Bacillus Calmette-Guerin Group Research Articles

Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette–Guérin for the treatment of upper tract carcinoma in situ

IntroductionNephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette–Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS. MethodsA single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology. ResultsThe final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59–9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group. ConclusionEndoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted.

PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette-Guérin (BCG) Therapy.

In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette-Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the 'combined positivity score' (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan-Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, p = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (p = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited.

Prostate Biopsy May Not Be Indicated Early after Bacillus Calmette Guérin Treatment.

Bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer frequently causes an intraprostatic BCG granuloma. We investigated the optimal timing for a prostate biopsy after BCG treatment by retrospectively analyzing the cases of 22 patients with non-muscle-invasive bladder cancer who underwent a prostate biopsy after BCG treatment at our institute (2013-2017). Biopsies were indicated for a rising prostate-specific antigen (PSA) level, positive digital rectal examination findings, or the appearance of de novo low apparent diffusion coefficient lesions on MRI. The control group was comprised of 28 age- and PSA-matched patients. The relationships among the cancer detection rate and the patients' PSA levels and MRI findings were analyzed. Prostate cancer was detected by biopsy in only 13.9% (3/22) of the patients in the BCG group but in 78.5% (22/28) of the control patients (p=0.0001). The three patients in the BCG group in whom prostate cancer was detected had all undergone the biopsy > 1 year after their BCG treatment. The remaining biopsies were performed within 1 year after BCG treatment and resulted in no diagnoses of prostate cancer. We suggest that performing a prostate biopsy early after BCG treatment is not informative or useful.

Comparative analysis of recurrence rates between intravesical gemcitabine and bacillus Calmette-Guérin induction therapy following transurethral resection of bladder tumors in patients with intermediate- and high-risk bladder cancer: A retrospective multicenter study.

This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette-Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis.

To compare adjuvant hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C and standard Bacillus Calmette-Guerin (BCG) therapy in terms of oncological outcomes and adverse events in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). The data of patients with high-risk papillary NMIBC treated with adjuvant intravesical BCG instillations or HIVEC in our institution between June 2017 and August 2022 were analyzed retrospectively. Twenty-four patients who received HIVEC were matched 1:1 with patients receiving BCG therapy based on tumor characteristics (tumor stage and grade), age, gender, smoking status, and the number of tumors (single or multiple). HIVEC and standard BCG treatments were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and adverse events. Forty-eight patients (24 in the BCG group and 24 in the HIVEC group) were included in the study. The median follow-up times of the BCG and HIVEC groups were 32 [interquartile range (IQR): 28.0-47.8] and 28 (IQR: 16.7-41.8) months, respectively (p = 0.11). There was no significant difference between the groups in terms of the 24-month RFS (BCG 83% vs HIVEC 88%, p = 0.64) and the 24-month PFS (BCG 100% vs HIVEC 94%, p = 0.61). Regarding the safety profile, at least one adverse event occurred in 13 (54%) of the patients in the BCG group and 12 (50.0%) of those in the HIVEC group (p = 0.77). This study demonstrated that HIVEC with mitomycin C has a similar oncological efficacy and safety profile to standard BCG therapy in high-risk NMIBC.

Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial.

The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes. There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24). In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes. NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).

Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis.

To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.

Subcutaneous Bacillus Calmette-Guérin Administration Induces Innate Training in Monocytes in Preweaned Holstein Calves.

The bacillus Calmette-Guérin (BCG) vaccine, administered to prevent tuberculosis, is a well-studied inducer of trained immunity in human and mouse monocytes. We have previously demonstrated that aerosol BCG administration induces innate training in calves. The current study aimed to determine whether s.c. BCG administration could induce innate training, identify the cell type involved, and determine whether innate training promoted resistance to bovine respiratory syncytial virus (BRSV) infection, a major cause of bovine respiratory disease in preweaned calves. A total of 24 calves were enrolled at 1-3 d of age and blocked by age into two treatment groups (BCG, n = 12; control, n = 12). BCG was given s.c. to preweaned calves. The control calves received PBS. We observed a trained phenotype, demonstrated by enhanced cytokine production in response to invitro stimulation with LPS (TLR-4 agonist) in PBMCs and CD14+ monocytes from the BCG group 2 wk (IL-1β, p = 0.002) and 4 wk (IL-1β, p = 0.005; IL-6, p = 0.013) after BCG administration, respectively. Calves were experimentally infected via aerosol inoculation with BRSV strain 375 at 5 wk after BCG administration and necropsied on day 8 postinfection. There were no differences in disease manifestation between the treatment groups. Restimulation of bronchoalveolar lavage fluid cells isolated on day 8 after BRSV infection revealed enhanced IL-1β (p = 0.014) and IL-6 (p = 0.010) production by the BCG group compared with controls. In conclusion, results from our study show that s.c. administration of the BCG vaccine can induce trained immunity in bovine monocytes and influence cytokine production in the lung environment after BRSV infection.

