INTRODUCTION:To better understand how treatment patterns, clinical outcomes, health-related quality of life, and healthcare resource utilization are impacted by initial prostate cancer diagnosis, prostate cancer family history, and race. PATIENTS:We conducted three subgroup analyses using the TRUMPET US registry of metastatic castration-resistant prostate cancer (mCRPC) patients: 1) initial diagnosis of non-metastatic hormone-sensitive prostate cancer (HSPC) versus de novo metastatic HSPC; 2) with prostate cancer family history versus none; 3) Caucasians versus African Americans. METHODS:Baseline characteristics, treatment patterns, health-related quality of life, and healthcare resource utilization were analyzed descriptively. Time-to-event outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards models, adjusted based on clinically important variables, including disease biology factors and selected variables showing large standardized mean differences between groups. RESULTS:This study included 832 patients with mCRPC. Patients with non-metastatic HSPC at initial diagnosis had a 32% lower risk of death than patients with de novo metastatic HSPC at initial diagnosis (adjusted HR: 0.68; 95% CI: 0.51, 0.91). Patients with prostate cancer family history had a significantly lower risk of death than patients with none (adjusted HR: 0.68; 95% CI: 0.51, 0.90). No statistically significant outcomes differences were identified between African American and Caucasian patients. Health-related quality of life changes were similar across all subgroups. CONCLUSION:Our analyses suggest that initial diagnosis and prostate cancer family history may meaningfully impact patients' survival and clinical outcomes. Future dedicated, prospective research should further elucidate how each of these factors affectclinical outcomes in the mCRPC context.

Background:Radical prostatectomy is a potentially curative treatment for localized prostate cancer (LPC), but there is limited literature comprehensively describing clinical and economic outcomes stratified by risk group. This study compared survival and healthcare costs following radical prostatectomy between patients with high-risk and low/intermediate-risk LPC in routine urology practice in the US. Methods:Linked electronic medical records and administrative claims were used to identify men with LPC undergoing radical prostatectomy (index date). Patients were classified into high-risk or low/intermediate-risk cohorts based on staging, prostate-specific antigen test results, and Gleason score, in alignment with the National Comprehensive Cancer Network®. Cohorts were balanced using inverse probability of treatment weighting. Metastasis-free survival and event-free survival post index were compared between cohorts using a weighted Cox proportional hazards model. All-cause/prostate cancer (PC)-related healthcare costs were compared post index using weighted ordinary least squares regression in a subgroup of patients with 12 months of continuous insurance eligibility prior to/including index. Results:Patients in the high-risk cohort (N=7542) had significantly higher rates of metastasis (36 months: hazard ratio [95% confidence interval (CI)]: 3.80 [3.31, 4.38], p<0.001; 60 months: 3.59 [3.19, 4.04], p<0.001) and disease progression (36 months: 3.49 [3.28, 3.71], p<0.001; 60 months: 3.37 [3.18, 3.57], p<0.001) compared to patients in the low/intermediate-risk cohort (N=11,429). In the cost subgroup, the high-risk cohort (N=1488) incurred significantly higher mean total all-cause healthcare costs (cost difference [95% CI]: $9134 [5999, 12,400] per-patient-per-year, p<0.001) and mean total PC-related healthcare costs ($7502 [4718, 10,279] per-patient-per-year, p<0.001) compared to the low/intermediate-risk cohort (N=2572) post index. Conclusion:In this real-world analysis of patients with LPC who underwent radical prostatectomy, high-risk disease was significantly associated with poorer survival and higher healthcare costs post-procedure compared to low/intermediate-risk LPC. These findings demonstrate the heightened clinical and economic burden observed with high-risk LPC.

