Maintenance Bacillus Calmette-Guerin Research Articles

Abstract PR005: Final results from a Phase I trial of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin (BCG) for patients with BCG-exposed high-grade non-muscle invasive bladder cancer

Abstract Background: Although retreatment with BCG is considered standard of care for patients with BCG-exposed high-grade (HG) non-muscle invasive bladder cancer (NMIBC), less than 50% of patients are expected to respond. As such, the ability to augment the efficacy of BCG in this population remains a critical unmet need. Preclinical studies suggest that intravesical gemcitabine (Gem) may demonstrate synergistic efficacy with BCG by favorably altering the tumor microenvironment. We therefore sought to evaluate the safety, tolerability, and preliminary clinical efficacy of GemBCG in patients with BCG-exposed HG NMIBC through an IRB-approved Phase I/II clinical trial. Methods: Patients with BCG-exposed papillary HG NMIBC (Ta/T1) with or without carcinoma in situ (CIS) that recurred within 24 months of BCG therapy were eligible for this trial. Exclusion criteria included BCG-unresponsive disease, contraindication to BCG therapy, or ureteral/urethral urothelial disease. Consenting patients underwent complete transurethral resection of bladder tumors followed by intravesical Gem twice weekly (weeks 1, 4, 7, 10) for a total of 8 doses. Dose escalation of Gem was performed from 50-2000 mg using a Bayesian modified continual reassessment method. Intravesical Gem instillations alternated with weekly intravesical TICE BCG therapy (weeks 2, 3, 5, 6, 8, 9) for a total of 6 doses fixed at 50 mg followed by maintenance BCG in responders. Complete response (CR) rates and progression to muscle-invasive bladder cancer (MIBC) or cystectomy were evaluated at 12 months of follow up in the Phase I cohort. Results: A total of 25 patients was enrolled (median age 70 years [IQR 64-75]), all of which have at least 12 months of follow up. Of these, 88% (22/25) were male. Median duration of bladder cancer treatment prior to enrollment was 385 days (IQR 173-634), and 28% (7/25) previously received either maintenance therapy (3/25) or >1 induction courses of BCG (4/25). Based on centralized pathology review, a total of 68% had CIS ± papillary disease (8 HGTa, 5 HGT1, and 4 Tis), while 32% had papillary-only disease (4 HGTa and 4 HGT1). No dose limiting toxicities were observed, and 14/25 patients were treated at the maximum tolerated dose. The treatment was well tolerated with no patient experiencing treatment-related Grade 3-5 toxicity. CR rates at 6 months and 12 months were 96% (24/25) and 92% (23/25), respectively. No progression to MIBC or radical cystectomy was observed. Conclusion: Combination GemBCG in BCG-exposed HG NMIBC is well tolerated and appears to provide excellent cancer control. Based on these encouraging findings and the ongoing phase II portion (NCT04179162), a prospective randomized controlled trial comparing GemBCG to BCG alone for BCG-exposed NMIBC is planned through the National Clinical Trial Network (Alliance A032303). Citation Format: Syed M. Alam, Christopher D. Gaffney, Jessica Lavery, Merve Basar, Neeta D'Souza, Christian Hernandez, Melissa McCarter, Patricia Moran, Kristen Stasi, Kara Worth, Daniel Sjoberg, Guido Dalbagni, Timothy Donahue, Sherri Donat, Dean Bajorin, Bernard H. Bochner, Alvin Goh, Judy Sarungbam, Hikmat Al-Ahmadie, Eugene J. Pietzak. Final results from a Phase I trial of intravesical chemoimmunotherapy with gemcitabine and Bacillus Calmette-Guérin (BCG) for patients with BCG-exposed high-grade non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr PR005.

Abstract B007: Urinary cytokine profiles reflect rationale for treatment with gemcitabine and Bacillus Calmette-Guérin (BCG) in BCG-exposed high-risk non-muscle invasive bladder cancer (NMIBC)

