BACKGROUND AND OBJECTIVE:Patients with high-risk non-muscle invasive bladder cancer (NMIBC) experience high recurrence rates and potential understaging, supporting guideline recommendations for repeat transurethral resection (reTUR). However, identifying patients best suited for reTUR remains challenging. Here, we analyze urine tumor DNA (utDNA) for mutations associated with urothelial cancer in a cohort of patients undergoing reTUR. METHODS:Retrospective evaluation of urine samples from 43 patients with pathologically confirmed high-grade NMIBC who were undergoing reTUR. Urine was collected immediately prior to reTUR and evaluated using UroAmp. The primary objective of this study was to compare utDNA disease classification with pathological staging from reTUR. Prognostic (high/low-risk) and minimal residual disease (MRD) (positive/negative) classifications were evaluated. KEY FINDINGS AND LIMITATIONS:The stage distribution from reTUR was 32% T0 (no residual disease), 29% Ta ±CIS, 28% T1 ±CIS, and 11% T2. Prognostic risk classification had 97% sensitivity (95% confidence interval [CI] 86-100) and 89% negative predictive value (95% CI 59-99). MRD classification had 80% specificity (95% CI 56-94) and 88% positive predictive value (95% CI 72-97). When long-term recurrence outcomes were considered, positive predictive value increased to 92% (95% CI 78-98) for both classification algorithms. Among T0 samples, utDNA high-risk patients had recurrence-free survival of 36%, compared to 100% for utDNA low-risk patients (p = 0.006). CONCLUSIONS AND CLINICAL IMPLICATIONS:utDNA testing identifies residual disease prior to reTUR. utDNA can serve as an adjunct following initial transurethral resection, aiding in the assessment of resection completeness, determining the need and timing of repeat resection, and stratifying risk of future recurrence.

BACKGROUND. Current diagnosis and surveillance of bladder cancer rely on cystoscopy, which is invasive and user dependent. The urine mRNA panel, uRNAp, measures expression of 3 genes for identification of bladder cancer. Here we report validation of uRNAp for patients undergoing initial workup for suspected bladder cancer and surveillance for bladder cancer. METHODS. Urine specimens were prospectively collected prior to cystoscopy at 2 health care systems from patients without (detection cohort) or with (surveillance cohort) a history of bladder cancer. RNA was isolated from urine sediment for RT-qPCR to determine roundabout guidance receptor 1, corticotropin releasing hormone, and insulin-like growth factor 2 expression and calculate the uRNAp bladder cancer probability score. RESULTS. In the detection cohort, 547 samples were collected from 529 patients. There were 123 new diagnoses of bladder cancer in the detection cohort, and uRNAp demonstrated 98% sensitivity and 51% specificity for identification of bladder cancer. In the surveillance cohort, 1,543 samples were collected from 447 patients with 286 recurrences. uRNAp demonstrated 94% overall sensitivity with 43% specificity and 99% sensitivity for high-grade recurrence. The receiver operating characteristic area under the curve was 0.92 in the detection and 0.81 in the surveillance cohort. uRNAp scores significantly increased with tumor size and grade. CONCLUSION. Prospective validation of uRNAp demonstrated a strong potential clinical utility as a noninvasive adjunct to cystoscopy for management of bladder cancer. uRNAp may be a useful triage tool to defer or expedite cystoscopy for patients undergoing detection or surveillance of bladder cancer. FUNDING. Department of Veterans Affairs BLR&D Merit Review I01 BX004962 to JCL.

Only some non-muscle-invasive bladder cancer (NMIBC) patients benefit from intravesical Bacillus Calmette-Guérin (BCG), and predictive biomarkers remain lacking. While urine tumor DNA (utDNA) analysis is promising, mutations in tumor-adjacent normal urothelium, namely the field effect, limit specificity. Here, we show that the prevalence of somatic mutations in the urine increases with age. We introduce an improved utDNA minimal residual disease (MRD) approach that increases specificity by removing field-effect mutations. Applying this field-effect-informed MRD approach to 261 samples from NMIBC patients undergoing surgery and adjuvant BCG, we identify three molecular response classes, including surgical responders, BCG responders, and non-responders. Molecular predictors of response to the two treatments differ, with pre-existing immune activation and higher mutation burden enriched in BCG but not surgery responders. These findings highlight the potential of field-effect-informed liquid biopsy methods for guiding personalized therapy and uncovering biomarkers for individual components of multimodal treatments.