# Background External beam radiation therapy (EBRT) and radical prostatectomy (RP) are definitive options for patients with localized or locally advanced prostate cancer (LPC). Limited evidence exists on the post-treatment economic burden in these patients. # Objective This real-world analysis investigated healthcare costs among Medicare beneficiaries with LPC who received EBRT or RP as initial definitive treatment. # Methods This is a retrospective, longitudinal cohort study using Surveillance, Epidemiology, and End Results (SEER)–Medicare database. Included were Medicare Fee-For-Service beneficiaries newly diagnosed with LPC at the age of ≥65 years during 2012-2019 and received either EBRT or RP as an initial definitive therapy. After the initial therapy, all-cause and prostate cancer–related costs were summarized and stratified by the earliest observed definitive therapy (RP vs EBRT) and the National Comprehensive Cancer Network risk classification (low/intermediate-risk [LIR-LPC] vs high-risk [HR-LPC]). # Results Of the 17 066 LPC patients treated with EBRT, 60% (N =10 321) had LIR-LPC and 40% (N = 6745) had HR-LPC. During the follow-up, the mean per-person-per-year all-cause cost was $9837 higher in the HR-LPC cohort than the LIR-LPC cohort ($34 441 vs $24 604; _P_ < .0001). Of the 9479 patients treated with RP, 43% (N = 4120) had LIR-LPC and 57% (N = 5359) had HR-LPC. The mean per-person-per-year all-cause cost during follow-up was $6829 higher in the HR-LPC cohort than the LIR-LPC cohort ($23 820 vs $16 991; _P_ < .0001). Across all cohorts, the largest all-cause healthcare cost category was outpatient, followed by inpatient and prescription drug. # Conclusions This real-world study on healthcare costs in patients with LPC treated with EBRT or RP showed HR-LPC is associated with significant incremental economic burden relative to LIR-LPC. The findings highlight the current unmet need for more cost-effective treatment strategies for HR-LPC.

Aim: This study examined the clinical outcomes of patients in the US with low/intermediate-risk localized prostate cancer (LIR-LPC) and high-risk localized prostate cancer (HR-LPC) who received radical prostatectomy (RP) as initial treatment. Materials & methods: This is a retrospective analysis of the SEERMedicare database. Patients newly diagnosed with LPC at age of ≥65 years during 2012–2019 who underwent RP as initial definitive treatment and had continuous Medicare Fee-For-Service for ≥12 months prior to RP were included. Eligible patients were stratified into LIR-LPC and HR-LPC cohorts. Overall survival, metastatic free survival and time to advanced prostate cancer treatment (TTAT) were described and compared using the Kaplan–Meier method and Cox proportional-hazards model. Results: The LIR-LPC cohort (n = 4120) and the HR-LPC cohort (n = 5359) had comparable socio-demographic characteristics, with a mean age of approximately 70 years. Survival analysis showed that HR-LPC was associated with significantly shorter overall survival, metastatic free survival and TTAT than LIR-LPC (log rank p < 0.001). After adjusting for comprehensive socio-demographic and baseline clinical characteristics, patients with HR-LPC had an approximately 70% increased risk for all-cause death (hazard ratio [HR]: 1.72; confidence interval [CI]:1.39–2.12), 2.5-fold increased risk formetastasis or death (HR: 2.57; CI: 2.14–3.09), and ninefold increased risk for initiating advanced treatments (HR: 9.06; CI: 6.22–13.18) compared with patients with LIR-LPC. Conclusion: In patients with LPC who received RP as initial definitive treatment, high risk is strongly associated with suboptimal clinical outcomes. Novel therapeutic approaches are needed to enhance the management and improve the outcomes for this patient population.

