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We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation., (© 2024. The Author(s).)

Introduction: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC)., Methods: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared., Results: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively)., Conclusion: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment., (© 2023 S. Karger AG, Basel.)

Purpose: Detecting bladder cancer (BC) in routine CT images is important but is sometimes difficult when cancer is small. We evaluated the ability of 40-keV advanced monoenergetic images to depict BC., Materials and Methods: Fifty-two patients with a median age of 74 years (range 45-92) who were diagnosed as BC with transurethral resection or cystectomy, were included. They were examined with contrast-enhanced dual-energy CT (DE-CT) and advanced virtual monoenergetic images (40 keV) were reconstructed. For evaluating depictability of BC on 40-keV or virtual-120-kVp images, the difference in CT number between the cancer and bladder wall (BC-BW value) were calculated. We also subjectively assessed depictability of BC in virtual-120-kVp and 40-keV images using a 4-grade Likert scale (3: clear, 0: not visualized)., Results: In 42 of 52 patients, BC-BW values could be calculated because BC was detected on CT images. The mean BC-BW value at 40 keV was significantly higher than that of virtual 120 kVp [80.5 ± 54 (SD) vs. 11.4 ± 12.5 HU, P < 0.01]. Average scores of subjective evaluations in the virtual-120-kVp and 40-keV images were 1.7 ± 1.2 and 2.1 ± 1.2, respectively (P < 0.001)., Conclusion: The advanced monoenergetic reconstruction technique reconstructed using DE-CT image is useful to depict BC., (© 2021. The Author(s).)

Introduction: This study had two objectives: (i) to evaluate oncological outcomes in a long-term follow-up of patients with bladder cancer after reduced-port laparoscopic radical cystectomy (RP-LRC) and (ii) to assess the effect of modified Glasgow prognostic scores (mGPS) on patient outcomes., Methods: Consecutive patients (n = 100) who received RP-LRC between March 2012 and December 2018 at our institution and affiliated hospital were retrospectively reviewed. Preoperative serum albumin and C-reactive protein levels were determined. Patients were grouped based on clinical T stage (≤cT2: n = 75, ≥cT3: n = 25) using pooled cumulative data. Oncological outcomes and mGPS as a prognostic biomarker were analyzed retrospectively. Kaplan-Meier curves displayed recurrence and survival rates. Univariate and multivariate Cox regression analyses evaluated potential prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS)., Results: Patient characteristics between the two groups were statistically similar for preoperative hematological and mGPS status, blood loss level, rate of allogeneic transfusion, and pneumoperitoneum time. After a median follow-up period of 55 months, 40/100 patients experienced disease relapse. RFS and CSS for ≤cT2 were significantly less than for ≥cT3 (p < 0.001, p < 0.05, respectively). Distant metastasis occurred in 30 patients with similar distributions of relapse sites between T-stage cohorts. Median RFS for mGPS 1/2 were 18.9 (95% confidence interval [CI]: 8.8-not assessed [NA]) and 35.0 (95% CI: 8.7-NA) months, respectively, significantly worse than for mGPS 0 (median NA, 95% CI: NA-NA); CSS was similar. Univariate and multivariate analyses revealed ≥cT3 stage, worse clinical N stage, and poor mGPS status were significant prognostic factors for short RFS and CSS., Conclusions: A large proportion of bladder cancer patients who undergo RP-LRC experience relapse, with ≥cT3 stage, worse clinical N stage or poor mGPS status identified as significant prognostic factors. Our findings may contribute to improved surgical procedures for such patients., (© 2022 S. Karger AG, Basel.)

Background: After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients., Methods: A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS)., Results: Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6-17.6] than A (7.6 months, 5.3-8.8). By sub-group analysis, patients received no additional treatment (Naïve, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naïve and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3-8.8; Group A, 7.6 months, 4.7-13.8; Naïve, 25.7 months, 14.0-31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD-salvage PEM and PEM-salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12-3.45, hazard ratio (HR): 1.97; 95% CI 0.24-0.71, 0.41, respectively]., Conclusion: Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome., (© 2021. Japan Society of Clinical Oncology.)