Abstract Background: Bacillus Calmette-Guérin (BCG) remains the most efficacious and widely studied intravesical therapy for NMIBC, but less than 50% of BCG-exposed patients will respond to a second course of BCG. One mechanism of resistance to BCG is an immunosuppressive tumor microenvironment with myeloid-derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), and Tregs that abrogate the anti-tumor immune response. IL-6 is associated with MDSCs and BCG resistance. Gemcitabine (Gem), however, has been shown to selectively inhibit MDSCs, TAMs, and Tregs. This observation served as the biologic rationale for our recently completed Phase I trial of combination chemoimmunotherapy with intravesical Gem and BCG for BCG-exposed high-grade (HG) NMIBC (NCT04179162) that demonstrated excellent tolerability and preliminary efficacy (96% complete response at 6-month follow-up). We sought to evaluate immune modulation with the addition of Gem to BCG as determined by changes in urinary cytokine/chemokine levels. Methods: Patients with BCG-exposed papillary HG NMIBC (Ta/T1) +/- carcinoma in situ recurring within 24 months of BCG therapy were treated with intravesical Gem twice weekly (weeks 1,4,7,10; 8 total doses) and intravesical TICE BCG weekly (weeks 2,3,5,6,8,9; 6 total doses) followed by SWOG maintenance BCG for responders. Urine specimens were collected prior to treatment and on weeks 4, 8, 12, 24, and 52 weeks after on-trial treatment initiation. Urinary cytokines present in the supernatant were evaluated using a 96-plex immuno-oncology proximity extension assay (Olink®). Cytokines with < 75% of values below the lower limit of detection of the assay were not evaluated. We performed an exploratory analysis of select pre-specified cytokines using a linear mixed model. Mean changes and 95% confidence intervals (CI) are presented with global p-values testing for a change in cytokine levels at any timepoint. Results: Urine samples were available for all 25 patients in the Phase I study. A total of 25 proteins on the panel were excluded due to low detection. Chemokines associated with T-cell trafficking (CXCL9, CXCL10, CXCL11) increased during induction treatment through 3 months of follow up and then returned to baseline after the completion of treatment (p<0.001 for each cytokine). IL-6 decreased after initiation of treatment and remained low through 12 months of follow up (-2.7, 95% CI -3.8, -1.7; p<0.001). Notably, the one patient who had a recurrence also had a rise in IL-6 after an initial decline while on treatment. Conclusion: We found evidence that the addition of intravesical gemcitabine to BCG favorably augments the tumor microenvironment based on changes in urinary cytokine/chemokine profiles. Additional tumor and urinary correlatives are ongoing. Based on the the robust preliminary efficacy demonstrated in the ongoing phase I/II trial (NCT04179162), a prospective randomized controlled trial comparing GemBCG to BCG alone for BCG-exposed NMIBC is planned through the National Clinical Trial Network (Alliance A032303). Citation Format: Christopher D. Gaffney, Syed M. Alam, Jessica A. Lavery, Merve Basar, Neeta D'Souza, Christian Hernandez, Melissa McCarter, Patricia Moran, Kristen Stasi, Kara Worth, Daniel Sjoberg, Guido Dalbagni, Timothy Donahue, Sherri Donat, Dean Bajorin, Bernard H. Bochner, Alvin Goh, Judy Sarungbam, Hikmat Al-Ahmadie, Eugene J. Pietzak. Urinary cytokine profiles reflect rationale for treatment with gemcitabine and Bacillus Calmette-Guérin (BCG) in BCG-exposed high-risk non-muscle invasive bladder cancer (NMIBC) [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B007.

Efficacy of BCG for non-muscle invasive bladder cancer following nephroureterectomy for upper tract urothelial carcinoma

PurposeTo evaluate the efficacy of intravesical (IVe) Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer (NMIBC) recurrences in patients who have previously undergone nephroureterectomy for upper tract urothelial carcinoma (UTUC). MethodsWe performed a single institution retrospective review of patients who underwent nephroureterectomy for UTUC from 2009 to 2021. Patients who subsequently developed NMIBC treated with transurethral resection followed by IVe BCG were included in the study group. A control cohort was formed by retrospective review of patents with primary NMIBC treated with BCG during the same period. Patients in the control cohort were matched by stage of bladder cancer at a 2:1 ratio of control to study subjects. Demographic data, pathology of bladder tumors prior to and following BCG, use of maintenance BCG (mBCG), time to recurrence, time to progression, progression to cystectomy, and progression to metastatic disease were collected on all patients. Descriptive statistics were utilized to compare the 2 groups. The primary outcome was progression to muscle invasive disease. Secondary outcomes included intravesical recurrence free survival, disease free survival, and progression to metastatic disease. Univariable and multivariable logistic regression analysis was performed to elucidate independent variables associated with bladder tumor recurrence. Multivariable Cox regression analysis was used to assess the impact of prior UTUC on time to bladder tumor recurrence. ResultsOne-hundred and ninety-one patients underwent nephroureterectomy at our institution from 2009 to 2021 for UTUC. Twenty-five patients were identified to have subsequently developed NMIBC recurrences treated with inductions BCG. The control group was comprised of 50 patients with primary NMIBC matched by stage of bladder cancer for which BCG was indicated in the study group. Median (interquartile range [IQR]) follow-up was significantly longer in the control group relative to the study group (64.8 [50.1-85.6] vs 25 months [17-35]; P = 0.001). There were no significant differences in demographics between the study and control groups. The rate of progression to muscle invasive disease was 17% vs 0% in the study group and control group respectively (P = 0.0521). History of UTUC was associated with increased risk of intravesical bladder tumor recurrence post BCG on multivariable analysis (HR 2.5; P = 0.017) and Kaplan Meier survival analysis (P = 0.039). The mean time to bladder tumor recurrence after treatment with BCG was significantly worse in the study group at (7.9 vs. 23.9 months; P = 0.0322). Similarly, the rate of progression to metastatic disease was worse in the study group (24% vs 2%; P = 0.0047). Overall disease-free survival was also noted to be significantly worse on Kaplan Meier survival analysis in the study group (P = 0.0074). No statistically significant differences in the stage grade of bladder tumor recurrence, grade of bladder tumor recurrence, or rate of progression to cystectomy were identified. ConclusionsOur study suggests reduced efficacy of BCG for NMIBC in patients with a history of UTUC. Patients in this population should be counseled accordingly. Research into alternative treatments for bladder tumor recurrence and more aggressive prophylactic regimens after nephroureterectomy for prevention of bladder tumor recurrence in this population is encouraged.