Introduction Racial disparities exist in the treatment of prostate cancer in the US, and robust data for African American (AA) vs Caucasian (CAU) patients with metastatic castration-resistant prostate cancer (mCRPC) are scarce. This study explored characteristics, treatment patterns, and outcomes of AA vs CAU patients with mCRPC in the real-world setting. Methods TRUMPET, a prospective, observational, multicenter study, enrolled 1028 patients who initiated CRPC treatment at 147 urology and oncology sites in the US (20152019). The post hoc analysis included patients with mCRPC who identified as AA or CAU. Patients were enrolled within 90 days of the decision to treat or treatment initiation. Characteristics and treatment patterns were analyzed descriptively; radiographic progression-free survival (rPFS), prostate-specific antigen PFS (PSA-PFS), overall survival (OS), and time to skeletal-related events (SREs) were analyzed using Kaplan–Meier methods and adjusted Cox proportional hazards models. An exploratory sub-analysis compared outcomes by race in patients initially treated with androgen receptor pathway inhibitors (ARPIs). Results In total, 133 AA vs 661 CAU patients with M1 CRPC at baseline were included: median age, 69.0 vs 74.0 years; hypertension, 72% vs 66%; diabetes, 32% vs 23%; osteoporosis, 5% vs 12%; other cancers, 6% vs 24%; PSA at diagnosis, 48.8 vs 13.9 ng/mL; N1 tumors, 17% vs 11%; M1 tumors, 29% vs 23%. Primary treatment before CRPC diagnosis (AA vs CAU patients): surveillance, 12% vs 19%; radical prostatectomy, 18% vs 36%; radiation, 48% vs 41%. Initial mCRPC treatment: chemotherapy, 12% vs 6%; ARPI, 62% vs 57%; immunotherapy, 29% vs 41%. After treatment initiation, a trend toward improved clinical outcomes was seen in AA vs CAU patients (Table). In the exploratory analysis, AA patients initiating ARPIs showed a trend toward improved OS vs CAU patients (adjusted median time to death [95% CI]: 41.86 [33.25, not estimable] vs 32.30 [28.62, 40.08] months; adjusted HR [95% CI]: 0.71 [0.45–1.14]). Conclusions AA patients were younger, had higher rates of some comorbidities and more severe disease, and were more likely to receive ARPIs or chemotherapy. Despite our initial hypothesis predicting differences favoring CAU patients, we observed generally similar treatment patterns and a trend toward better outcomes in AA patients. Further research is needed to better understand the outcomes of AA patients with mCRPC.

Supplementary Data for Antonarakis et al

Supplementary Fig 2. Analysis of survival by baseline median alkaline phosphatase across the two studies using the study-specific median.

PURPOSE:Prostate cancer (PCA) germline testing (GT) informs precision therapy, cancer screening, and hereditary cancer risk for patients and families. To support patient-centered PCA GT, studying patient-reported outcomes (PROs) is essential. METHODS:PROGRESS was a national patient-driven registry (January 2021-April 2022) for English-speaking males older than 18 years with previous/current PCA GT and Internet access. Surveys collected demographics, PCA history, family cancer history, mode of genetics care delivery, satisfaction with genetic counseling, decisional conflict, cancer genetics knowledge, and attitudes toward GT. Multiple linear regression modeling was used to estimate and draw inferences (α = .05) on strength of relationships between participant characteristics and PROs. RESULTS:Analyses focused on 414 participants: White (88%), Black (3%), Asian (6%), and mixed/other (3%). Most participants were non-Hispanic (95.2%) and 46.9% had PCA. Genetic results were positive (pathogenic/likely pathogenic variants; mutations) in 27.9%. The three most common modes of genetics care were meeting with genetics professional (in-person or remotely; 30.9%), discussing with doctor (21.1%), and using website (20.8%). In covariate-adjusted models, satisfaction scores were highest with pretest counseling by phone (β = 1.31; 95% CI, 0.26 to 2.36) or discussion with doctor (β = 1.25; 95% CI, 0.38 to 2.12). Lower decisional conflict scores were reported for pretest counseling by phone (β = -3.76; 95% CI, -7.28 to -0.24). Males with mutations reported higher GT benefit scores (β = .30; 95% CI, 0.02 to 0.59) and importance of GT (β = .34; 95% CI, 0.08 to 0.61). Asian Americans reported lower GT satisfaction (β = -2.91; 95% CI, -4.34 to -1.48) and higher decisional conflict (β = 8.93; 95% CI, 4.36 to 13.51). CONCLUSION:PROGRESS Registry informs the first comprehensive report of PROs among males undergoing PCA GT, providing insights into opportunities to improve patient experience and leverage the benefit of GT.