Background/aim: Predicting the prognosis of metastatic urothelial carcinoma (mUC) patients is needed for clinical decisions. We examined the value of a modified Glasgow prognostic score (mGPS) as a predictive marker for mUC patients., Patients and Methods: In a multicenter study, 68 mUC patients received short hydration gemcitabine/cisplatin (shGC) and 74 received pembrolizumab (PEM). Patients were allocated according to mGPS. Progression-free (PFS) and cancer-specific (CSS) survival were examined., Results: Higher mGPS reflected poorer PFS and CSS in shGC (p=0.03, p<0.0001, respectively) and PEM (p=0.02, p<0.001, respectively) patients. PFS for the high mGPS group was longer than that of the low mGPS group in the two cohorts (p <0.0001 for both), with similar CSS results (p<0.0001 and p<0.001, respectively). Multivariate analyses revealed high mGPS was a risk factor for poor CSS in both cohorts (HR=3.55, p<0.001, and HR=2.21, p<0.01, respectively)., Conclusion: In the mUC patients receiving shGC or PEM, mGPS was a predictive prognostic marker., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: In March 2019, cefazolin availability was limited owing to the contamination of the drug substance. In addition, there was a difficulty in supplying drugs alternative to cefazolin, such as cefotiam and cefmetazole. In our Department of Nephro-urology, we used fosfomycin-based drugs to substitute cefazolin as perioperative preventive antibacterial drugs. In this study, we aimed to evaluate the usage status of perioperative prophylactic antibacterial drugs before and after the period of limited cefazolin supply and to investigate the efficacy and safety of fosfomycin sodium in preventing infections following transurethral resection of bladder tumor., Methods: We enrolled 346 patients who underwent transurethral resection of bladder tumor in our department from April 2018 to August 2020. The patients received the following perioperative antibacterial agents: cefotiam (n = 146), fosfomycin (n = 166), and other antibacterial agents (n = 34). There was no significant difference in the median age or surgery time., Results: The median length of hospital stay was 6, 5, and 5 days in the cefotiam, fosfomycin, and other antibacterial groups, respectively, with significant difference. The median maximum postoperative temperature was 37.1 °C in all groups, with no significant difference. There were no differences in C-reactive protein, aspartate aminotransferase, and alanine aminotransferase levels determined by postoperative blood tests; preoperative and postoperative urinary white blood cell counts; preoperative urine bacterial counts; and surgery-related infection requiring additional antibiotic treatments among the groups., Conclusions: The use of fosfomycin-based agents helped overcome the limited supply of cefazolin without worsening clinical outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of the study was to examine the effectiveness of a modified-short hydration gemcitabine and cisplatin (m-shGC) regimen for patients with metastatic urothelial carcinoma (mUC) and to assess the efficacy of a geriatric nutritional risk index (GNRI) with regard to prognosis., Patients and Methods: From January 2016 to July 2020, 68 patients with mUC underwent first-line m-shGC therapy with 70 mg/m2 cisplatin and 1,000 mg/m2 gemcitabine (days 1, 8, and 15), with 2,050 mL fluid replaced on the first day of each 28-day cycle. Prior to the start of treatment, the serum neutrophil-to-lymphocyte ratio (NLR), and levels of albumin and C-reactive protein (CRP) in serum, as well as body heights and weights were measured. Patients were grouped according to GNRI <92 (low) or ≥92 (high). The analysis of data was done retrospectively., Results: Median follow-up was found to be 12.9 (range 1.7-50.2) months and the objective response rate (ORR) was 54.4% after m-shGC treatment. The ORR was significantly different when high and low-GNRI groups were compared (ORR: 28.0 vs. 69.8% in low- vs. high-GNRI groups). Median overall survival (OS) was calculated as 8.6 (95% confidence interval [CI]: 5.4-21.3) and 34.5 (95% CI: 20.5-NA) months for low- and high-GNRI groups, respectively (p < 0.0001). Unlike for NLR and CRP, univariate and multivariate analyses revealed that low GNRI and visceral metastases were significant prognostic factors for short OS., Conclusions: First-line m-shGC showed a survival benefit for mUC, with GNRI a useful prognostic biomarker., (© 2021 S. Karger AG, Basel.)

Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine enhanced rat urinary bladder carcinogenesis in a two-stage carcinogenesis model. Nicotine also induced cytotoxicity in the bladder urothelium in a short-term study. In the present study, male rats were treated with nicotine (40 ppm) in drinking water co-administered with the NADPH oxidase inhibitor, apocynin (0, 250 or 750 mg/kg) in diet for 4 weeks. The apocynin treatment induced no clinical toxic effects. Reduction of reactive oxygen species (ROS) by apocynin was confirmed by immunohistochemistry of 8-OHdG in the bladder urothelium. Incidences of simple hyperplasia, cell proliferation and apoptosis were reduced by apocynin treatment in the bladder urothelium. However, despite reduction of cell proliferation (labeling index), apocynin did not affect the incidence of simple hyperplasia, apoptosis, or ROS generation in the kidney pelvis urothelium, in addition to 8-OHdG positivity induced by nicotine being lower. In vitro, apocynin (500 μM) reduced ROS generation, but induced cell proliferation in bladder cancer cell lines (T24 and UMUC3 cells). These data suggest that oxidative stress may play a role in the cell proliferation of the bladder urothelium induced by nicotine., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The purpose of this study was to assess the efficacy of Bacillus Calmette-Guerin (BCG) therapy after a second transurethral resection (TUR) in new onset high-grade T1 bladder cancer., Methods: From January 2008 to September 2013, 207 patients with new onset high-grade T1 bladder cancer after an initial TUR were treated at our university and at affiliated hospitals. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors for intravesical recurrence were analyzed., Results: Among a total of 207 patients, 42 patients were treated with BCG therapy following a second TUR (group 1), 23 were treated with second TUR alone (group 2), 72 were treated with BCG alone (group 3), and 70 were treated without a second TUR or BCG. The median patients' age was 72.0 years, and the median follow-up period was 33.5 months. The second TUR revealed that 34 patients (52 %) had residual cancer. Between groups 1 and 2 and groups 1 and 3, the differences in RFS were statistically significant (p = 0.002 and 0.045, respectively). In addition, BCG therapy was the most significant factor to predict RFS after the second TUR. Among the 31 patients whose pathology of the second TUR was pT0, only 1 of 12 patients (8 %) in group 1 and 11 of 19 patients (58 %) in group 2 had a recurrence., Conclusions: BCG instillation following a second TUR decreases intravesical recurrence, even if the pathology of the second TUR is pT0.

Objective: The objective of this study was to characterize MRI findings of inverted urothelial papilloma of the bladder., Materials and Methods: Data pertaining to 16 patients with 18 pathologically proven inverted urothelial papillomas of the bladder who had undergone MRI were retrospectively collected from seven institutions. The shape and surface characteristics of the tumors were evaluated using T2-weighted MR images. In addition, the signal intensity of inverted urothelial papillomas was visually assessed on T1-weighted, T2-weighted, and DW images and on early and delayed phase contrast-enhanced images., Results: The shape of the 18 inverted urothelial papillomas of the bladder was classified as polypoid with a stalk for 16 tumors (89%) and polypoid without a stalk for two tumors (11%). All stalks were surrounded by urine in the bladder. A total of 15 of the tumor surfaces (83%) were nonpapillary and three (17%) were papillary. All 12 of the inverted urothelial papillomas for which evaluable T1-weighted images were available were isointense with the bladder wall. The lesions had a slightly higher signal intensity than the bladder wall in 15 of the patients (83%) and showed isointensity with the bladder wall in three patients (17%). A total of three patients (17%) had tiny hyperintense foci noted on T2-weighted images. All 16 of the inverted urothelial papillomas examined by DWI had very high signal intensity. All 13 of the lesions for which early phase images were obtained using dynamic contrast-enhanced MRI showed strong enhancement. When compared with early phase images, delayed phase images of the same 13 lesions showed that enhancement was stronger in two lesions (15%), similar in six lesions (46%), and weaker in five lesions (38%)., Conclusion: On MRI, the typical appearance of inverted urothelial papillomas of the bladder is a polypoid shape with a nonpapillary surface and a thin short stalk surrounded by urine. Cystic foci are also occasionally seen within the tumor.

Background: To explore the safety, efficacy, and oncological outcome of 3-port laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC) in patients older than 75 years., Materials and Methods: From June 2010 to July 2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC group=8; ORC group=8). Demographic parameters, operative variables, and perioperative outcome in the 2 groups were retrospectively collected, analyzed, and compared., Results: Patients in both groups had comparable preoperative characteristics. A significantly longer operating time (476 vs. 303 min, P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed in the LRC group compared to the ORC group. Infection and ileus were the most common early complications after surgery. Patients who underwent ORC suffered from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs. 12.5%, P=0.521) than the LRC group, but the difference was not significant., Conclusions: Judging from this initial trial, 3-port LRC can be safely carried out in elderly patients. We suggest 3-port LRC as the primary intervention to treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly patients with an otherwise relatively long life expectancy.

Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion-weighted imaging (DWI) of urinary bladder cancer for T-staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T-stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2-weighted imaging or enhanced MRI and could lead to over-staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy., (Copyright © 2013 Wiley Periodicals, Inc.)

Aim: To evaluate magnetic resonance imaging (MRI) findings of granulomatous prostatitis (GP) developing after intravesical Bacillus Calmette-Guérin (BCG) therapy., Materials and Methods: Ten patients with pathologically proven GP underwent prostatic MRI. Lesion shape and signal intensity (SI) were evaluated on T2-weighted (T2WI), T1WI, and diffusion-weighted imaging (DWI)., Results: Polygonal nodular lesions with notches, diffuse lesions, and cystic lesions with mural nodules were seen in two, six, and one patients, respectively. The remaining patient had a diffuse and cystic lesion. All diffuse lesions showed higher SI than muscle on T1WI and higher SI than the normal peripheral zone (PZ) on DWI. On T2WI, six of seven diffuse lesions showed a slightly lower SI than bone marrow and the remaining one lesion was iso-intense. All nodular lesions showed a low SI similar to muscle on T2WI and were iso-intense to muscle on T1WI. On DWI, two each of the four nodular lesions showed slightly lower SI and slightly higher SI than the normal PZ, respectively. All contents within the cyst and mural nodules showed markedly high and low SI on T2WI, respectively. On DWI, all fluids within cysts showed markedly high SI. One each of the mural nodules showed slightly higher SI and slightly lower SI than the normal PZ on DWI., Conclusion: Three main MRI patterns of GP were identified: diffuse, nodular, and cystic with mural nodule; among them, the diffuse type was the most common. Cystic lesions with mural nodules could accompany the lesion., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: A series of bacillus Calmette-Guérin (BCG) bladder instillations is the gold standard therapy to prevent recurrence after transurethral resection of bladder tumor (TUR-Bt) of non-muscle-invasive bladder cancer (NMIBC). However, in some cases the outcome is not optimal with the standard 6- to 8-week protocol and therefore interest has focused on additional maintenance therapy. The present study was conducted to assess the utility of single monthly intravesical instillation treatments for up to 1 year in Japanese patients., Methods: A total of 75 stage Ta and T1 patients who had undergone TUR-Bt were retrospectively evaluated, all first receiving 80 mg BCG (Tokyo 172 strain) given once a week, 6-8 times, for primary prophylaxis. Comparison was then made of groups with (group A, 48 patients) and without (group B, 27 patients) additional maintenance BCG therapy given once a month 6-8 times., Results: Recurrence-free survival rates at 5 years in groups A and B were 83.0 and 51.9% (P = 0.006), despite the greater proportion of T1 patients and the longer follow-up period in the group A patients. Significant protection against recurrence persisted on multivariate analysis with adjustment for age, stage, grade, and tumor number., Conclusions: These findings indicate maintenance BCG therapy of single intravesical instillations given once a month with our protocol to be definitely effective for prophylactic use, especially in stage Ta patients. Further evaluation of parameters such as the continuance period and dose protocol is warranted.

Objective: The guidelines on indications for prophylactic use of Bacille Calmette-Guerin (BCG) against non- muscle-invasive bladder cancer (NMIBC) have changed over the years. In order to assess the impact on outcome, the present retrospective comparison of BCG efficacy by time period with Japanese patients was conducted., Patients and Methods: A total of 146 cases of NMIBC treated with BCG since February 1985 were retrospectively evaluated. All patients received 80 mg of BCG (Tokyo 172 strain) six to eight times a week for prophylactic use. Comparison was made among three historical groups (Group A: 1980's, 39 cases; Group B: 1990's, 61 cases; Group C: 2000's, 46 cases)., Results: In total, recurrence was seen in 55 of the 146 cases (37.7%), and progression in 14 (9.6%), 1 patient dying of cancer. These overall results were similar to those outlined in previous reports. However, the outcomes of this time-period-based analysis indicated a tendency for a shorter time to recurrence in patients after 2000, although a log-rank test showed no significance (P=0.229). Seven of the cases featuring progression (i.e., half of all such cases) were among the 46 Group C patients (15.2%). Excluding these progressive cases, there was no significant difference among the remaining 132 patients in the three groups., Conclusion: This study results revealed a tendency for a lower non-recurrence rate after 2000 in our series. This could stem from a number of factors, including changes in BCG indication criteria and the evolution of histopathological diagnostic criteria.