BladderGATE: Atezolizumab + intravesical BCG (bacillus Calmette-Guerin) upfront combination in patients with high risk non-muscle invasive bladder cancer (NMIBC)—Phase I-II ONCOSUR study.

595 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection is the current standard of care for patients (pts) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years and 5 years are around 30-40% and 70-80% respectively. Atezolizumab is a IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (MS. van der Heijden . Eur Urol 2021) and for pts with unresponsive NMIBC (PC. Black . Eur Urol 2023) with excellent results. Atezolizumab in combination with standard BCG could provide synergistic benefit for pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study which evaluates the safety and efficacy of upfront atezolizumab + intravesical BCG in pts with high-risk NMIBC. Methods: Pt had confirmed histopathology of high-risk NMIBC, BCG naïve or stopped >2 years ago, WHO PS 0-2 and adequate hematologic and organ function. Dose-escalation design to identify DLT and MTD (9 pts) and to evaluate safety and efficacy in an expansion cohort (30 pts) were programed. Pt received six weekly induction instillations, and maintenance instillations at 3, 6 and 12 months + intravenously atezolizumab 1200 mg every 3 weeks, up to 1 year. Urine/blood and tissue samples were collected for translational and biomarker correlative study. Primary objective is disease free survival. Secondary objectives include safety profile and quality of life. Results: Finally 36 pt were included, median age 70 years, 86% men, 61% of pt were former smokers, 22% smokers and 17% had never smoked, and tumor size was ≥3 cm in 44% of pt. With a 22 months median follow-up, 56% of pt had completed BCG treatment and 89% had received adequate BCG treatment (5 induction plus at least 2 maintenance instillations). Thirteen pts discontinued atezolizumab due to immune-related AEs (7 pts) (g2 dermatitis, g3 hepatitis, encephalitis, pneumonitis, myocarditis, adrenal insufficiency and psoriasis), due to early-relapse disease (3 pts) and progressive-disease (3 pts). All irAEs were solved and no toxic death were reported. Of the 36 pts analyzed, 6 pts showed local recurrence (17%), 5 pts with high-risk NMIBC (14%) and 1 pt with low-risk NMIBC, 1 pt with UTUC, and 3 pts with local muscle invasive bladder cancer progressive-disease (8 %). Preliminary 2-year disease free survival is 72.8% (95% CI: 56.1% - 89.5%). Conclusions: The combination strategy of atezolizumab + intravesical BCG upfront in high-risk NMIBC pts appears feasible and safe. A 14% of 2-years local recurrence-rate and 8% of local progressive-disease are promising results, pending to randomized Ph3 ALBAN study data (GETUG). Supported by Roche-Spain. Clinical trial information: NCT03425201 .

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

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

A Rare Case Seen in a Patient with Intravesical Bacillus Calmette-Guerin (BCG) Intolerance: Autoimmune Myopathy

Aim: We present a case of autoimmune myopathy observed in a patient who developed intolerance
 to intravesical Bacillus Calmette-Guerin (BCG), which is used in the treatment of non-muscle invasive
 bladder cancer.
 Case: Intravesical BCG, which is used for the treatment of non-muscle invasive bladder cancer, probably
 effects by increasing autoimmunity in the bladder. This increased autoimmunity sometimes causes local
 or systemic reactions. In this case report, we would like to present a 61-year-old male patient who
 developed intolerance while taking the first dose of maintenance BCG, and then on-going treatment
 was stopped. The patient had convulsive painful cramps and muscle twitches in the left quadriceps
 femoris region one month later BCG intolerance. When the patient’s anamnesis, electromyography
 (EMG) results, elevated Creatine Kinase value and other laboratory data were evaluated together, BCG
 triggered autoimmune myopathy was considered. Therefore, steroid treatment was started and the
 patient recovered seven weeks later. This is a rare case of autoimmune myopathy in a patient who
 received intravesical BCG therapy for a bladder tumor.
 Conclusion: The case of BCG-associated autoimmune myopathy is extremely rare. When this situation
 is suspected, it is beneficial to start steroid treatment without delay.

Atezolizumab + intravesical BCG (bacillus Calmette-Guerin) upfront combination in high risk non–muscle- invasive bladder cancer (NMIBC) patients: Safety interim report of BladderGATE phase I-II study.

e16590 Background: Intravesical Bacillus Calmette-Guerin (BCG) induction + BCG maintenance after transurethral resection (TURBT) is the current standard of care for patients (pt) with high-risk non-muscle invasive bladder cancer (NMIBC). Recurrence rate at 2 years is around 30%, which is clearly unsatisfactory. Atezolizumab is a humanized IgG1 monoclonal antibody targeting PD-L1 and is associated with long-term durable remissions in pts with metastatic urothelial cancer (Powles T. Lancet. 2018). Pembrolizumab (KN-057-FDA approved) and Atezolizumab (SWOG S-1605 Ph2 study) were recently evaluated for pts with unresponsive NMIBC ineligible for radical cystectomy with excellent results. Atezolizumab in combination with standard BCG could provide synergistic benefit for pts with NMIBC. BladderGATE (NCT04134000) is a phase Ib-II study which evaluates the safety and efficacy of Atezolizumab + intravesical BCG in pts with high-risk NMIBC. Methods: Pt had confirmed histopathology of high-risk NMIBC, BCG naïve or stopped > 2 years ago, WHO PS 0-2 and adequate hematologic and end-organ function. De-escalation design to identify DLT and MTD to evaluate safety and efficacy in an expansion cohort. Pt will receive induction BCG, 1 instillation every week (qw) (dose level 0) or BCG, 1/2 instillation qw (dose level -1) + intravenously atezolizumab 1200 mg every 3 w (q3w), during 6 w. After induction, BCG was administered at weeks 13-15, 25-27 and 49-51 and atezolizumab up to 1 year. Pt were accrued to each dose level in cohorts of 10 pt until the MTD is achieved (dose at which < 4 out of 10 pt experience DLT). DLT was evaluated during induction treatment. Additional pt will be included in the expansion cohort. Results: 34 pt are included in this interim analysis, median age 70 years, 82% men, 82% ECOG 0 and 79% had previous transurethral resection. Median treatment exposure was 28 weeks. No DLTs were reported in the first 10 patients included in dose level 0. Most frequent adverse events (AEs) all grades were: asthenia (24%), pruritus (21%), pyrexia (18%), hypothyroidism (15%), urinary tract infection (15%), hyperthyroidism (9%), hypertransaminitis (9%), back pain (9%), myalgia (9%) and dysuria (9%). Most frequent AES G 3-4 were mainly IRAEs: myocarditis (3%), asthenia (9%), immune-mediated hepatitis (3%), hyponatremia (3%), encephalopathy (3%) and Guillain-Barre syndrome (3%). Two patients discontinued study treatment due to immuno-mediated hepatitis Grade 3 and immuno-mediated pneumonitis Grade 3 respectively. Conclusions: Induction treatment with BCG + atezolizumab followed by maintenance treatment seems to be feasible and have a manageable toxicity profile. The toxicity of BCG and atezolizumab appears not to be enhanced in this combination. Clinical trial information: NCT04134000 .

Study of real-world treatment patterns and adherence to bacillus Calmette-Guerin (BCG) in the context of guideline recommendations for patients with high-risk non-muscle invasive bladder cancer (NMIBC).

470 Background: Intravesical BCG is considered a first-line (1L) treatment for high-risk NMIBC patients. Since the presence of carcinoma in situ (CIS) in NMIBC is associated with increased disease progression rates and poor clinical outcomes, BCG is prioritized in clinical guidelines for NMIBC patients with CIS. However, BCG’s US shortage may negatively affect clinical outcomes in patients. This study evaluated the adequacy of BCG treatment patterns among NMIBC patients, including a subgroup with CIS. Methods: Adults with NMIBC treated with BCG were selected from de-identified IBM MarketScan Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Treatment patterns were assessed from the first BCG claim (triggering the start of 1L treatment) until the end of the patient’s observation. Consistent with real-world literature, adequate BCG induction was defined as ≥5 BCG claims within 70 days of the first BCG claim whereas adequate BCG induction and maintenance was defined as ≥7 BCG claims within 274 days of the first BCG claim. Proportions of patients with adequate BCG induction and maintenance were compared between CIS subgroup and overall NMIBC cohorts using chi square tests. Results: Of 5,803 NMIBC patients treated with 1L BCG, 1,182 (20.4%) had documentation of CIS. Overall and CIS cohorts had similar mean age (67 years; range 18-101 years). After 1L BCG, 56.6% and 71.8% of the overall and CIS cohorts had another treatment (P<.001; table). While 86.9% and 90.0% of the overall and CIS cohorts had adequate BCG induction (P=0.003), only 41.5% and 50.8% had adequate BCG maintenance (P<.001). More patients in the CIS versus overall cohort had a cystectomy (13.9% vs 9.7%; P<.001). Conclusions: In this study, most NMIBC patients treated with BCG received adequate induction; however, BCG maintenance was inadequate and most patients had another treatment following 1L BCG. Patients with CIS were more likely to have cystectomy after BCG, suggesting higher risk of progression in this subgroup. Results of this study further emphasize a need for additional available treatment options that are safe, efficacious, and tolerable. [Table: see text]

A phase II trial of intravesical chemoimmunotherapy with gemcitabine and bacillus Calmette-Guérin (BCG) for patients with BCG-exposed, high-grade, non-muscle–invasive bladder cancer.