Introduction Patients with bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) are at significant risk for recurrence and progression. Although cystectomy is a recommended definitive treatment, it is associated with morbidity and mortality. Nadofaragene firadenovec-vncg is a nonreplicating recombinant adenovirus vector-based gene therapy that delivers human interferon alpha-2b cDNA into the bladder epithelium. In a phase 3 study (NCT02773849), 55/103 participants (53.4%) with carcinoma in situ (CIS) with or without papillary tumors (± Ta/T1) achieved a complete response (CR) by 3 months. Here, cystectomy-free survival (CFS) and pathologic outcomes at cystectomy were evaluated among participants with BCG-unresponsive NMIBC with CIS ± Ta/T1 treated with nadofaragene firadenovec, stratified by CR status at 3 months. The objective of this analysis was to test the hypothesis that nadofaragene firadenovec would enable many participants to avoid cystectomy without compromising the window of cure for those who did not achieve or maintain a CR. Methods An open-label, multicenter, phase 3 study enrolled participants with BCG-unresponsive NMIBC to receive a single dose of nadofaragene firadenovec, with repeat dosing every 3 months in the absence of high-grade recurrence. Incidence of cystectomy and CFS (calculated from the first dose of nadofaragene firadenovec to the first date of cystectomy or death due to any cause) were assessed through 5 years of follow-up. Cystectomy pathology reports were assessed through the 36-month data cutoff (the 36-month visit of the last enrolled participant) to evaluate stage and progression. Results are presented for the overall CIS ± Ta/T1 population and stratified by CR status at 3 months. Results Median follow-up time was 48.9 months among all treated participants with CIS ± Ta/T1 (N=107). Among participants included in efficacy analyses (N=103), 44 (42.7%) underwent cystectomy, including 15 (14.6%) who achieved a CR at 3 months and 29 (28.2%) who did not. Of the 37 participants who underwent cystectomy with pathology data available, 6 had MIBC at cystectomy, of whom 3 had MIBC at transurethral resection before cystectomy and 3 underwent cystectomy for clinical NMIBC. Three participants were pT0 at cystectomy. The Kaplan–Meier (KM) estimated median duration of CFS was 47.9 months, 63.9 months, and 11.3 months in all participants with CIS ± Ta/T1, participants with a CR, and participants without a CR, respectively (Table). The KM probability of CFS for at least 60 months was 43.2%, 65.5%, and 16.0% in all participants with CIS ± Ta/T1, participants with a CR, and participants without a CR, respectively. Conclusions Nadofaragene firadenovec treatment resulted in clinically meaningful CFS for participants with BCG-unresponsive NMIBC with CIS ± Ta/T1, particularly among those who achieved an initial CR at 3 months. The rate of upstaging at the time of cystectomy was consistent with historical reports on immediate cystectomy for NMIBC, indicating nadofaragene firadenovec is a safe bladder-sparing option that does not sacrifice the window of cure for patients with BCG-unresponsive NMIBC.

Background Bladder EpiCheck (BE) is a novel methylation-based PCR urine test for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences. Objective We present the results of a North American study evaluating BE and meta-analysis of literature. Methods A prospective, blinded, multicenter study was conducted in North America. Voided urine was collected from NMIBC patients prior to cystoscopic surveillance. BE testing was performed centrally. For the meta-analysis, a PUBMED search was performed to identify all published peer-reviewed clinical studies of BE for NMIBC surveillance. Results In this study, 674 patients were enrolled of which 449 were included. Overall sensitivity was 67% (95%CI 58%-74%), specificity was 84% (80%-88%), PPV was 65% (57%-73%) and NPV was 85% (81%-89%). For high-grade (HG) recurrence, sensitivity was 77% (65%-85%) and NPV was 95% (92%-97%). In patients with negative cystoscopy and cytology at the first study visit, risk of subsequent recurrence in 12 months was 5.3 (2.7–10.3) times higher in patients with positive BE vs. negative BE (p < 0.0001). In patients with negative cystoscopy and equivocal cytology, BE was positive in 75–89% of those with later HG recurrence, with PPV of 42% (15%-72%)-63% (38%-84%). The meta-analysis included 7 studies and 1564 patients. Overall sensitivity was 82% (66–92%), HG sensitivity was 91% (82–95%), specificity was 85% (80–88%), PPV was 60% (55–64%) and HG NPV was 98% (97–99%). Conclusions The consistently strong performance of BE indicate that a positive test could improve timely disease recurrence detection and a negative test could rule-out HG disease. Furthermore, the low rate of false positive results, potentially minimizes unnecessary downstream procedures and patient anxiety.

Supplementary Fig 3 In vivo cellular and humoral responses through 52 weeks are illustrated here.

Supplementary Fig 1 Analysis of Survival by Baseline Median PSA across the two studies using the study-specific median and quartiles.

