Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:Non-muscle-invasive bladder cancer (NMIBC) patients treated with additional bacillus Calmette-Guérin (BCG) may become unresponsive to BCG. Recently, sequential intravesical gemcitabine and docetaxel (gem/doce) are being used for NMIBC. This study aims to compare oncologic outcomes between sequential intravesical gem/doce versus additional BCG in patients with BCG-unresponsive NMIBC. METHODS:Data were collected from ten academic institutions on patients with BCG-unresponsive NMIBC based on the Food and Drug Administration guidelines. Information on high-grade recurrence-free (HGRFS), progression-free (PFS), cystectomy-free (CFS), metastasis-free (MFS), cancer-specific (CSS), and overall (OS) survival was collected. The Kaplan-Meier method and Cox proportional hazard ratios (HRs) were used to determine differences in oncologic outcomes between the Gem/Doce and BCG groups. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Of 299 total patients, 204 underwent additional BCG treatment at the time of BCG unresponsiveness and 95 underwent gem/doce treatment. Rates of PFS (HR 2.6, 95% confidence interval [CI] 1.1-5.0, p = 0.03), CFS (HR 2.0, 95% CI 1.2-3.4, p = 0.01), and CSS (HR 3.7, 95% CI 1.1-12.3, p=0.03) were higher in patients receiving gem/doce. HGRFS, MFS, and OS were similar between both groups. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:The findings from this study suggest that intravesical gem/doce is associated with lower rates of progression than additional BCG in patients with BCG-unresponsive NMIBC who decline or are ineligible for cystectomy. PATIENT SUMMARY/RESULTS:In this report, we looked at outcomes between patients with noninvasive bladder cancer who were treated with additional bacillus Calmette-Guérin (BCG) or gemcitabine-docetaxel combination after not responding to primary BCG therapy. We found that intravesical gemcitabine-docetaxel was associated with fewer progression events than additional salvage BCG therapy.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Current data on bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) do not differentiate outcomes by clinical stage. The purpose of this study is to investigate the role of tumor stage in oncologic outcomes in BCG-unresponsive NMIBC undergoing bladder-sparing therapies. METHODS:Demographic and outcome data for patients with BCG-unresponsive NMIBC were reviewed at ten institutions. The Kaplan-Meier method was used to determine survival differences between the T1 ± carcinoma in situ (CIS), Ta alone, and CIS ± Ta groups. Exploratory analyses were conducted as follows: (1) T1 alone versus Ta alone versus CIS ± T1/Ta and (2) T1/Ta alone versus CIS ± T1/Ta. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Among 401 patients, 137 (34%) were T1 ± CIS, 104 (26%) Ta alone, and 160 (40%) CIS ± Ta. Disease progression (p < 0.001), metastasis (p < 0.001), and bladder cancer mortality (p = 0.009) were increased in the T1 ± CIS group versus the Ta alone and CIS ± Ta groups. Cystectomy occurred most often in the CIS ± Ta and T1 groups (p = 0.002). Similar increases were noted in progression (p < 0.001), metastasis (p < 0.001), and bladder cancer mortality (p = 0.004) in T1 alone patients versus the Ta alone and CIS ± T1/Ta groups. There were no differences in outcomes between the T1 alone and T1 + CIS groups. No significant differences in metastasis, bladder cancer mortality, or all-cause mortality were noted when comparing papillary disease only with any CIS. The primary limitation of this study is likely a selection bias due to the retrospective nature of the cohort. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Presence of T1 disease is generally associated with worse oncologic outcomes compared with Ta or CIS. T1 and Ta should not be grouped together during comparison with CIS. Radical cystectomy appears largely driven by the presence of CIS.