761 Effectiveness of Chemohypothermia with Mitomycin C vs Immunotherapy with BCG in High Risk Non Muscle Invasive Bladder Cancer Patients

Abstract Aim Initial data to compare the effectiveness of Chemohypothermia with Mitomycin C (MMC) and Immunotherapy with Bacillus-Calmette-Guerin (BCG) in High risk Non muscle invasive bladder cancer (NMIBC). Method Sixty six patients who underwent Trans-urethral resection of bladder tumor (TURBT) were divided into two equal groups; hyperthermic intravesical chemotherapy group and BCG group. Six intravesical instillation's (one per week) of 40mg of hyperthermic MMC diluted in 40ml of distill water and heated at 43 C were given to patients for 60 min with HIVEC machine. For BCG group intravesical doses of BCG, once weekly for 6 weeks were administered at concentration of 80mg diluted in 50ml of normal saline. Follow up check cystoscopy at 3 months from initial TURBT was done to check effectiveness of both treatments. Patients were also accessed for side effects during the treatment. Results 28 patients (84.8%) had no recurrence and 5 patients (15.2%) had recurrence in chemohypethermia group while in BCG group 29(87.8%) patients had no recurrence and 4(12.2%) patients had recurrence. 3(9%) patients had bladder spasms, 1(3%) had hematuria, 3(9.1%) had Urinary tract infection (UTI) while 26(78.8%) had no adverse effect in Chemohyperthermia group. In BCG group, 1(3%) had bladder spasm, 4(12.4%) had hematuria, 5(15.2%) had UTI and 23(69.5%) had no adverse effect. Conclusions Chemohyperthermia is safe and efficacious treatment choice in patient suffering from NMIBC with outcomes comparable with BCG treatment and improved side effect profile.

Oncological Outcomes for Patients with European Association of Urology Very High-risk Non–muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin or Early Radical Cystectomy

BackgroundEuropean Urology Association (EAU) guidelines recommend immediate radical cystectomy (early RC) for patients with very high-risk (VHR) non–muscle invasive bladder cancer (NMIBC), with bacillus Calmette-Guérin (BCG) recommended only for those who refuse or are unfit for RC. ObjectiveTo describe oncological outcomes following BCG or early RC in a contemporary cohort of patients with VHR NMIBC (EAU criteria). Design, setting, and participantsPatients diagnosed with VHR NMIBC between 2000 and 2020 were identified from our institutional NMIBC registry. Outcome measurements and statistical analysisThe primary outcomes were overall survival (OS) and cancer-specific mortality (CSM). Secondary outcomes were the progression rate and high-grade recurrence (HGR) rate for patients receiving BCG. Results and limitationsWe identified 235 patients with VHR NMIBC, of whom 157 (67%) received BCG and 78 (33%) underwent early RC. The median follow-up was 52.8 mo. OS and CSM rates were 80.2% and 5.3% in the BCG group, and 88.1% and 4.9% in the early RC group, respectively with no significant difference in OS (p = 0.6) or CSM (p = 0.8) between the two groups. Among the patients treated with BCG, 5-yr HGR and progression rates were 41.9% and 17.4%, respectively; 39 patients (25%) underwent delayed RC after BCG. No significant difference in CSM emerged when comparing patients treated with delayed RC (after BCG) with those undergoing early RC (p = 0.86). ConclusionsOur findings suggest that intravesical BCG can be offered to patients as a resonable alternative to early RC for selected patients with VHR NMIBC. Patient summaryWe evaluated outcomes for patients with very high-risk non–muscle-invasive bladder cancer (NMIBC) treated with BCG (bacillus Calmette-Guérin) versus early surgical removal of the bladder and found no differences in survival. We conclude that BCG could be offered to selected patients with this type of bladder cancer as a reasonable alternative to early bladder removal.

Electromotive Drug Administration Chemotherapy with Mitomycin C Versus Bacillus Calmette-Guerin for the Treatment of Non-Muscle Invasive Bladder Cancer

BACKGROUND: Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment. OBJECTIVE: To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS). METHODS: Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up. RESULTS: Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419). CONCLUSIONS: No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.