OBJECTIVE:To improve access to the general urology clinics for urgent urology referrals. The issue of healthcare accessibility is relevant to urology, since certain urologic conditions require urgent assessment. Despite guidelines for timely assessment, challenges in clinic scheduling frequently cause patient care delays. METHODS:The prospective quality improvement study was conducted at outpatient general urology clinics from June 2023 to May 2024. An A3 quality improvement framework was used to develop, implement, and iterate on interventions intended to reduce wait times for urgent urology referrals. These included defining truly urgent diagnoses, streamlining referral template, allocating and protecting urgent clinic slots, and enhancing communication with multidisciplinary stakeholders. RESULTS:A total of 1058 urgent urology patients in the ambulatory setting were seen during the project timeframe. At baseline, mean wait time for urgent referrals was 59.0days, and 3 patients per week were seen within 10days of referral. Following implementation of interventions, the mean wait time decreased to 21.6 days, and 8 patients per week were seen within 10 days (P < .01). These processes were not associated with an adverse effect on wait times for routine referrals during the study. CONCLUSION:Barriers to timely clinic access for urgent referrals include undefined definitions of urgency, lack of resource allocation dedicated for urgent patients, and lack of communication between referring providers, patient coordinators, and clinic staff. A streamlined referral process that addresses these issues can lead to significant and sustainable reduction in care delay for urgent urology patients.

INTRODUCTION:Consistent urologic oncology follow-up after radical cystectomy (RC) improves survival. However, there is scarce literature describing postoperative communication. We aimed to identify differences in postoperative communication patterns and healthcare utilization among English-speaking patients (ESPs) and patients with limited English proficiency (LEP) following RC. METHODS:We conducted a single-institution, retrospective cohort study, examining patients who underwent RC for bladder cancer. We used propensity score matching to match 50 ESPs and 50 patients with LEP on age and sex. We abstracted patient demographics, postoperative communication and healthcare utilization within 90 days of surgery. We fit multivariable linear regression to investigate factors associated with postoperative communication frequency. RESULTS:Postoperative communication was common, with 82% of patients placing ≥1 phone call/message. ESPs communicated more than patients with LEP (6.04 vs. 3.80 average calls/messages), though this difference was not statistically significant (P = 0.08). ESPs were more likely to initiate the communication themselves and have postoperative communication result in reassurance from the surgical team (P = 0.03), while patients with LEP were more likely to have a family member communicate on their behalf (P < 0.001) and have postoperative communication result in outpatient evaluation/treatment (P = 0.01). Patients with a neobladder reconstruction placed an increased number of phone calls/messages. There were no differences in postoperative healthcare utilization between the 2 groups. CONCLUSIONS:Postoperative communication is frequent following RC. ESPs communicated nearly twice as often as patients with LEP, suggesting a clinically relevant difference in patient communication following radical cystectomy. Primary language spoken is not associated with differences in postoperative healthcare utilization.

Myofascial pain syndrome (MPS) is a common musculoskeletal pain disorder with increased prevalence in individuals with comorbidities including cancer, stroke, osteoarthritis, mental health conditions, and more. Despite its prevalence, there is a lack of clinically feasible, evidence-based outcome measures for MPS diagnosis. The windup phenomenon is a frequency-dependent increase in neuronal excitability to input stimuli, facilitating temporal summation of pain that's commonly associated with central sensitization. Emerging evidence strongly links myofascial pain pathophysiology to central sensitization. This study aims to investigate the physiologic expression of the windup phenomenon in different MPS clinical phenotypes to assess its clinical feasibility as a psychophysical diagnostic outcome measure. A cross-sectional analysis categorized myofascial pain patients into three groups: active (n=12) with spontaneous pain, latent (n=6) with pain upon palpation but not spontaneously, and pain-free controls (n=6). An experienced physiatrist or physical therapist determined group classification. The windup phenomenon was bilaterally tested over the trapezius muscle using a 16-pinprick stimulus at 1 Hz with a 256 mN weighted pinprick (MRC Systems, Heidelberg, Germany). The Sumsquare outcome measure (Clouse, 2021) quantified windup magnitude. Significant increases in Sumsquare were observed in the active group compared with latent (374, 95%CI [36.6,711], p=0.0287) and controls (377, 95%CI [47.9,707], p=0.0242). No Sumsquare difference was observed between latent and normal groups (3.54, 95%CI [-122,130], p=0.9997). Symptomatic myofascial pain patients exhibit enhanced windup compared to asymptomatic latent and control groups, suggesting windup's clinical feasibility as a psychophysical outcome measure in myofascial pain phenotyping. Larger studies are needed for further validation.

577 Background: Trimodality bladder preservation is an acceptable alternative to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). Multiple retrospective studies have reported similar disease control rates and overall survival rates with chemoradiation (CRT), but the benefit of neoadjuvant chemotherapy (NAC) prior to CRT is not established. This study investigates the outcomes of CRT with or without NAC for management of MIBC. Methods: Retrospective analysis of 135 adult patients with muscle invasive bladder cancer evaluated in the Department of Radiation Oncology over 7 years (2016-2022). Patients were excluded if they did not receive NAC or if they underwent RC. Patients were treated with NAC followed by CRT. Overall survival (OS), progression-free survival (PFS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier methods. Follow-up was censored at 36 months after treatment. Differences in survival outcomes by completion of status of NAC were analyzed using log-rank tests. All survival analyses were performed in SAS version 9.4. Results: Of the 135 evaluated patients, 38 were treated with NAC followed by CRT. The 24-month OS, PFS, and MFS were 76% [95% CI 62-92%], 60% [95% CI 46-79%], and 72% [95% CI 58-90%] respectively. The 24-month PFS in patients who received a full course of NAC was 66.0% [95% CI 50-87%]) and 38.0% [95 CI 15-92%] in those who did not complete NAC regimen. Overall PFS was significantly higher in the NAC cohort (log-rank p=0.03). There was no significant difference in OS between patients who completed prescribed course of NAC versus those who did not (log-rank p=0.48). Treatment was overall well tolerated with 28.2% of grade 2 or higher RT toxicity. Conclusions: NAC prior to CRT achieved excellent short term disease-free and survival outcomes in patients with non-metastatic MIBC. This analysis is limited by its retrospective nature but suggests that completion of NAC prior to CRT may be associated with lower rates of disease recurrence. [Table: see text]

You have accessJournal of UrologySurgical Technology & Simulation: Artificial Intelligence II (PD27)1 May 2024PD27-12 DEVELOPMENT AND VALIDATION OF GENERALIZABLE INTERPRETABLE AI BIOMARKERS TO PREDICT CLINICAL OUTCOMES IN BCG-TREATED PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER Yair Lotan, Jay B. Shah, Viswesh Krishna, Bryn Launer, Vrishab Krishna, Siddhant Shingi, Jennifer Gordetsky, Thomas Gerald, Eugene Shkolyar, Dickon Hayne, Andrew Redfern, Lisa Spalding, Courtney Stewart, Vikram Narayanan, Dattatreya Patil, Vignesh T. Packiam, Anand Rajan, Michael A. O'Donnell, Loic Baekelandt, Mario I. Fernandez, Marcela Schultz, Patrick J. Hensley, Derek B. Allison, John A. Taylor, Ameer Hamza, Vivek Nimgaonkar, Ekin Tiu, Louis J. Vaickus, Snehal Sonawane, Daniel L. Miller, Damir Vrabac, Waleed M. Abuzeid, Anirudh Joshi, Sam S. Chang, and Stephen B. Williams Yair LotanYair Lotan , Jay B. ShahJay B. Shah , Viswesh KrishnaViswesh Krishna , Bryn LaunerBryn Launer , Vrishab KrishnaVrishab Krishna , Siddhant ShingiSiddhant Shingi , Jennifer GordetskyJennifer Gordetsky , Thomas GeraldThomas Gerald , Eugene ShkolyarEugene Shkolyar , Dickon HayneDickon Hayne , Andrew RedfernAndrew Redfern , Lisa SpaldingLisa Spalding , Courtney StewartCourtney Stewart , Vikram NarayananVikram Narayanan , Dattatreya PatilDattatreya Patil , Vignesh T. PackiamVignesh T. Packiam , Anand RajanAnand Rajan , Michael A. O'DonnellMichael A. O'Donnell , Loic BaekelandtLoic Baekelandt , Mario I. FernandezMario I. Fernandez , Marcela SchultzMarcela Schultz , Patrick J. HensleyPatrick J. Hensley , Derek B. AllisonDerek B. Allison , John A. TaylorJohn A. Taylor , Ameer HamzaAmeer Hamza , Vivek NimgaonkarVivek Nimgaonkar , Ekin TiuEkin Tiu , Louis J. VaickusLouis J. Vaickus , Snehal SonawaneSnehal Sonawane , Daniel L. MillerDaniel L. Miller , Damir VrabacDamir Vrabac , Waleed M. AbuzeidWaleed M. Abuzeid , Anirudh JoshiAnirudh Joshi , Sam S. ChangSam S. Chang , and Stephen B. WilliamsStephen B. Williams View All Author Informationhttps://doi.org/10.1097/01.JU.0001008580.58088.27.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Few markers exist that predict recurrence or progression in high-risk non-muscle invasive bladder cancer (HR NMIBC). We developed a deep learning pipeline that extracts generalizable interpretable features from digitized pathology slides. We validated histologic assays that predict recurrence, progression and BCG response in a multicenter cohort. METHODS: Digital H&E pathology slides and longitudinal clinical data were collected. Existing pretreatment diagnostic slides were converted to whole slide images and were not recut or re-stained to optimize model generalizability. Cell and tissue segmentation and classification models were developed from >1.5 million data points annotated by pathologists. Digital features associated with high-grade recurrence free survival (RFS), progression free survival (PFS) and BCG response were identified in the development (dev) set and then feature-locked biomarker assays were tested on an independent validation (val) set. Patients were classified into high (AI-H) and low (AI-L) risk of recurrence and progression and for presence/absence of a BCG Unresponsive Biomarker (BUB). RESULTS: Cell and tissue models had 0.99 AUC on the test set. AI models generalized across centers & slide preparation (Figure 1) and were robust to scanner model & magnification (r=0.99). 1071 HR NMIBC patients (dev: 311, val: 760) from 12 centers (med followup: 34 mo) were included. Features related to tumor aggressiveness, nuclear atypia, and immune response were associated with clinical outcomes. On regression analysis, AI groups predicted outcomes independent of age, sex, smoking status, grade, stage, presence of CIS and multifocality. In the val set, AI-H cases had significantly inferior RFS and PFS vs AI-L cases (HR 2.32, 3.08, p<0.001) with higher recurrence risk (1.9x & 1.7x at 1 & 2 yrs) and progression risk (2.9x & 2.5x at 1 & 5 yrs). BCG unresponsive status was 1.8x higher in BUB+ vs BUB- cases. CONCLUSIONS: We developed and validated AI assays that are robust to real-world variations across centers, preparation and digital scanning methods. These assays can be used to identify HR NMIBC cases with significantly higher risk of recurrence, progression, and BCG unresponsive status who may benefit from alternative therapies. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e555 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yair Lotan More articles by this author Jay B. Shah More articles by this author Viswesh Krishna More articles by this author Bryn Launer More articles by this author Vrishab Krishna More articles by this author Siddhant Shingi More articles by this author Jennifer Gordetsky More articles by this author Thomas Gerald More articles by this author Eugene Shkolyar More articles by this author Dickon Hayne More articles by this author Andrew Redfern More articles by this author Lisa Spalding More articles by this author Courtney Stewart More articles by this author Vikram Narayanan More articles by this author Dattatreya Patil More articles by this author Vignesh T. Packiam More articles by this author Anand Rajan More articles by this author Michael A. O'Donnell More articles by this author Loic Baekelandt More articles by this author Mario I. Fernandez More articles by this author Marcela Schultz More articles by this author Patrick J. Hensley More articles by this author Derek B. Allison More articles by this author John A. Taylor More articles by this author Ameer Hamza More articles by this author Vivek Nimgaonkar More articles by this author Ekin Tiu More articles by this author Louis J. Vaickus More articles by this author Snehal Sonawane More articles by this author Daniel L. Miller More articles by this author Damir Vrabac More articles by this author Waleed M. Abuzeid More articles by this author Anirudh Joshi More articles by this author Sam S. Chang More articles by this author Stephen B. Williams More articles by this author Expand All Advertisement PDF downloadLoading ...

