a focus on the initial management of high-risk non-muscle invasive BC (HR-NMIBC). MaterialsBC incident in 2011–2012 recorded in a population-based cancer registry were studied. Data was extracted from medical files. NMIBC were classified according to potential risk for recurrence/progression. Individual and tumor characteristics of incident BC were described. Incidence, initial management and survival (12/31/2021) of HR-NMIBC were assessed. ResultsAmong 538 BC cases, 380 were NMIBC [119 low (22.1%), 163 intermediate (30.3%), 98 high (18.2%) risk] and 147 (27.3%) were MIBC. HR-NMIBC diagnostic and therapeutic management [imaging, re-TUR, multidisciplinary team meetings (MDT) assessment, specific treatment] revealed discrepancies with guidelines recommendations. Seventy-two out of 98 cases were assessed in an MDT with a median time from diagnosis of 18days [first quartile: 12-third quartile: 32]. Globally, treatment agreed with MDT decisions. Intravesical instillation was the most common treatment (n=56) but 27 HR-NMIBC did not receive specific treatment after TUR. Five and 10years overall survival was 52% [42–63] and 41% [31–51], respectively. Five years net survival was 63% [47–75]. ConclusionsDespite National cancer plans aiming to improve care giving and despite the severity of HR-NMIBC, guideline-recommended patterns of care were underused in this region. This may deserve attention to identify obstacles to guideline adoption to try to improve BC patient care and survival. Level of evidence3

Enhanced Recovery after Surgery Protocol (ERAS) versus Standard Protocol for Undergoing Radical Cystectomy in an Egyptian Population

Abstract Background bladder cancer has been one of the commonest cancer. The gold standard for treatment of muscle invasive bladder cancer is radical cystectomy with pelvic lymphadenectomy and associated with considerable morbidity and mortality and healthcare cost. Enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care pathways designed to achieve early recovery after surgical procedures. Aim and Objectives The aim of this study was to compare between the standard preoperative bowel preparation (SP) and ERAS protocol in terms of postoperative length of stay (LOS) and postoperative morbidity. Subjects and Methods This was a prospective randomized study was conducted in Ain shams university hospital – Alexandria university hospital involving fifty (50) patients were randomly divided into two equal groups twenty-Five (25) patient in group A follow ERAS protocol and twenty-Five (25) patients in group B following standard protocol. The duration of the study ranged from 6-12 months. Results There was statistically significant difference found between group A and group B regarding the studied parameters ( Readmission in 30 days, Ileus, Vomiting, and UTI) while there was no statistically significant difference between them regarding (early mobilization, urine leakage, dehesince and DVT), there was no statistically significant difference found between group A and group B regarding (Length of stay). Conclusion In patients undergoing radical cystectomy, enhanced recovery protocol is considered as a safe procedure and not associated with any increase in intraoperative and postoperative complications compared to standard protocol. The length of hospital stay was shorter in ERAS group.

Investigation of risk factors for vaginal dehiscence and development of small bowel evisceration after robot-assisted radical cystectomy for female bladder cancer and an improved vaginal reconstruction technique to prevent its onset.

Transvaginal organ prolapse, such as small bowel evisceration, is a rare complication after radical cystectomy (RC) in female patients with invasive bladder cancer, However, it often requires emergency surgical repair. Here, we describe our experience with such a case and a review of similar previously reported cases, along with evaluation of the risk factors. We also propose a vaginal reconstruction technique to prevent this complication during robot-assisted laparoscopic radical cystectomy (RARC). A total of 178 patients who underwent laparoscopic radical cystectomy (LRC) or RARC were enrolled, 34 of whom (19%) were female. One of the 34 female patients had transvaginal small bowel evisceration after RARC. We evaluated our case and six such previously reported cases, to determine vaginal reconstruction techniques during RARC to prevent this complication postoperatively. Median age of these cases was 73 (51-80) years, and all patients were postmenopausal. The median time to small bowel evisceration was 14 (6-120) weeks postoperatively. In addition, we changed the methods of the vaginal reconstruction technique during RARC from the conventional side-to-side closure technique to the improved caudal-to-cephalad closure technique. Since implementing this change, we have not experienced any cases of vaginal vault dehiscence or organ prolapse. Transvaginal small bowel evisceration after RC can easily become severe. Therefore, all possible preventive measures should be taken during RARC. We believe that our vaginal reconstruction techniques might reduce the risk of developing this complication.

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

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

No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

Establishing an Intravesical Doublet Chemotherapy Clinic for Nonmuscle-Invasive Bladder Cancer Patients.

Intravesical sequential doublet chemotherapy (SDC) is being used increasingly as a rescue treatment for nonmuscle-invasive bladder cancer failing bacillus Calmette-Guérin (BCG), as single-agent chemotherapies are less effective, especially for carcinoma in situ. Considering the current BCG shortage, intravesical SDC also provides an efficacious alternative to BCG. Our aim is to detail the implementation to assist with establishing an efficient and practical intravesical SDC clinic for urologic practice. We searched PubMed for published studies with the Medical Subject Heading of "intravesical chemotherapy" and "non-muscle invasive bladder cancer." The search was limited to English-language journals and full papers only. The initial search resulted in 260 articles, of which 20 relevant studies were selected. Five important processes were identified in the successful and efficient administration of intravesical SDC: (1) patient preparation, (2) medication procurement, (3) medication administration, (4) medication immediate aftermath, and (5) patient instruction and education. Safety precautions should be taken when handling each chemotherapy drug. A clinical pharmacist may be required for drug preparation. An important step in providing intravesical SDC is to use a closed system for the instillation of the chemo-solution. A special protocol should be adopted for every drug with its proper dwell time. The induction course consists of weekly instillation for 6 weeks. If an initial response is noted, maintenance therapy is recommended, typically monthly for 24 months. Successful intravesical SDC clinics necessitate appropriate patient selection, standardized workflow procedures, patient education, and good communication between the urologist, clinical pharmacists, and oncology nurses.