Intravenous BCG Induction of Innate Memory in Young Pigs

Abstract Exposure to vaccine strain of Mycobacterium bovis(M. bovis), Bacillus Calmette-Guerin (BCG), alters innate immune cells through epigenetic and metabolic modifications resulting in heightened responses to subsequent microbial insult (innate memory). As a biomedical model for human disease, pigs provide a critical space to study the role of innate memory in disease resistance. Young pigs were inoculated intravenous (IV) or intraperitoneal (IP) with either live or heat-inactivated BCG (IV-live, IP-live, IV-inactive, noBCG groups). At 2wks post BCG inoculation, monocyte production of IL-1β nor TNF cytokines following ex vivostimulation with LPS was not different in any BCG group compared to noBCG, i.e. no innate memory. As dose of live BCG was lower than anticipated, at 3wks post primary inoculation, all pigs were inoculated a second time with respective preparations and routes of BCG. Ex vivocytokine production in LPS stimulated monocytes was measured again at 5wks post primary inoculation (2wks post-secondary inoculation) and both IL-1β and TNF cytokines were elevated in IV-live (innate memory), but not IP-live or IV-inactive groups. Additionally, ex vivostimulation of PBMC with homologous recall antigen (purified proteins from M. bovis) resulted in a 3-fold higher IFNγ response in IP-live compared to IV-live and no IFNγ production in noBCG or IV-inactive. Together these data suggest that while BCG can induce a state of innate memory in monocytes of young pigs, induction of training cannot be inferred by T cell production of IFNγ to recall protein antigen. Additionally, data continue to highlight pigs as a valuable model as multiple BCG factors (i.e. route, dose, or viability) may need to be considered for induction of innate memory. USDA-ARS CRIS project 5030-32000-225-000D

Manejo del carcinoma in situ de tramo urinario superior diagnosticado por biopsia ureteroscópica: ¿es el bacilo de Calmette-Guérin una alternativa a la nefroureterectomía?

IntroductionRadical nephroureterectomy (RNU) still represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, since the 1980s attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. MethodsThis retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with RNU, distal ureterectomy, or BCG instillations. Clinicopathological features and outcomes were compared between the RNU and BCG groups. ResultsA total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via a nephrostomy tube in 4 patients, a single-J ureteral stent in 5, and a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, with contralateral recurrence detected in four (50%), and 4 (13.8%) RUs underwent distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. ConclusionsAlthough RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

LBA02-04 OUTCOMES AND GENOMIC CHARACTERISTICS OF NEWLY DIAGNOSED HIGH GRADE TA PAPILLARY UROTHELIAL CARCINOMA TREATED WITH INTRAVESICAL CHEMOTHERAPY VS BACILLUS CALMETTE GUERIN (BCG): A COMPARATIVE STUDY DURING THE BCG SHORTAGE