Objectives: Perioperative blood transfusion (PBT) has been associated with worse survival after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Here, we evaluated the association between PBT and survival after RC that was preceded by neoadjuvant chemotherapy (NAC). Methods: A retrospective analysis was performed on 949 patients with cT2-4aN0M0 bladder cancer who received NAC prior to RC between 2000 and 2013 at 19 centers. Kaplan–Meier estimates of overall survival (OS) were made. Presumed risk factors for OS were analyzed using Cox regression analysis. PBT was defined by the administration of any packed red blood cells during surgery or during the post-operative hospital stay. Results: A transfusion was given to 608 patients (64%). Transfused patients were more likely to have adverse clinical and pathologic parameters, including clinical stage and performance status. Transfused patients had worse OS (p = 0.01). On multivariable Cox regression, PBT was found to be independently associated with worse OS (HR 1.53 (95% CI 1.13–2.08), p = 0.007). Conclusions: PBT is common after NAC and RC, which may be linked, in part, to the anemia induced by NAC. PBT was associated with several adverse risk factors that correlate with poor outcomes after NAC and RC, and it was an independent predictor of adverse OS on multivariable analysis. Further study should determine if measures to avoid blood loss can reduce the need for PBT and thereby improve patient outcomes.

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP71)1 May 2024MP71-19 ULTRASENSITIVE URINARY LIQUID BIOPSY ANALYSIS FOR BCG RESPONSE ASSESSMENT IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER William Y. Shi, Kevin J. Liu, Mohammad S. Esfahani, Joseph G. Schroers-Martin, Monica Nesselbush, Simon B. Chen, Stefan K. Alig, Patrick Mullane, Kathleen E. Mach, Ludimila Trabanino, Timothy J. Lee, Ihna Yoo, Vinh La, Gabriela Rodriguez, Zachary Kornberg, Eugene Shkolyar, Harcharan Gill, Alan Thong, Jay B. Shah, Kris Prado, Eila C. Skinner, Ash A. Alizadeh, Joseph C. Liao, and Maximilian Diehn William Y. ShiWilliam Y. Shi , Kevin J. LiuKevin J. Liu , Mohammad S. EsfahaniMohammad S. Esfahani , Joseph G. Schroers-MartinJoseph G. Schroers-Martin , Monica NesselbushMonica Nesselbush , Simon B. ChenSimon B. Chen , Stefan K. AligStefan K. Alig , Patrick MullanePatrick Mullane , Kathleen E. MachKathleen E. Mach , Ludimila TrabaninoLudimila Trabanino , Timothy J. LeeTimothy J. Lee , Ihna YooIhna Yoo , Vinh LaVinh La , Gabriela RodriguezGabriela Rodriguez , Zachary KornbergZachary Kornberg , Eugene ShkolyarEugene Shkolyar , Harcharan GillHarcharan Gill , Alan ThongAlan Thong , Jay B. ShahJay B. Shah , Kris PradoKris Prado , Eila C. SkinnerEila C. Skinner , Ash A. AlizadehAsh A. Alizadeh , Joseph C. LiaoJoseph C. Liao , and Maximilian DiehnMaximilian Diehn View All Author Informationhttps://doi.org/10.1097/01.JU.0001009548.76580.ba.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Standard-of-care treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT) followed by adjuvant Bacillus Calmette-Guérin (BCG), yet monitoring response is challenging. Noninvasive biomarkers such as urinary tumor DNA (utDNA) could improve assessment of NMIBC recurrence after BCG. We have developed a liquid biopsy assay called urinary Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq) which has a limit of detection of∼1 part per 10,000 (0.01%). Here, we investigated if uCAPP-Seq utDNA detection can identify responses to BCG in NMIBC. METHODS: We applied tumor-informed uCAPP-Seq to 120 urine specimens from 45 prospectively enrolled high-risk NMIBC patients undergoing BCG induction. GU pathologists annotated tumor and adjacent normal tissue, and DNA was extracted from 1 mm biopsy cores from FFPE blocks. Urine samples were collected prior to TURBT (n=30) and BCG induction (n=45), and at first follow-up after BCG (n=45). The primary endpoint was high-grade recurrence-free survival (HGRFS). RESULTS: uCAPP-Seq analysis identified three major categories of utDNA molecular responses to BCG immunotherapy: 1) utDNA complete response to TURBT (51%; n=23/45 patients), 2) utDNA response to BCG (22%; n=10/45), and 3) no utDNA response (27%; n=12/45) (Fig 1A). Levels of utDNA following BCG were significantly higher in patients with high-grade recurrence (p<0.0001) (Fig 1B). On Kaplan-Meier analysis, patients with persistent utDNA had significantly worse HGRFS compared to patients with responses to TURBT (HR 5.13, 95% CI 1.7-16.5, p=0.0005), and patients with responses to BCG (HR 13.25, 95% CI 4.0-43.7, p=0.0023) (Fig 1C). In patients with utDNA response to BCG, only 10% (n=1/10 patients) experienced high-grade recurrence (Fig 1D). CONCLUSIONS: Detection of utDNA via uCAPP-Seq identifies three types of molecular responses to TURBT and BCG in NMIBC. Molecular response to TURBT and BCG were strongly associated with freedom from high-grade recurrence. About half of patients had complete molecular responses to TURBT, suggesting a significant subset may have been cured by surgery alone. Liquid biopsy detection of utDNA is therefore a promising biomarker for developing personalized treatment strategies for NMIBC. Download PPT Source of Funding: This work is supported by the National Institutes of Health/National Cancer Institute (1R01CA244526) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1169 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information William Y. Shi More articles by this author Kevin J. Liu More articles by this author Mohammad S. Esfahani More articles by this author Joseph G. Schroers-Martin More articles by this author Monica Nesselbush More articles by this author Simon B. Chen More articles by this author Stefan K. Alig More articles by this author Patrick Mullane More articles by this author Kathleen E. Mach More articles by this author Ludimila Trabanino More articles by this author Timothy J. Lee More articles by this author Ihna Yoo More articles by this author Vinh La More articles by this author Gabriela Rodriguez More articles by this author Zachary Kornberg More articles by this author Eugene Shkolyar More articles by this author Harcharan Gill More articles by this author Alan Thong More articles by this author Jay B. Shah More articles by this author Kris Prado More articles by this author Eila C. Skinner More articles by this author Ash A. Alizadeh More articles by this author Joseph C. Liao More articles by this author Maximilian Diehn More articles by this author Expand All Advertisement PDF downloadLoading ...