Authors reply Re: Sharma AP, Singh PP, Chauhan R, Panda I, Devana SK, Bora GS, et al. Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting. Indian J Urol 2024;40:127-32.

Authors reply Re: Sharma AP, Singh PP, Chauhan R, Panda I, Devana SK, Bora GS, et al. Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting. Indian J Urol 2024;40:127-32.

Editorial Comment on “Sequential Intravesical Chemotherapy for Treatment Naïve, High-Risk Non-Muscle Invasive Bladder Cancer: Oncologic Outcomes, Tolerance, and Comparison to Contemporary Controls”

Editorial Comment on “Sequential Intravesical Chemotherapy for Treatment Naïve, High-Risk Non-Muscle Invasive Bladder Cancer: Oncologic Outcomes, Tolerance, and Comparison to Contemporary Controls”

Re: Sharma AP, Singh PP, Chauhan R, Panda I, Devana SK, Bora GS, et al. Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting. Indian J Urol 2024;40:127-32.

Re: Sharma AP, Singh PP, Chauhan R, Panda I, Devana SK, Bora GS, et al. Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting. Indian J Urol 2024;40:127-32.

Low-grade Urothelial Carcinoma Recurs at a Tempo that Naturally Accelerates Over Time

ObjectivesTo investigate the cadence of recurrence in patients with low grade intermediate-risk non-muscle invasive bladder cancer (LG IR-NMIBC) based on clinical determinants. We aim to describe patterns in rates of recurrence to better inform surveillance regimens for this chronic, burdensome, and costly disease. MethodsUsing baseline and follow-up data from participants in the West Midlands’ (United Kingdom, UK) Bladder Cancer Prognosis Programme (BCPP), we assessed overall recurrence rate and recurrence-free intervals throughout the follow-up period for IR-NMIBC participants. Recurrence-free intervals were calculated using the Kaplan-Meier method. ResultsWe identified 379 patients with G1/G2 pTa tumors classified as intermediate risk. Median age was 70 and 284/379 (75%) were male. The median follow-up time was 4.2 years (95% CI: 3.9-4.8). After 5 years of follow-up, 53% of patients had at least one recurrence. One-year recurrence-free survival (RFS) was 75% and 4-year RFS was 50%. The median time to or between 1st, 2nd, 3rd, 4th, and 5th sequential recurrences was 49, 19, 12, 14, and 10 months, respectively. ConclusionsOver half of patients with IR-NMIBC are destined to recur. Our data suggest that a subset of patients experience acceleration of recurrence over time and that this acceleration may serve as a potential kinetic biomarker for these individuals that could inform surveillance intervals and future treatment strategies.

Bladder Tumor-Focused Adaptive Radiation Therapy: Clinical Outcomes of a Phase I Dose Escalation Study

Purpose/ObjectivesWe determine the maximum tolerated tumour focused dose (MTD) for the radical treatment of muscle invasive bladder cancer (MIBC) enabled by image guided adaptive radiotherapy (IGART) and long-term clinical outcomes. Materials/Methods: Fifty-nine patients with T2-T4aN0M0 unifocal urothelial MIBC suitable for daily radical radiotherapy were recruited prospectively to an ethics approved protocol (XX). The uninvolved bladder (PTVbladder) was planned to 52Gy in 32 fractions (f). The bladder tumour (PTVtumour) was planned to an assigned dose level of 68, 70, 72, or 74Gy. If organ at risk (OAR) dose constraints were violated, then PTVtumour was planned to 64Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using CTCAE v3.0; late toxicity was evaluated using RTOG criteria. The MTD was predefined as the highest dose level with estimated probability of ≤ 15% ≥G3 late toxicity and observed rate <50% acute G3 and <10% acute G4 toxicity. ResultsTwenty-six patients were assigned to 68Gy, of whom 6 were planned to 64Gy; 29 patients were assigned to 70Gy of whom 1 was planned to 68Gy, 2 patients were assigned and planned to 72Gy; no patients were assigned to 74Gy. Three patients did not complete treatment as planned, of whom only 1 patient stopped treatment because dose limiting toxicity occurred. The MTD was 70Gy. Acute genitourinary (GU) and gastrointestinal (GI) G3 acute toxicity was seen in 19% and 7% patients respectively. No grade 4 GU or GI toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% patients respectively. The 5-year overall survival was 58% (95% CI 44-71%). The bladder preservation rate was 89% (95% CI, 88 to 96%) with 6 patients not retaining native bladder function. ConclusionBladder tumour focused dose escalation to 70Gy using IGART is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomised control trial (XXXXX).