TPS579 Background: The standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after exposure to induction only BCG or relapse >12 months after “adequate” BCG is retreatment with BCG. However, ~50% of patients will relapse within 6 months. Thus, there is a critical need to develop novel combination therapies to improve BCG immunotherapy efficacy. Combination BCG with immune checkpoint inhibition is associated with a ~12-18% risk of serious treatment-related adverse events and BCG combined with Mitomycin C (MMC) has unacceptable urinary toxicity. Intravesical Gemcitabine (GEM) is a common treatment for NMIBC, is well tolerated, has better efficacy after BCG than MMC, and, based on preclinical data, may synergistically enhance the efficacy of BCG by augmenting the immune tumor microenvironment. We completed a prospective Phase I trial of chemoimmunotherapy with gemcitabine and BCG in BCG-relapsed/BCG-exposed NMIBC that was well-tolerated (no treatment related grade ≥3 adverse events) with promising early efficacy (95% [19/20] 6-month complete response rate). No dose limiting toxicities were seen. The maximum tolerated dose (MTD) was 2000 mg gemcitabine and 50 mg TICE BCG. Methods: To address the need for more effective and less toxic bladder preserving treatment options by enhancing the effectiveness of BCG, we launched an investigator-initiated phase I/II trial of combination intravesical gemcitabine with BCG in patients with BCG-exposed NMIBC (NCT04179162). The Phase II portion is currently enrolling patients with BCG-exposed carcinoma in-situ (CIS ±Ta/T1) that recurred within 24 months of last BCG (BCG-exposed/BCG-relapsing NMIBC). Patients with BCG-unresponsive disease, contraindication to BCG, or prostatic/ureteral urothelial disease are excluded. Induction intravesical GEM (2000mg, twice weekly) is given weeks 1, 4, 7, and 10 and intravesical BCG (40mg, Tice strain, weekly) is given weeks 2, 3, 5, 6, 8, and 9. Responders receive SWOG maintenance BCG. The primary endpoint is clinical complete response (CR) at 6 months (absence of high-grade disease on cystoscopy/TURBT and negative cytology) using a Simon’s optimal 2-stage design testing the null hypothesis of a true CR of 55% at 6 months (based on historical outcomes of BCG alone) against a 1-sided alternative. In the first stage, the study would stop if ≤ 9/15 patients had a CR. In the second stage, the null hypothesis will be rejected if ≥ 29 CRs are observed in 43 total patients (type I error rate 5% and power of 80% if the true CR rate is 75%). Phase I patients treated at the MTD (14/25) are included in Phase II. Secondary outcomes include recurrence-free, progression-free, and cystectomy-free survival. Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. Clinical trial information: NCT04179162 .

Time to event following bacillus Calmette-Guerin therapy initiation in Medicare beneficiaries with intermediate- to high-risk non-muscle invasive bladder cancer, 2010-2019.

473 Background: For patients with intermediate- to high-risk non-muscle invasive bladder cancer (NMIBC), standard of care includes transurethral resection (TURBT) followed by induction and maintenance intravesical immunotherapy with Bacillus Calmette-Guerin (BCG). This study describes characteristics and clinical outcomes of Medicare beneficiaries newly diagnosed with NMIBC who initiated BCG therapy following TURBT. Methods: Retrospective cohort study using Centers for Medicare and Medicaid-sourced Medicare Fee-for-Service medical/pharmacy claims (100% sample). Patient selection criteria: ≥1 bladder cancer diagnosis 2010-2019, no prior radiotherapy, systemic therapy, cystectomy, or metastasis in 6 months post-diagnosis, continuously enrolled in Medicare ≥12 months pre- and post-index (or death). Index date = date of first BCG instillation. A literature-based definition for adequate maintenance BCG defined adequate (≥7 instillations of BCG within 274 days of BCG initiation) and inadequate (remainder) BCG therapy for patient stratification. Events: time to BCG discontinuation, radical cystectomy, systemic therapy, radiation, and metastasis. Provider access to BCG (due to supply shortage), patient tolerability, and NMIBC risk status are not captured in claims data. Results: Of 46,052 BCG-treated patients eligible for analysis, 19,859 (43.1%) received adequate BCG therapy. The two cohorts had similar baseline characteristics (Table) and median duration of follow up (46 months). Median (interquartile range [IQR]) time from NMIBC diagnosis to BCG initiation was 2.8 (8.2) months for adequate, 3.7 (14.4) months for inadequate BCG. Time from BCG initiation to discontinuation, radical cystectomy, systemic therapy, radiation, and metastasis are reported in the table. Conclusions: Between 2010 and 2019, 57% of Medicare patients initiating BCG following diagnosis of NMIBC and TURBT may not have received adequate BCG therapy. Patients with inadequate BCG therapy had numerically shorter time to radical cystectomy, systemic therapy, radiation, and metastasis than those with adequate BCG therapy. Characteristics & Outcomes by Cohort. [Table: see text]

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study

BackgroundNovel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients. ObjectiveTo evaluate the safety and preliminary efficacy of anti–PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). Design, setting, and participantsA multicenter phase 1 trial was conducted at community and academic sites. InterventionPatients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). Outcome measurements and statistical analysisPost-treatment cystoscopy and urine cytology were performed at 3 and 6 –mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. Results and limitationsTwenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. ConclusionsD combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. Patient summaryDurvalumab combination therapy can be safely administered to non–muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Fremantle protocol: Multicenter clinical outcomes for a pragmatic protocol for intravesical bacillus Calmette-Guerin.