We appreciate the opportunity to respond to Moraska and Hickner's (MH) latest comments about our microanalytical studies. Response to Letter to the Editor on "Biochemicals Associated With Pain and Inflammation Are Elevated in Sites Near to and Remote From Active Myofascial Trigger Points"Archives of Physical Medicine and RehabilitationPreviewWe appreciate the reply by Shah et al to our initial letter and believe scientific debate to be healthy and necessary, especially given the historic significance the papers have on trigger point research.1,2 Nevertheless, we are unpersuaded by their response regarding our concerns with their methodology and results. Full-Text PDF

You have accessJournal of UrologyBladder Cancer: Non-invasive II (PD30)1 May 2024PD30-03 PREDICTING RESPONSE TO INTRAVESICAL BCG IN HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER USING AN ARTIFICIAL INTELLIGENCE-POWERED PATHOLOGY ASSAY: DEVELOPMENT AND VALIDATION IN AN INTERNATIONAL 12 CENTER COHORT Yair Lotan, Viswesh Krishna, Bryn Launer, Vrishab Krishna, Siddhant Singhi, Jennifer Gordetsky, Jay B. Shah, Thomas Gerald, Eugene Shkolyar, Dickon Hayne, Andrew Redfern, Lisa Spalding, Courtney Stewart, Vikram Narayan, Dattatraya Patil, Vignesh T. Packiam, Anand Rajan, Michael A. O'Donnell, Loic Baekelandt, Mario I. Fernandez, Marcela Schultz, Patrick J. Hensley, Derek B. Allison, John A. Taylor, Ameer Hamza, Vivek Nimgaonkar, Ekin Tiu, Louis J. Vaickus, Snehal Sonawane, Daniel L. Miller, Damir Vrabac, Waleed M. Abuzeid, Anirudh Joshi, Sam S. Chang, and Stephen B. Williams Yair LotanYair Lotan , Viswesh KrishnaViswesh Krishna , Bryn LaunerBryn Launer , Vrishab KrishnaVrishab Krishna , Siddhant SinghiSiddhant Singhi , Jennifer GordetskyJennifer Gordetsky , Jay B. ShahJay B. Shah , Thomas GeraldThomas Gerald , Eugene ShkolyarEugene Shkolyar , Dickon HayneDickon Hayne , Andrew RedfernAndrew Redfern , Lisa SpaldingLisa Spalding , Courtney StewartCourtney Stewart , Vikram NarayanVikram Narayan , Dattatraya PatilDattatraya Patil , Vignesh T. PackiamVignesh T. Packiam , Anand RajanAnand Rajan , Michael A. O'DonnellMichael A. O'Donnell , Loic BaekelandtLoic Baekelandt , Mario I. FernandezMario I. Fernandez , Marcela SchultzMarcela Schultz , Patrick J. HensleyPatrick J. Hensley , Derek B. AllisonDerek B. Allison , John A. TaylorJohn A. Taylor , Ameer HamzaAmeer Hamza , Vivek NimgaonkarVivek Nimgaonkar , Ekin TiuEkin Tiu , Louis J. VaickusLouis J. Vaickus , Snehal SonawaneSnehal Sonawane , Daniel L. MillerDaniel L. Miller , Damir VrabacDamir Vrabac , Waleed M. AbuzeidWaleed M. Abuzeid , Anirudh JoshiAnirudh Joshi , Sam S. ChangSam S. Chang , and Stephen B. WilliamsStephen B. Williams View All Author Informationhttps://doi.org/10.1097/01.JU.0001008848.77629.6f.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intravesical BCG is first-line therapy for high-risk non-muscle invasive bladder cancer (HR NMIBC) but there are few markers to identify those likely to recur or progress. We developed and validated deep learning-based histologic assays that extract interpretable features from BCG-naïve transurethral resection of bladder tumor (TURBT) digitized pathology slides to predict recurrence and progression following BCG. METHODS: Pre-intravesical BCG TURBT-derived digital whole slide images (WSI) and clinical data were obtained for BCG-naïve