You have accessJournal of UrologyCME1 Apr 2023LBA02-04 OUTCOMES AND GENOMIC CHARACTERISTICS OF NEWLY DIAGNOSED HIGH GRADE TA PAPILLARY UROTHELIAL CARCINOMA TREATED WITH INTRAVESICAL CHEMOTHERAPY VS BACILLUS CALMETTE GUERIN (BCG): A COMPARATIVE STUDY DURING THE BCG SHORTAGE Song Jiang, Manuel de Jesus E, Peter A. Reisz, Karissa Whiting, Carissa Chu, Wesley Yip, Andrew T. Lenis, Nicole Benfante, Eugene Cha, Timothy F. Donahue, Irina Ostrovnaya, Alvin Goh, Guido Dalbagni, Bernard H. Bochner, and Eugene J. Pietzak Song JiangSong Jiang More articles by this author , Manuel de Jesus EManuel de Jesus E More articles by this author , Peter A. ReiszPeter A. Reisz More articles by this author , Karissa WhitingKarissa Whiting More articles by this author , Carissa ChuCarissa Chu More articles by this author , Wesley YipWesley Yip More articles by this author , Andrew T. LenisAndrew T. Lenis More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Eugene ChaEugene Cha More articles by this author , Timothy F. DonahueTimothy F. Donahue More articles by this author , Irina OstrovnayaIrina Ostrovnaya More articles by this author , Alvin GohAlvin Goh More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Bernard H. BochnerBernard H. Bochner More articles by this author , and Eugene J. PietzakEugene J. Pietzak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Appropriate risk stratification of non-muscle invasive bladder cancer remains a central component of deciding treatment. Current criteria used to determine risk of disease recurrence and progression are based largely on historic cohorts before standardization of adjuvant intravesical treatments. The ongoing BCG shortage emphasizes the need for accurate contemporary data to best allocate BCG when supplies are limited. During periods of BCG shortage, our institution restricted BCG utilization to only those with HGT1 or carcinoma in situ (CIS), thus patients with HGTa without CIS were “naturally randomized” to receive either BCG or intravesical chemotherapy based on the time period of their initial diagnosis. METHODS: Retrospective review of an institutional database identified patients with newly diagnosed HGTa without CIS treated at MSKCC from 2017-2021. BCG restrictions were in effect between 01/19 and 04/20. Progression was defined as ≥T1 disease or radical cystectomy. The association of clinicopathologic variables and recurrence was performed with univariable Cox regression. Kaplan-Meier curves were used to visualize time to recurrence and progression. RESULTS: We identified 307 patients with papillary HGTa without CIS, 236 who were treated with BCG, and 71 with intravesical chemotherapy (N=60 mitomycin C, N=11 gemcitabine). Median follow up was 24 months for the BCG treated group, and 18 months from the chemotherapy treated group. There were no significant differences between the two groups regarding age, gender, tumor size, or tumor multiplicity. Targeted exon sequencing of pre-treatment tumors in 59 patients was performed and demonstrated no significant differences between treatment groups. Cumulative risk of high-grade recurrences was similar between the chemotherapy and BCG groups, with 86% vs 90% and 78% vs 82% recurrence-free survival at 6 and 12 months, respectively. Similarly, progression free survival was 89% at 12 months for both groups, but further follow up is needed. CONCLUSIONS: In this “naturally randomized” study, we report comparable clinical efficacy between chemotherapy and BCG immunotherapy, suggesting that intravesical chemotherapy is a reasonable alternative during the BCG shortage for patients with newly diagnosed HGTa without CIS. While our data is encouraging, there remains a critical need for better alternatives to BCG, especially for patients with higher risk non-muscle invasive bladder cancer. Source of Funding: NCI © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1187 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Song Jiang More articles by this author Manuel de Jesus E More articles by this author Peter A. Reisz More articles by this author Karissa Whiting More articles by this author Carissa Chu More articles by this author Wesley Yip More articles by this author Andrew T. Lenis More articles by this author Nicole Benfante More articles by this author Eugene Cha More articles by this author Timothy F. Donahue More articles by this author Irina Ostrovnaya More articles by this author Alvin Goh More articles by this author Guido Dalbagni More articles by this author Bernard H. Bochner More articles by this author Eugene J. Pietzak More articles by this author Expand All Advertisement PDF downloadLoading ...

MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37)

You have accessJournal of UrologyCME1 Apr 2023MP63-12 THE EFFECTS OF SEQUENTIAL MITOMYCIN AND BACILLUS CALMETTE-GUÉRIN TREATMENT VERSUS BACILLUS CALMETTE-GUÉRIN MONOTHERAPY IN PATIENTS WITH HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER: MITO-BCG (EUDRACT-2017-004540-37) Cosimo DE Nunzio, Costantino Leonardo, Antonio Carbone, Antonio Luigi Pastore, Riccardo Lombardo, Antonio Nacchia, Antonio Cicione, Beatrice Turchi, Giorgia Tema, and Andrea Tubaro Cosimo DE NunzioCosimo DE Nunzio More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Antonio CicioneAntonio Cicione More articles by this author , Beatrice TurchiBeatrice Turchi More articles by this author , Giorgia TemaGiorgia Tema More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Aim of our study was to evaluate recurrence free survival of sequential Mitomycin and Bacillus Calmette-Guérin (BCG) treatment versus BCG monotherapy in patients with High risk Non-Muscle Invasive Bladder Cancer. METHODS: MITO-BCG is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria: males with a diagnosis of High risk NMIBC (T1 tumor, G3, CIS, or multiple and recurrent and large (>3 cm) Ta, G1G2 tumors or patients in the last EAU recurrence category EAU/EORTC recurrence score ≥10), age >40 years and <75 years, ability of consent. Patients are randomized in two groups: first with BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with 81 mg Connaught strain BCG and second receiving BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before. Response will be assessed using cystoscopy and urine citology every 12 weeks for 2 years. Primary end points are recurrence rate; secondary end points are overall toxicity. RESULTS: The protocol study started on March 2019. Nowadays we enrolled 72 patients with a median age of 67 (IQR 59/73). Overall, 41 (57%) patients were randomized in the group of sequential combination therapy and 31 (43%) in the group of monotherapy with BCG. Mean Follow-up was 71±50 months. In BCG group 6/31 (19%) presented a recurrence while 10/41 (24 %) presented a recurrence in the combination group (p=0,611). On Cox regression analysis no differences were recorded in terms of recurrence when comparing both groups (HR: 1,23 95% CI: 0,46-3,50; p=0,640) (Figure). During follow-up only one patient experienced progression. Only 9 patients experienced adverse events with 8/9 grade I and one grade 4 (orchiectomy). No statistically significant differences were recorded in terms of complications between groups. CONCLUSIONS: The interim analysis of the Mito-BCG study suggests no differences in terms of recurrence free survival when comparing BCG alone vs sequential Mitomicin and BCG treatment. Both treatments present good and comparable tollerability. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cosimo DE Nunzio More articles by this author Costantino Leonardo More articles by this author Antonio Carbone More articles by this author Antonio Luigi Pastore More articles by this author Riccardo Lombardo More articles by this author Antonio Nacchia More articles by this author Antonio Cicione More articles by this author Beatrice Turchi More articles by this author Giorgia Tema More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparison of Sequential Intravesical Gemcitabine and Docetaxel vs Bacillus Calmette-Guérin for the Treatment of Patients With High-Risk Non–Muscle-Invasive Bladder Cancer