INTRODUCTION/BACKGROUND:Treatment patterns for patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy (RC) are inconsistently reported. We retrospectively described demographic, clinical, and treatment characteristics for these patients and assessed their clinical outcomes. PATIENTS AND METHODS/METHODS:Medical charts of patients with BCG-unresponsive high-risk NMIBC (carcinoma in situ [cohort A] or T1/high-grade Ta [cohort B]) who were ineligible for or declined RC documented between January 1, 2011, and December 31, 2018, at 15 academic centers were reviewed. Primary objectives were to characterize demographic, clinical, and nonsurgical treatment characteristics. Secondary objectives included assessing real-world progression-free survival (rw-PFS) from muscle-invasive/metastatic disease, rw-PFS from worsening grade or stage, real-world complete response rate (rw-CRR) in cohort A, real-world event-free survival (rw-EFS) from high-risk NMIBC in cohort B, and overall survival. RESULTS:The study included 129 patients (cohort A, n = 57; cohort B, n = 72). Median age was 72.0 years (interquartile range, 64.0-80.0). Most patients were male (72.1%) and current/former smokers (69.8%). Median follow-up was 32.1 months (interquartile range, 20.7-47.6). BCG rechallenge with or without interferon-α (63.6%) was the most commonly utilized first nonsurgical therapy, followed by intravesical mitomycin C with or without electromotive drug administration or thermochemotherapy (15.5%), and intravesical valrubicin (10.9%); among those who received BCG rechallenge alone, 54.8% later received a non-BCG therapy in ≥ 2 subsequent treatments. 36-month rate for rw-PFS from muscle-invasive/metastatic disease was 73.5%, 66.8% for rw-PFS from worsening grade/stage, and 82.5% for overall survival. In cohort A, 6-month rw-CRR was 22.2%. In cohort B, 36-month rw-EFS rate from high-risk NMIBC was 50.2%. CONCLUSION/CONCLUSIONS:After BCG-unresponsive disease, most patients with high-risk NMIBC received BCG rechallenge with or without other therapies, and > 25% experienced disease progression within the first 3 years. Effective bladder-sparing options for BCG-unresponsive NMIBC are needed. CLINICAL TRIAL REGISTRATION/BACKGROUND:N/A.

OBJECTIVE:To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS/METHODS:Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS:Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION/CONCLUSIONS:In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

INTRODUCTION/UNASSIGNED:Balancing surgical margins and functional outcomes is crucial during radical prostatectomy for prostate cancer. Stimulated Raman Histology (SRH) is a novel, real-time imaging technique that provides histologic images of fresh, unprocessed, and unstained tissue within minutes, which can be interpreted by either humans or artificial intelligence. METHODS/UNASSIGNED:Twenty-two participants underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with intraoperative SRH surgical bed assessment. Surgeons resected and imaged surgical bed tissue using SRH and adjusted treatment accordingly. An SRH convolutional neural network (CNN) was developed and tested on 10 consecutive participants. The accuracy, sensitivity, and specificity of the surgical team's interpretation were compared to final histopathological assessment. RESULTS/UNASSIGNED:A total of 121 SRH periprostatic surgical bed tissue (PSBT) assessments were conducted, an average of 5.5 per participant. The accuracy of the surgical team's SRH interpretation of resected PSBT samples was 98%, with 83% sensitivity, and 99% specificity. Intraoperative SRH assessment identified 43% of participants with a pathologic positive surgical margin intraoperatively. PSBT assessment using the CNN demonstrated no overlap in tumor probability prediction between benign and tumor infiltrated samples, mean 0.30% (IQR 0.10-0.43%) and 26% (IQR 18-34%, p<0.005), respectively. CONCLUSION/UNASSIGNED:SRH demonstrates potential as a valuable tool for real-time intraoperative assessment of surgical margins during RALP. This technique may improve nerve-sparing surgery and facilitate decision-making for further resection, reducing the risk of positive surgical margins and minimizing the risk of recurrence. Further studies with larger cohorts and longer follow-up periods are warranted to confirm the benefits of SRH in RALP.

OBJECTIVE:To evaluate predictors of contralateral clinically significant prostate cancer (csPCa) in men with biopsy-proven unilateral lesions on magnetic resonance imaging (MRI). METHODS:We retrospectively identified men with no prior diagnosis of PCa with unilateral biopsy-confirmed csPCa within PI-RADS 2-5 lesions within our institutional biopsy database. Multivariate logistic regression was used to identify clinical predictors of contralateral disease. RESULTS:Four hundred ninety men met study inclusion criteria, of which 385 men (78.6%) had no contralateral csPCa and 105 men (21.4%) had contralateral csPCa (Fig. 1). Prior negative biopsy (OR 0.34 [0.14, 0.75], P = .012), prostate-specific antigen density (OR 18.8 [2.77, 249], P = .017), and tumor location in the transverse plane ("Posterior": OR 1.93 [1.02, 3.87], P = .048; "Throughout Transverse Plane": OR 6.56 [2.26, 19.6], P < .001) were significantly associated with contralateral csPCa in multivariate logistic regression models. However, there appear to be no attributes within the MRI-targeted tumor that reliably predict contralateral csPCa (Table 2). CONCLUSION/CONCLUSIONS:Approximately 20% of men with unilateral MRI findings and csPCa on targeted biopsy were found to have contralateral csPCa on systematic biopsy (SB). Prior negative biopsy was associated with a decreased odds of contralateral csPCa. Prostate-specific antigen density and tumor in the posterior aspect of or throughout the transverse plane were associated with increased odds of contralateral csPCA. Consideration of these clinical factors may afford an opportunity to only use SB in cases in which the odds of contralateral csPCa are high.

Urine leak (UL) and vascular complications (VC), i.e., pseudoaneurysms and arteriovenous fistulas are well-described complications of robotic-assisted partial nephrectomy (RAPN). Historically, UL incidence ranges from 0.3 to 17% and VC from 0.8 to 5.6%. We report the contemporary experience of UL and VC from a single, high-volume center in cases of RAPN. 447 patients were identified from an IRB-approved Renal Tumor Database of 2174 cases who underwent RAPN from 1/2017 to 5/2023. VC occurred in 9 cases (4 pseudoaneurysms, 1 AV fistula, 4 concurrent AV fistula/pseudoaneurysm), UL occurred in 9 (2.0%), and there was one concurrent case of VC and UL. Collecting-system entry occurred in five VC cases and five UL cases. For VCs, the median nephrometry score and maximal tumor diameter was 8 (IQR 3.0) and 3.8 (0.9) cm, respectively, and 8 (3.0) and 3.7 (1.1) cm for UL cases, respectively. Most complications occurred with tumors ≤ 4 mm from the collecting system (n = 7 VC, n = 6 UL). VCs presented after 18 (6.0) days, 6 with gross hematuria; 3 required clot irrigation, 1 required continuous bladder irrigation, and 8 required embolization. No patients required postoperative transfusion. Patients with UL presented after a median of 1 (12) day, with 5 cases detected by elevated creatinine in drain fluid and the remainder detected on routine ultrasound. The duration of UL was 13 (41) days with only 2 cases requiring stenting and one case requiring a drainage catheter. No patients required kidney re-operation or removal. Our rate of VC and UL following RAPN are low and consistent with other contemporary series. Complications occurred in patients with high nephrometry scores or tumors located close to the collecting system. Both complications generally present early and can be managed without kidney re-operation or removal.

PURPOSE/UNASSIGNED:To evaluate the efficacy and safety of UGN-102 chemoablation for the primary treatment of patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS/UNASSIGNED:ENVISION is an ongoing, multinational, single-arm, Phase 3 study in patients with a biopsy-proven recurrence of untreated low-grade intermediate-risk nonmuscle-invasive bladder cancer. Patients received 6 weekly intravesical instillations of UGN-102 (mitomycin; outpatient setting) and were evaluated at 3 months. Patients achieving complete response (CR) (negative cystoscopic examination, cytology, and for-cause biopsy) were surveilled regularly until recurrence, progression, or death. Patients who remain disease-free will be followed up to 5 years, and further results will be reported in the future. RESULTS/UNASSIGNED:Of 240 patients enrolled, 228 (95%) received all 6 planned doses; 191 (79.6%; 95% CI: 73.9, 84.5) achieved CR at 3 months, with an 82.3% (95% CI: 75.9, 87.1) probability of response 12 months later. Median duration of response was not estimable over a median 13.9-month follow-up period. The most common adverse events (≥5.0% of patients) were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention; generally mild/moderate and resolved/resolving. Serious adverse events were observed in 29/240 (12.1%), 2 were treatment-related (urinary retention/urethral stenosis), both resolved. CONCLUSIONS/UNASSIGNED:Primary chemoablation with UGN-102 in patients with recurrent low-grade-intermediate-risk-nonmuscle-invasive bladder cancer resulted in a 79.6% CR rate. Patients achieving a CR had an 82.3% likelihood of remaining disease-free 1 year later. The benefit-risk profile was favorable, supporting UGN-102 as a non-surgical alternative for transurethral resection of bladder tumors in this patient population. Limitations of this study included lack of tumor sizing after the diagnostic biopsy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT05243550.

OBJECTIVES/OBJECTIVE:To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS/METHODS:From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS:A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION/CONCLUSIONS:In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.