Nguyen, Mimi Thi

716 Background: Nadofaragene firadenovec is an FDA-approved gene therapy for Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) with promising clinical trial results. However, real-world post-marketing efficacy or safety data remain lacking. We evaluated complete response rates and safety in a multisite experience. Methods: Per IRB protocol, we analyzed patients treated with nadofaragene firadenovec for BCG-unresponsive NMIBC across three Mayo Clinic sites. Outcomes included complete response (CR), high-grade recurrence-free survival (HGRFS), cystectomy-free survival (CFS), overall survival (OS), and adverse events (AEs). CR and HGRFS were reported for patients with carcinoma in situ (CIS) and patients with Ta/T1 without CIS respectively. Failure to retain was defined as any medication loss, including leakage around the catheter or early voiding. Results: Between November 2023 and October 2024, 45 patients were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Fifteen patients with follow-up less than 6 months and one patient with extensive metastatic disease identified one week after first instillation were excluded from efficacy analysis. Our efficacy-evaluable population of 29 patients with median follow-up of 8.2 months is summarized in the Table. CR/HGRFS at 3 and 6 months was 72% and 62% respectively. CFS was 94% and OS was 100% at 6 months. Three patients experienced disease progression during follow-up: one to T1, another to T2, and a third with metastases to the abdomen and lungs. A separate patient developed a metachronous upper tract urothelial carcinoma (pT2) without bladder recurrence. Bladder spasms (62%) and failure to retain (31%) were the most common AEs. Most AEs were low-grade, although four (9%) patients had grade 3 events (fatigue, fever, and dizziness). No grade 4-5 AEs were reported. Conclusions: Early real-world data demonstrates encouraging clinical complete response rates in patients with BCG-unresponsive NMIBC and a favorable safety profile. Further investigation with larger cohorts and longer follow-up is warranted. Evaluable patients (N=29) CIS cohort (N=15) