Changes of urinary immunity and microbiome after intravesical BCG therapy and their association with outcomes in NMIBC.

Intravesical bacillus Calmette-Guerin (BCG) instillation is widely used as an adjuvant therapy after transurethral resection of bladder tumor (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not yet been clearly determined. We aimed to elucidate the relationship between dose, duration, and strain of BCG and clinical outcomes in NMIBC patients treated with TURBT. We conducted a literature search in Embase, Scopus, and PubMed databases for all relevant articles published up to October 2016 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The relative risks of clinical outcomes, including recurrence, progression, cancer-specific mortality, and all-cause mortality according to dose (standard vs low), duration (induction vs maintenance), and strain of BCG were presented as the pooled risk ratio (RR) and 95% confidence interval (CI). Nineteen studies meeting the inclusion criteria were finally selected in this meta-analysis. The risk of recurrence was significantly highly observed in case of low-dose BCG (RR, 1.17; 95% CI 1.06-1.30) and induction BCG (RR, 1.33; 95% CI 1.17-1.50) only group without heterogeneity among the included studies. Although there were no significant differences between dose or duration and other clinical outcomes. On direct comparison in each study comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01-1.64) and RIVM (RR, 2.04, 95% CI 1.28-3.25) strains. Funnel plot testing revealed no significant publication bias. The use of standard dose and maintenance BCG instillation may be effective to reduce recurrence rate after TURBT for NMIBC. Further large scale, well-designed, and prospective studies, with stratification of the patients into risk group at randomization, will be required to determine the optimal guideline of BCG use to improve clinical outcomes in NMIBC.

MAINTENANCE BACILLUS CALMETTE-GUERIN IMMUNOTHERAPY FOR RECURRENT TA, T1 AND CARCINOMA IN SITU TRANSITIONAL CELL CARCINOMA OF THE BLADDER: A RANDOMIZED SOUTHWEST ONCOLOGY GROUP STUDY

The Effect of Restaging Transurethral Resection on Recurrence and Progression Rates in Patients with Nonmuscle Invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guérin

MP01-19 UTILIZATION PATTERNS OF INTRAVESICAL BACILLUS CALMETTE-GUERIN THERAPY FOR PATIENTS WITH HIGH-GRADE, NON-MUSCLE INVASIVE BLADDER CANCER

MP08-07 THE IMPACT OF BLUE-LIGHT CYSTOSCOPY ON RESPONSE TO INDUCTION BCG IN PATIENTS WITH HIGH-GRADE NON-MUSCLE- INVASIVE BLADDER CANCER

A Territory-wide Study Investigating the Dose and Efficacy of Different Bacillus Calmette-Guérin Strains in Patients with Intermediate- and High-risk Non–muscle-invasive Bladder Cancer

MP71-19 ULTRASENSITIVE URINARY LIQUID BIOPSY ANALYSIS FOR BCG RESPONSE ASSESSMENT IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER

We evaluated the effect of intravesical Bacillus Calmette–Guerin (BCG) and BCG maintenance therapy on the prognosis of patients with T0 after repeat transurethral resection of bladder mass (TURBT). This retrospective analysis involved 427 patients who underwent repeat TURBT within 6 weeks after initial TURBT from 2007 to 2016. Repeat TURBT was performed in patients with high-risk criteria. Patients who achieved T0 after repeat TURBT did or did not receive intravesical BCG therapy. Patients were divided into three groups: non-BCG, BCG induction, and BCG maintenance groups. The study included 106 patients who achieved T0 after repeat TURBT. The median follow-up was 63 months. There were no significant differences in T stage among the three groups. High grade ratio (p = 0.001) and concomitant CIS ratio (p = 0.037) were significantly higher in the BCG maintenance than in the other two groups. The recurrence rates in the non-BCG, BCG induction, and BCG maintenance groups were 46.2%, 28.3%, and 19.2%, respectively (p = 0.043). Recurrence-free survival was significantly higher in the BCG maintenance group than in the BCG induction group (p = 0.032). Progression-free survival was also higher in the BCG maintenance group than in the BCG induction group, but the difference was not significant (p = 0.056). Multivariate Cox regression analysis showed that only intravesical BCG maintenance therapy was significantly associated with recurrence (hazard ratio 0.016, p = 0.016). In high risk NMIBC patients, intravesical BCG maintenance treatment is required even at T0 after repeat TURBT. Intravesical BCG maintenance therapy of patients with T0 after TURBT reduces recurrence.

The influence of immunocompromised status on recurrence and progression free survival among nonmuscle invasive bladder cancers (NMIBCs) undergoing transurethral resection of bladder tumor (TURBT) and adjuvant intravesical bacillus Calmette Guerin (BCG): Analysis of USA insurance claim data.