To examine the utility and efficacy of a multifaceted protocol for the administration of intravesical bacillus Calmette-Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC). A multicenter retrospective review was conducted among 83 patients undergoing Fremantle protocol intravesical BCG for NMIBC within 4 major hospitals in Western Australia between January 2016 and December 2018. The Fremantle protocol consists of weekly BCG instillations for 6 weeks during the induction phase, followed by monthly BCG instillations for 10 months during the maintenance phase with integrated clearance-to-proceed algorithms for urine MSU checks, flexible cystoscopies performed at 3 monthly intervals during maintenance BCG, and repeat GA cystoscopies with four quadrant bladder biopsies routinely obtained following the completion of induction and maintenance treatment. For patients undergoing Fremantle protocol BCG, 98.8% (82/83) and 75.9% (63/83) of patients completed their induction and maintenance courses of BCG, respectively. Induction BCG was delivered over a median duration of 35 days (range 34-84 days), and maintenance BCG was delivered over a median duration of 266 days (range 1-682 days). The tumor recurrence rate was 10.8% (9/83) at the time of post-induction biopsies, 2.4% (2/83) during maintenance treatment, 0% (0/60) at the time of post-maintenance biopsies, and 8.8% (5/57) after a median further follow-up of 16 months (range 0-51 months). The Fremantle protocol appears to be a safe and effective BCG regimen with several advantages over other BCG protocols, including high completion rates, low recurrence rates, and being highly pragmatic.

Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America, Europe and Asia: A real-world data analysis.

BackgroundThis study examined real-world treatment and management of bacillus Calmette-Guérin (BCG)-unresponsive patients across 3 continents, including patients unable or unwilling to undergo cystectomy.Materials and methodsPhysicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy (in Japan, physicians provided a total of 5 patients across both cohorts).ResultsMost patients had received 1 (37%) or 2 (24%) maintenance courses of BCG. Five or more maintenance BCG courses were received by patients in Japan (59%) and China (31%), while in Germany 76% of patients received only 1 course. Most patients became BCG-unresponsive during their first (44%) or second (22%) treatment course; in Germany, 77% became BCG-unresponsive during their first treatment course. Most countries did not provide another course of BCG after a patient first became unresponsive, whereas unresponsive patients in Japan and China were most likely to be retreated with BCG. “Untreated - on watch and wait” was the main treatment/management approach received post-BCG treatment for 42% or more of patients in most countries except China (39%) and the United States (36%). “Following treatment guidelines” was consistently the top reason for post-BCG treatment selection across all treatment options.ConclusionsThis study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer, and found that many patients experienced periods of no treatment after not responding to BCG therapy.

Oncologic outcomes of Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer: A meta-analysis.

There is a challenge on the medical efficacy of intravesical Bacillus Calmette-Guérin (BCG) therapy and the power of the immune system boosting, which can be influenced by the age of the non-muscle-invasive bladder cancer (NMIBC) patients. This meta-analysis evaluates the efficacy of BCG therapy among aged (>70) and younger patients with non-muscle-invasive bladder cancer (NMIBC). The central database of PubMed, Scopus, and Web of Science were queried until August 4, 2021, by using "BCG," "Bladder Cancer," "AGE," and "efficacy" keywords. After excluding duplicated results, titles and abstracts were evaluated by two independent reviewers. The exclusion criteria included non-English studies, conference abstracts, reviews, editorials, letters, and comments. Three main outcomes, disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS), were considered. The statistical analysis was performed using STATA (version 14; Stata Corp, College Station, Texas, USA). From 1115 found documents, the 24 research articles were recruited in the systematic review, and 10 were the candidate for meta-analysis. The overall estimate of H.R. revealed that BCG therapy in those over age 70 is significantly associated with an improved risk of progression and cancer-specific death in studied patients. However, this association was not statistically significant for DFS (1.04 (95% CI: 0.85,1.26)). The BCG maintenance therapy improved CSS and PFS oncological outcomes in elderly patients with NMIBC. BCG therapy did not significantly change the DSF.