AUA HR NMIBC cases diagnosed between 2000-2022 and treated with adequate BCG therapy from 12 academic centers. WSI were analyzed through a segmentation and geometric feature extraction pipeline. Features associated with high-grade recurrence free survival (hgRFS), progression free survival (PFS; upstaging and/or muscle invasion), progression to muscle invasion (mPFS) and BCG response were defined in the development cohort. Feature-locked assays were then tested on an independent validation cohort. Cases were classified into high risk (upper 20%, "AI High [AI-H]") and low risk (bottom 80%, "AI Low [AI-L]") of recurrence or progression, and on presence or absence of the BCG Unresponsive Biomarker (BUB). RESULTS: 1071 HR NMIBC cases (development: 311, validation: 760) with median follow-up of 34 months were included (HGTa:33.3%, HGT1:54.4%; any CIS:31.6%). In the validation set, patients in the AI-H group had significantly inferior hgRFS, PFS and mPFS versus the AI-L group (HR 2.32, 3.08, 3.37, p<0.001, respectively) (Fig 1). FDA-defined BCG unresponsive status was 1.8-fold higher in BUB present versus BUB absent cases. AI biomarkers were independent of age, sex, smoking status, grade, T-stage, presence of CIS and multifocality across all endpoints (p<0.001). CONCLUSIONS: In this study, we validated AI-based histologic assays that accurately identify cases of HR NMIBC that are at significantly higher risk of recurrence, progression, and development of BCG unresponsive status. These assays may aid clinical decision-making related to use of intravesical BCG versus alternative therapies in the treatment of NMIBC. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e625 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yair Lotan More articles by this author Viswesh Krishna More articles by this author Bryn Launer More articles by this author Vrishab Krishna More articles by this author Siddhant Singhi More articles by this author Jennifer Gordetsky More articles by this author Jay B. Shah More articles by this author Thomas Gerald More articles by this author Eugene Shkolyar More articles by this author Dickon Hayne More articles by this author Andrew Redfern More articles by this author Lisa Spalding More articles by this author Courtney Stewart More articles by this author Vikram Narayan More articles by this author Dattatraya Patil More articles by this author Vignesh T. Packiam More articles by this author Anand Rajan More articles by this author Michael A. O'Donnell More articles by this author Loic Baekelandt More articles by this author Mario I. Fernandez More articles by this author Marcela Schultz More articles by this author Patrick J. Hensley More articles by this author Derek B. Allison More articles by this author John A. Taylor More articles by this author Ameer Hamza More articles by this author Vivek Nimgaonkar More articles by this author Ekin Tiu More articles by this author Louis J. Vaickus More articles by this author Snehal Sonawane More articles by this author Daniel L. Miller More articles by this author Damir Vrabac More articles by this author Waleed M. Abuzeid More articles by this author Anirudh Joshi More articles by this author Sam S. Chang More articles by this author Stephen B. Williams More articles by this author Expand All Advertisement PDF downloadLoading ...