IntroductionInduction intravesical Bacillus Calmette-Guerin (BCG) followed by maintenance after transurethral resection of bladder tumor, is the standard adjuvant therapy for high-risk non-muscle invasive bladder cancer (NMIBC). There is sparse evidence on the practice of intravesical BCG in Australia. Our aim was to determine the outcomes of intravesical BCG therapy in NMIBC in Southwestern Sydney.MethodsThis was a multi-center retrospective audit of NMIBC patients who received intravesical BCG between January 2008 and June 2020. Data was collected across six tertiary hospitals in South Western Sydney. Primary outcome was disease-free survival (DFS). Secondary outcomes were overall survival (OS), BCG induction and maintenance rates.ResultsOf the 200 eligible patients over 12.5 years, median age was 77 years and 83% were male. Of these, 55%, 4.5%, 35% and 5% were Tis, Ta, T1 and unknown stage, respectively. All patients received induction BCG and 56% received maintenance BCG (range 3-36 months). Completion rate of induction BCG was 91%. Only 9% ceased treatment due to intolerance. The median duration of cystoscopy follow-up was 17 months. After a median follow-up time of 37 months, 55% developed recurrence (29% non-muscle invasive, 32% muscle-invasive disease, 8% distant metastasis). The 1-year and 5-year DFS rates were 72% and 41% (median DFS: 39 months). The 1-year and 5-year OS rates were 98% and 87% (median OS: not reached).ConclusionThe DFS and OS rates were comparable to previous literature. This provides real-world data to assist future clinical trials in NMIBC.

Introduction: The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) includes intravesical instillations of Bacillus Calmette-Guérin (BCG). Despite completing BCG therapy, up to 40 % of patients experience disease recurrence within five years. T cell exhaustion has been associated with poor outcome following treatment with BCG. In this study, we investigated whether T cell exhaustion, characterized by protein expression of PD-1 and PD-L1 in paired samples obtained before and after BCG treatment could provide further insight into BCG response and help predict outcome in patients with NMIBC. Methods: We included 105 patients with NMIBC, with transurethral resection of bladder tumor (TURBT) samples obtained prior to BCG (n=122) and after in cases with disease recurrence (n=44). Tissue sections from tissue microarrays (TMAs) were stained using immunohistochemistry to analyze the protein expression of the exhaustion markers PD-1 (clone EP239) and PD-L1 (clone 22C3). Data was analyzed using digital pathology software. Cells were scored as positive when detection of a nucleus was combined with a positive PD-1 or PD-L1 stain in both tumor or stromal area (defined by presence of positive pan-CK stain or not, respectively). In total, 167 samples were considered suitable for further analysis (cell count > 200 in tumor and stromal areas). Stratification of samples into high or low expression was based on a median split of the positive cell fraction. Results: When investigating the fraction of PD-1 and PD-L1 positive cells in the tumors, we observed that PD-1 expression significantly increased with tumor stage in pre- (p=0.002) and post-BCG (p=0.006) tumor samples. PD-1 expression was also increased in high-grade tumors compared to low-grade tumors in pre-BCG samples (p = 0.001). Furthermore, we observed a significant association between tumors of higher stage and high PD-L1 expression in the pre-BCG samples (p = 0.007). Patients with low expression of PD-1 and PD-L1 in the pre-BCG tumor samples had a superior high-grade recurrence-free survival (HG-RFS) compared to patients with high PD-1 (p=0.002) and PD-L1 (p=0.021) expression. In addition, low expression of PD-L1 in pre-BCG tumors was correlated with a better progression-free survival compared to the patients with high PD-L1 expression (p = 0.013). When creating a combined score with PD-1 high and PD-L1 high samples, we saw that these patients demonstrated a worse HG-RFS compared to patients with either mixed or low scores (p = 0.005). Conclusion: Protein expression of the exhaustion markers PD-1 and PD-L1 in pre-BCG tumor samples were correlated to higher stage and grade as well as worse HGFRS, indicating that T cell exhaustion plays an important role in resistance to BCG treatment and may be used to guide treatment. Citation Format: Tine G. Andreasen, Trine Strandgaard, Line Raaby, Jørgen Bjerggaard Jensen, Lars Dyrskjøt. High expression of the exhaustion markers PD-1 and PD-L1 in non-muscle invasive bladder cancer is associated with poor outcome following Bacillus Calmette-Guérin immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6479.

Repeat TURBT in large volume high-grade non-invasive bladder cancer

Background: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. Patients and Methods: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. Results: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. Conclusion: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

The bladder microbiota is not significantly altered by intravesical BCG therapy

This study aimed to comprehensively evaluate the prognostic value of T1 histo-anatomic substaging (T1a/T1b) for high grade (HG) non-muscle invasive bladder cancer (NMIBC) over a large single-centre cohort. Patients with primary HG T1 NMIBC were identified from our Institutional database, between 2011 and 2022. Data from diagnosis to repeated transurethral resection of bladder tumour (RE-TURBT), bacillus Calmette-Guérin (BCG) treatment and follow-up were collected. Patients were stratified based on histo-anatomic landmark into T1a (invasion above the Muscularis Mucosa-MM) and T1b (into/beyond MM). Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the impact of histo-anatomic substaging on recurrence-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS). Substaging was feasible in 88% of cases. The median (IQR) follow-up was 40 (17-72) months. T1b patients had larger initial tumours (> 3cm: 43.2% vs. 26.1%, p < 0.001), while upstaging to muscle-invasive bladder cancer (MIBC) at RE-TURBT was more frequent in T1b than in T1a (5.9% vs. 1.5%, p = 0.02). T1b patients without BCG induction had worse RFS and PFS (all p ≤ 0.02) compared to T1a, while no differences were observed in patients who received complete BCG induction. At Multivariate analysis, completing at least a BCG induction course was associated with better outcomes across all endpoints. Invasion of the MM in primary T1 NMIBC is associated with a higher risk of upstaging to MIBC. Patients who received full BCG induction had similar outcomes regardless of substaging, whereas T1b patients without BCG induction experienced higher recurrence and progression rates.