MP59-06 PD-L1 EXPRESSION AND BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 May 2022MP59-06 PD-L1 EXPRESSION AND BCG RESPONSE IN NON-MUSCLE INVASIVE BLADDER CANCER Solomon Woldu, Thomas Gerald, Vitaly Margulis, Daniel Halstuch, Yaara Ber, Karin Lifshitz, David Margel, Yair Lotan, and Liwei Jia Solomon WolduSolomon Woldu More articles by this author , Thomas GeraldThomas Gerald More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Daniel HalstuchDaniel Halstuch More articles by this author , Yaara BerYaara Ber More articles by this author , Karin LifshitzKarin Lifshitz More articles by this author , David MargelDavid Margel More articles by this author , Yair LotanYair Lotan More articles by this author , and Liwei JiaLiwei Jia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002642.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical bacillus Calmette Guerin (BCG) is the standard of care adjuvant therapy for high risk non-muscle invasive bladder cancer (NMIBC), yet many patients experience recurrence or disease progression. The mechanism of BCG is thought to be related to stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. We sought to determine the association between PD-L1 expression and BCG treatment. METHODS: We identified 102 BCG-naïve patients with high grade (HG) NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR). Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score > 0. BCG unresponsiveness was defined by presence of HG disease at 6 months following adequate BCG (one induction and maintenance cycle or two induction cycles) for pT1 or 12 months for CIS or presence of pT1 at 3 months after induction. HG relapse was defined as HG disease after being followed for 6 months after BCG. RESULTS: The median follow-up was 57 months. Median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate reinduction BCG. PD-L1 expression was observed in 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS. BCG unresponsiveness and HG relapse were observed in 32 (35.6%) and 29 (34.5%), respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR=0.11; 95% CI 0.01-0.90) but not HG relapse (OR=0.30; 95% CI 0.06-1.44). The sensitivity, specificity, positive predictive value, and negative predictive value of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. PD-L1 positive patients had a post-test probability of BCG responsiveness of 93%. On multivariate regression, pT1 (OR = 0.16; 95% CI 0.05-0.60), CIS (OR=0.25; 95% CI 0.07-0.86), and PD-L1 expression (OR=15.63; 95% CI 1.78-142.86) were associated with BCG responsiveness. CONCLUSIONS: PD-L1 expression in HG NMIBC was low, and those with PD-L1 expression at initial TUR were more likely to harbor invasive disease. Patients with PD-L1 expression were more likely to demonstrate BCG responsiveness. These findings suggest a role of PD-L1 in the immune surveillance mechanism of BCG at initial diagnosis and may assist in predicting response to BCG in patients with HG NMIBC. Further investigation is needed to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1003 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Solomon Woldu More articles by this author Thomas Gerald More articles by this author Vitaly Margulis More articles by this author Daniel Halstuch More articles by this author Yaara Ber More articles by this author Karin Lifshitz More articles by this author David Margel More articles by this author Yair Lotan More articles by this author Liwei Jia More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD-L1 expression and BCG response in nonmuscle invasive bladder cancer.

545 Background: Intravesical bacillus Calmette Guerin (BCG) is the standard of care adjuvant therapy for high risk non-muscle invasive bladder cancer (NMIBC), yet many patients experience recurrence or disease progression. The mechanism of action of BCG is believed to be related to stimulation of immune surveillance. Relatedly, systemic immune checkpoint inhibition is currently being utilized in advanced bladder cancer and approved for BCG unresponsive NMIBC. We sought to determine the association between PD-L1 expression and BCG treatment. Methods: We identified 102 BCG-naïve patients with high grade (HG) NMIBC treated with BCG. All patients underwent initial transurethral resection (TUR) for pathologic diagnosis. Dako 22c3 assay was used to determine PD-L1 expression. Patients were defined as PD-L1 positive if the combined positive score (CPS) > 0. BCG unresponsiveness was defined by presence of high grade disease at 6 months following adequate BCG (one induction and maintenance cycle or two induction cycles) for pT1 or 12 months for CIS or presence of pT1 at 3 months following induction. HG relapse was defined as presence of any HG disease after being followed for 6 months after BCG. Results: The median follow-up time was 57 months. Median number of BCG maintenance cycles was 1, and 17 (16.7%) patients underwent immediate reinduction BCG. PD-L1 expression was observed 5.9% of pTa, 30.0% of pT1, and 3.6% of CIS. BCG unresponsiveness and HG relapse were observed in 32 (35.6%) and 29 (34.5%) patients, respectively. On univariate analysis, PD-L1 expression was inversely associated with BCG unresponsiveness (OR = 0.112; 95% CI 0.014-0.898) but not high grade relapse (OR = 0.296; 95% CI 0.061-1.440). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression for BCG responsiveness were 22%, 97%, 93%, and 41%, respectively. The post-test probability of BCG responsiveness was 93% in patients positive for PD-L1 based on a positive likelihood ratio of 7.33 for PD-L1 expression. On multivariate regression, pT1 (OR = 0.159; 95% CI 0.045-0.600), CIS (OR = 0.247; 95% CI 0.071-0.857), and PD-L1 expression (OR = 15.625; 95% CI 1.779-142.857) were independently associated with BCG responsiveness. Conclusions: PD-L1 expression in HG NMIBC was low, and patients with PD-L1 expression at initial TUR were more likely to harbor invasive disease. Patients showing PD-L1 expression were more likely to demonstrate BCG responsiveness. These findings suggest a role of PD-L1 in the immune surveillance mechanism of BCG at initial pathologic diagnosis and may assist in predicting responses to BCG among patients with HG NMIBC. Further investigation is required to determine if additional immune checkpoint markers have strong correlation with BCG response, particularly among patients without PD-L1 expression.