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-01 EFFICACY OF NADOFARAGENE FIRADENOVEC-VNCG FOR PATIENTS WITH BACILLUS CALMETTE-GUÉRIN-UNRESPONSIVE NON-MUSCLE-INVASIVE BLADDER CANCER: FINAL RESULTS FROM A PHASE 3 TRIAL Stephen A. Boorjian, Vikram M. Narayan, Badrinath R. Konety, Viraj A. Master, Neal D. Shore, Ashish M. Kamat, Trinity J. Bivalacqua, Max R. Kates, Jeffrey S. Montgomery, Seth P. Lerner, Paul L. Crispen, Gary D. Steinberg, Piyush K. Agarwal, Anne K. Schuckman, Robert S. Svatek, Brian R. Lane, Lawrence I. Karsh, Marc A. Bjurlin, Gordon A. Brown, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Eric H. Kim, Alexander I. Sankin, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, and Colin P. N. Dinney Stephen A. BoorjianStephen A. Boorjian , Vikram M. NarayanVikram M. Narayan , Badrinath R. KonetyBadrinath R. Konety , Viraj A. MasterViraj A. Master , Neal D. ShoreNeal D. Shore , Ashish M. KamatAshish M. Kamat , Trinity J. BivalacquaTrinity J. Bivalacqua , Max R. KatesMax R. Kates , Jeffrey S. MontgomeryJeffrey S. Montgomery , Seth P. LernerSeth P. Lerner , Paul L. CrispenPaul L. Crispen , Gary D. SteinbergGary D. Steinberg , Piyush K. AgarwalPiyush K. Agarwal , Anne K. SchuckmanAnne K. Schuckman , Robert S. SvatekRobert S. Svatek , Brian R. LaneBrian R. Lane , Lawrence I. KarshLawrence I. Karsh , Marc A. BjurlinMarc A. Bjurlin , Gordon A. BrownGordon A. Brown , Yair LotanYair Lotan , Brant A. InmanBrant A. Inman , Michael B. WilliamsMichael B. Williams , Michael S. CooksonMichael S. Cookson , Sam S. ChangSam S. Chang , Eric H. KimEric H. Kim , Alexander I. SankinAlexander I. Sankin , Dorte RehmDorte Rehm , Jørn S. JakobsenJørn S. Jakobsen , Kristian JuulKristian Juul , and Colin P. N. DinneyColin P. N. Dinney View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prospective clinical trials to evaluate long-term durability of bladder-preserving therapies for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) are limited. Nadofaragene firadenovec-vncg (ADSTILADRIN®) is a novel replication-deficient recombinant adenovirus vector-based gene therapy for high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (± Ta/T1). The phase 3 trial met its primary endpoint as 53.4% (95% confidence interval [CI]: 43.3, 63.3) of patients achieved a complete response by 3 months. Final outcomes from the 60-month follow-up are reported. METHODS: This open-label, multicenter phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive NMIBC in 2 cohorts: CIS±Ta/T1 (CIS; n=107) and Ta/T1 without CIS (papillary disease [PD]; n=50). Patients received nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology efficacy assessments. Mandatory biopsies were taken at 12 months, after which patients entered a 4-year follow-up and those remaining high-grade recurrence free (HGRF) were offered continued treatment at the investigator's discretion. RESULTS: For all treated patients, median follow-up was 50.8 months (interquartile range: 39.1, 60.0) with 26.8% of patients receiving 5 or more instillations and 7.6% of patients receiving treatment for at least 57 months. In the efficacy analysis set, 5.8% of patients with CIS and 14.6% of patients with PD were HGRF at month 57. Kaplan-Meier (KM)-estimated HGRF survival rate at 57 months was 13.2% (95% CI: 6.9, 21.5) and 32.7% (19.5, 46.6) in the CIS and PD cohorts, respectively. Within 5 years after the first dose of nadofaragene firadenovec, 40.8% and 29.2% of patients in the CIS and PD cohorts underwent radical cystectomy, respectively. KM-estimated overall survival at 60 months was 76.3% (64.6, 84.5) and 85.9% (70.9, 93.5) in the CIS and PD cohorts, respectively. Four patients with CIS and 1 patient with PD experienced progression to muscle-invasive disease documented by transurethral resection of bladder tumor at the time of high-grade recurrence as collected in the electronic case report form. No new safety signals were identified on long-term follow-up. CONCLUSIONS: Nadofaragene firadenovec provided nearly half of participants with bladder preservation at 60 months and represents a safe intravesical treatment option for patients with BCG-unresponsive CIS±Ta/T1 and Ta/T1 without CIS. Source of Funding: The ongoing follow-up of the phase 3 study is sponsored by Ferring Pharmaceuticals Ltd. The original study was funded by FKD Therapies Oy © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e987 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stephen A. Boorjian More articles by this author Vikram M. Narayan More articles by this author Badrinath R. Konety More articles by this author Viraj A. Master More articles by this author Neal D. Shore More articles by this author Ashish M. Kamat More articles by this author Trinity J. Bivalacqua More articles by this author Max R. Kates More articles by this author Jeffrey S. Montgomery More articles by this author Seth P. Lerner More articles by this author Paul L. Crispen More articles by this author Gary D. Steinberg More articles by this author Piyush K. Agarwal More articles by this author Anne K. Schuckman More articles by this author Robert S. Svatek More articles by this author Brian R. Lane More articles by this author Lawrence I. Karsh More articles by this author Marc A. Bjurlin More articles by this author Gordon A. Brown More articles by this author Yair Lotan More articles by this author Brant A. Inman More articles by this author Michael B. Williams More articles by this author Michael S. Cookson More articles by this author Sam S. Chang More articles by this author Eric H. Kim More articles by this author Alexander I. Sankin More articles by this author Dorte Rehm More articles by this author Jørn S. Jakobsen More articles by this author Kristian Juul More articles by this author Colin P. N. Dinney More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND/OBJECTIVES:Unfortunately, not all metastatic castration resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing in prostate cancer. SUBJECTS/METHODS:In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science. RESULTS/CONCLUSION:We argue for the widespread adoption of germline testing in all patients with prostate cancer and for somatic mutations testing in patients at the time of recurrent/metastatic disease. In this first part, we review how genomic testing is performed. We also review how to overcome certain barriers to integrate genetic and biomarker testing into clinical practice.