Due to the ongoing bacillus Calmette-Guérin (BCG) shortage, sequential intravesical gemcitabine and docetaxel has been increasingly used as first-line therapy for high-risk non-muscle-invasive bladder cancer (NMIBC). However, data directly comparing these 2 therapies are lacking. To compare the outcomes of patients with high-risk NMIBC treated with gemcitabine and docetaxel vs BCG. This retrospective cohort study was conducted from January 1, 2011, to December 31, 2021. The median (IQR) duration of follow-up was 23 (12-33) months for patients receiving gemcitabine and docetaxel and 49 (27-79) months for patients receiving BCG. All patients were treated at the University of Iowa tertiary care center. A total of 312 patients with high-risk treatment-naive NMIBC were included; 174 patients were treated with BCG therapy and 138 were treated with gemcitabine and docetaxel therapy. After undergoing complete transurethral resection of bladder tumor, patients received either sequential intravesical gemcitabine, 1 g, and docetaxel, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease free at the first follow-up visit. The primary outcome was high-grade recurrence-free survival (RFS). Survival probabilities were estimated using the Kaplan-Meier method. Cox regression models were used to evaluate the association of covariates with outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events, version 5. Among 312 patients, the median (IQR) age was 73 (66-79) years; 255 patients (81.7%) were male and 292 (93.6%) were White. Baseline clinicopathological characteristics such as sex, smoking status, and pretreatment tumor pathology were similar between treatment groups. High-grade RFS estimates were 76% (95% CI, 69%-82%) at 6 months, 71% (95% CI, 64%-78%) at 12 months, and 69% (95% CI, 62%-76%) at 24 months in the BCG group and 92% (95% CI, 86%-95%) at 6 months, 85% (95% CI, 78%-91%) at 12 months, and 81% (95% CI, 72%-87%) at 24 months in the gemcitabine and docetaxel group. Multivariable Cox regression analyses controlled for age, sex, treatment year, and presence of carcinoma in situ revealed that treatment with gemcitabine and docetaxel was associated with better high-grade RFS (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04) and RFS (hazard ratio, 0.56; 95% CI, 0.34-0.92; P = .02) than treatment with BCG. Induction therapy for BCG was associated with greater treatment discontinuation than induction therapy for gemcitabine and docetaxel (9.2% vs 2.9%; P = .02). In this cohort study, gemcitabine and docetaxel therapy was associated with less high-grade disease recurrence and treatment discontinuation than BCG therapy. These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines.

The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2—The results of ProBCG: a multicenter randomized clinical trial in Brazil

Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. A total of 264 volunteers were included for analysis (BCG=134 and placebo=130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60%×0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer

To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.

Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment

IntroductionThe objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and MethodsQuasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). ResultsOf the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). ConclusionsThere are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Calidad de vida en pacientes con tumor vesical no músculo-invasivo sometidos a tratamiento adyuvante intravesical

IntroductionThe objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and methodsQuasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). ResultsOf the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). ConclusionsThere are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.