Compared Efficacy of Adjuvant Intravesical BCG-TICE vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis.

Simple SummaryIntravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer. Different BCG strains are currently available and the superiority of any BCG strain over another could not be demonstrated yet. We compared the efficacy of two BCG strains: RIVM and TICE, respectively. In this propensity-score matched cohort study, we showed no particular survival benefit of TICE vs RIVM in the case of high-risk disease. Nevertheless, stratifying our data for re-staging procedures and for those who received BCG maintenance, we identified BCG TICE to improve RFS independently. Herein, we corroborated the importance of performing a routine secondary resection followed by an adequate maintenance course of BCG. Future larger prospective randomized head-to-head trials are needed to further elucidate this important topic, especially in this era of BCG shortage.Background: Intravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan–Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24–77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan–Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25–0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non–muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14

BackgroundVPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. ObjectiveTo report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non–muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. Design, setting, and participantsWe designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. InterventionPatients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. Outcome measurements and statistical analysisThe primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. Results and limitationsAfter exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1–64.4%) and remained at 47.4% (95% CI 30.4–62.6%] at 2 yr and 43.7% (95% CI 26.9–59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. ConclusionsAt 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. Patient summaryWe conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non–muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

MP16-06 A NOVEL NOMOGRAM TO PREDICT BCG RESPONSE IN PATIENTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Non-invasive II (MP16)1 Sep 2021MP16-06 A NOVEL NOMOGRAM TO PREDICT BCG RESPONSE IN PATIENTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER Kelly Bree, Patrick Hensley, Nathan Brooks, Lianchun Xiao, Yu Shen, Neema Navai, H. Barton Grossman, Colin Dinney, and Ashish Kamat Kelly BreeKelly Bree More articles by this author , Patrick HensleyPatrick Hensley More articles by this author , Nathan BrooksNathan Brooks More articles by this author , Lianchun XiaoLianchun Xiao More articles by this author , Yu ShenYu Shen More articles by this author , Neema NavaiNeema Navai More articles by this author , H. Barton GrossmanH. Barton Grossman More articles by this author , Colin DinneyColin Dinney More articles by this author , and Ashish KamatAshish Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002001.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current risk tables for outcome prediction in patients with non-muscle invasive bladder cancer (NMIBC) are based upon studies comprised primarily of low-grade tumors. We developed nomograms that predict disease recurrence and progression in patients with high-grade NMIBC using a large institutional dataset. METHODS: The log rank test, univariate and multivariate Cox proportional hazards regression models were used to identify risk factors of histologically confirmed disease recurrence and progression using data on 519 patients treated with adequate induction bacillus Calmette-Guerin (BCG) at our institution from 2000 to 2018. The first set of models predicted bladder cancer recurrence free survival (RFS), and the second set predicted tumor progression (any upstaging) free survival (PFS). RESULTS: At an estimated median follow-up time was 60.4 months (95% CI: 54-66.2), recurrence or death, whichever occurred first was recorded in 248 patients (47.8%) with a median RFS time of 73 months (95% CI, 52.6-91.2). Recurrent tumors (HR 1.78, 95% CI 1.33-2.33, p<0.0001), larger tumor size (HR 1.07, 95% CI 1.00-1.15, p=0.0487), and diabetes mellitus (HR 1.57, 95% CI 1.14-2.15, p=0.0055) were significantly associated with a higher risk of recurrence or death. Conversely, the receipt of maintenance BCG (mBCG) (HR 0.46, 95% CI 0.29-0.73, p=0.0008) and number of doses of mBCG (HR 0.92, 95% CI 0.89-0.94, p<0.0001) were associated with lower risk of events. Progression or death occurred in 128 patients (24.7%) with a median PFS time of 151 months (95% CI, 121.32-NA). Prior BCG (HR 2.19, 95% CI 1.23-3.88, p=0.0075) and older age (HR 1.041, 95% CI 1.02-1.06, p<0.001) were associated with higher risk of progression or death, while BMI≥25 (HR 0.519, 95% CI 0.35-0.78, p=0.0015) and number of doses of mBCG (HR 0.88, 95% CI 0.86-0.91, p<0.0001) were associated with lower risk of progression or death. These prognostic factors were integrated to construct nomograms for prediction of PFS and RFS. CONCLUSIONS: These nomograms provide personalized prediction of recurrence and progression in patients with high-grade NMIBC treated with BCG, and may help identify patients who may benefit most from early radical cystectomy. Source of Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research, the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant to AMK, and NIH/NCI UTMD Anderson SPORE in Genitourinary Cancer (Bladder) (P50CA091846) to CPND © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e298-e298 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kelly Bree More articles by this author Patrick Hensley More articles by this author Nathan Brooks More articles by this author Lianchun Xiao More articles by this author Yu Shen More articles by this author Neema Navai More articles by this author H. Barton Grossman More articles by this author Colin Dinney More articles by this author Ashish Kamat More articles by this author Expand All Advertisement Loading ...