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-07 PIVOTAL STUDY EVALUATING PERFORMANCE OF BLADDER EPICHECK, AN FDA CLEARED TEST, IN NON-MUSCLE INVASIVE BLADDER CANCER Brant Inman, H. Barton Grossman, Neil Fleshner, Jonathan Wright, Kelvin Moses, Ryan Berglund, Jason Hafron, Lawrence Karsh, Daniel Saltzstein, and Yair Lotan Brant InmanBrant Inman , H. Barton GrossmanH. Barton Grossman , Neil FleshnerNeil Fleshner , Jonathan WrightJonathan Wright , Kelvin MosesKelvin Moses , Ryan BerglundRyan Berglund , Jason HafronJason Hafron , Lawrence KarshLawrence Karsh , Daniel SaltzsteinDaniel Saltzstein , and Yair LotanYair Lotan View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer is the 5th most common cancer in the US. NMIBC surveillance with cystoscopy and cytology is invasive and operator dependent. Bladder EpiCheck (BE) is an accurate non-invasive & objective novel methylation-based PCR urine test included in the EAU guidelines that could potentially augment NMIBC surveillance. These are the results of the FDA pivotal study for BE's 510K clearance. METHODS: A prospective, blinded, multicenter, 3-visit study in 11 centers in USA and Canada. NCT02700464 Adult bladder cancer patients within 12 months of TURBT and under cystoscopic surveillance, were eligible. Patients planned for cystectomy or chemoradiation were excluded. The gold standard (GS) positive was either positive cystoscopy confirmed by pathology or positive cytology (HGUC and SHGUC). All others were considered GS negative. Voided urine was collected prior to cystoscopy. The first GS positive visit was used for analysis and if all visits were negative, the last negative visit was used for analysis. Wash urine samples were excluded. BE detects methylation patterns of 15 loci in urine cell DNA associated with urothelial carcinoma. BE testing was performed on ABI® 7500 Fast Dx PCR (Thermo Fisher) at two central CLIA-certified laboratories in the US. RESULTS: 674 subjects were enrolled and 449 were included in analysis (Figure 1). Median age was 71 (38-93), 79% were male, 47% had history of ≥1 recurrence and 51% were treated with instillations since last TURBT. Overall sensitivity, specificity, NPV and PPV were 67%, 84%, 85%, 65%, respectively. HG sensitivity and NPV were 77% and 95% (Table 1). Performance was statistically different by grade, but not impacted by any other factor including, sex, smoking history, occupational risk, time from last instillation treatment. In patients with a negative GS, the rate of subsequent recurrence at one of the two first study visits was 53% compared to 10% of subjects with positive and negative BE, respectively. CONCLUSIONS: BE performance could improve timely disease recurrence detection and compliance with NMIBC surveillance. BE's high HG NPV supports the use as a rule-out test for HG disease. With high specificity and PPV, BE's false positive rates are low, potentially minimizing unnecessary downstream procedures and patient anxiety. Download PPT Source of Funding: Nucleix Ltd © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e990 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Brant Inman More articles by this author H. Barton Grossman More articles by this author Neil Fleshner More articles by this author Jonathan Wright More articles by this author Kelvin Moses More articles by this author Ryan Berglund More articles by this author Jason Hafron More articles by this author Lawrence Karsh More articles by this author Daniel Saltzstein More articles by this author Yair Lotan More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction Patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) are at significant risk for recurrence and progression and there is an unmet need for local, effective, bladder-preserving treatment options. Nadofaragene firadenovec, a non-replicating recombinant adenovirus vector-based gene therapy that delivers a copy of the human interferon alfa-2b gene into the bladder epithelium, is approved by the FDA for treatment of adult patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (±Ta/T1). The Phase 3 study of nadofaragene firadenovec met its primary endpoint;;53.4% of patients with CIS±Ta/T1 achieved;complete response (CR) at three months. The 24-month follow-up results showed that nadofaragene firadenovec was well tolerated, and 36.4% of the patients with CIS±Ta/T1 who achieved a CR remained high-grade recurrence free (HGRF) at 24 months. Herein, we report 36-month follow-up results from the Phase 3 study for the CIS±Ta/T1 cohort. Methods The open-label Phase 3 study enrolled 107 patients with BCG-unresponsive NMIBC with CIS±Ta/T1 (NCT02773849). The efficacy analysis for this cohort included 103 patients who met the protocol definition of BCG-unresponsive NMIBC. Patients received 75 mL of nadofaragene firadenovec (3×1011 viral particles/mL) once every 3 months for up to 4 doses. The protocol mandated a 5-site biopsy (dome, trigone, right and left lateral walls, posterior wall) at 12 months and patients who were HGRF were offered continued treatment once every 3 months at the investigator's discretion. Assessments beyond 24 months were performed in accordance with usual clinical practice. The study is ongoing, with a planned 5-year treatment and monitoring phase; the follow-up results reported here are based on the 36-month interim data for the CIS±Ta/T1 cohort. Results Mean (standard deviation) duration of follow-up for the entire cohort was 42.1 (12.6) months*, with a total of 13/107 (12.1%) patients having received 36 months of treatment.At 36 months, 14/55 (25.5%) patients who had achieved a CR at 3 months remained HGRF. For these patients, the Kaplan–Meier (KM)-estimated probability of duration of CR for at least 12, 24 and 36 months was 46.5%, 36.6% and 34.2%, respectively (Figure).In the overall CIS±Ta/T1 cohort (N=103), the KM-estimated median (95% confidence interval [CI]) duration of HGRF survival was 6.0 (3.4, 8.3) months, and probability;(95% CI) of HGRF survival for at least 12 months was 30.1% (21.5, 39.2). Two patients (1.9%) discontinued due to adverse events, while four (3.9%) experienced progression to muscle-invasive disease. The KM-estimated cystectomy-free survival (95% CI) at 36 months was 53.8% (43.3, 63.1), and the three-year overall survival was 90.4% (82.3, 94.9). Conclusions Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio.*All patients had passed 36 months at data cutoff on 09 September 2021.Figure. Kaplan–Meier estimated durability of complete response in patients with CIS±Ta/T1 papillary disease.