Purpose:Patients treated with radical cystectomy experience a high rate of postoperative complications and frequent hospital readmissions. We sought to explore the utility of the Care Assessment Need (CAN) score, derived from electronic health data, to estimate the risk of these adverse clinical outcomes, thereby aiding patient counseling and informed treatment decision-making.Materials and Methods:We retrospectively examined data from 982 patients with bladder cancer who underwent radical cystectomy between 2013 and 2018 within the national Veterans Health Administration system. We tested for associations between the preoperative CAN score and length of stay, discharge location, and readmission rates.Results:We observed a correlation between higher CAN scores and longer hospital stays (adjusted relative risk = 1.03 [95% CI: 1.02-1.05]). An increased CAN score was also linked to greater odds of discharge to a skilled nursing facility or death (adjusted odds ratio = 1.16 [95% CI: 1.06-1.26]). Furthermore, the score was associated with hospital readmission at both 30 and 90 days postdischarge (adjusted HR = 1.03 [95% CI: 1.00-1.07] and 1.04 [95% CI: 1.00-1.07], respectively).Conclusions:The CAN score is associated with length of hospital stay, discharge to a skilled nursing facility, and readmission within 30 and 90 days after radical cystectomy. These findings highlight the potential of health care systems leveraging electronic health records for automatically calculating multidimensional tools, such as the CAN score, to identify patients at risk of adverse clinical outcomes after radical cystectomy.

PURPOSE:There are few markers to identify those likely to recur or progress after treatment with intravesical bacillus Calmette-Guérin (BCG). We developed and validated artificial intelligence (AI)-based histologic assays that extract interpretable features from transurethral resection of bladder tumor digitized pathology images to predict risk of recurrence, progression, development of BCG-unresponsive disease, and cystectomy. MATERIALS AND METHODS:Pre-BCG resection-derived whole-slide images and clinical data were obtained for high-risk nonmuscle-invasive bladder cancer cases treated with BCG from 12 centers and were analyzed through a segmentation and feature extraction pipeline. Features associated with clinical outcomes were defined and tested on independent development and validation cohorts. Cases were classified into high or low risk for recurrence, progression, BCG-unresponsive disease, and cystectomy. RESULTS:Nine hundred forty-four cases (development: 303, validation: 641, median follow-up: 36 months) representative of the intended use population were included (high-grade Ta: 34.1%, high-grade T1: 54.8%; carcinoma in situ only: 11.1%, any carcinoma in situ: 31.4%). In the validation cohort, "high recurrence risk" cases had inferior high-grade recurrence-free survival vs "low recurrence risk" cases (HR, 2.08, P < .0001). "High progression risk" patients had poorer progression-free survival (HR, 3.87, P < .001) and higher risk of cystectomy (HR, 3.35, P < .001) than "low progression risk" patients. Cases harboring the BCG-unresponsive disease signature had a shorter time to development of BCG-unresponsive disease than cases without the signature (HR, 2.31, P < .0001). AI assays provided predictive information beyond clinicopathologic factors. CONCLUSIONS:We developed and validated AI-based histologic assays that identify high-risk nonmuscle-invasive bladder cancer cases at higher risk of recurrence, progression, BCG-unresponsive disease, and cystectomy, potentially aiding clinical decision making.

BACKGROUND:Overuse of stress ulcer prophylaxis is prevalent globally despite guidelines leading to the added cost, especially the intravenous proton pump inhibitor (IVPPI). This study aims to analyze the prevalence of such overuse and be aware of rational use which may help develop local guidelines.METHODS:This study analyzed the prospectively collected data on IVPPI use in adult patients in general wards of medicine and surgery at Patan Hospital, Patan Academy of Health Sciences, Nepal, from April-Jun 2022. Ethical approval was obtained. Variables analyzed were the patient's age, gender, history of peptic ulcer disease, risk for stress ulcer and gastrointestinal bleeding, the status of nil per os (NPO ≥12 hours), appropriate use of IVPPI, and cost.RESULTS:Prevalence of IVPPI use was 36.24% (274/756 admissions), surgery 39.45(189/479), medicine ward 30.68% (85/277). The mean age was 43.1 ±18.6 years, males 113(41.2%), surgery 189 (69%). Inappropriate overuse in 253(92.3%, significantly more in surgery-182 than medicine-7, p=0.001. Appropriate use was in 21 (7.7%, i.e., NPO-15, NPO + gastrointestinal bleed, and NPO + non steroid anti-inflammatory drugs each 3).CONCLUSIONS:Prevalence of IVPPI use was 36.24%. Inappropriate overuse of IVPPI was high (92.2%, 253/274), more in surgery. The nil per os status was the main reason for appropriate use of IVPPI.

PURPOSE:While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort.MATERIALS AND METHODS:We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival.RESULTS:Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1).CONCLUSIONS:In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.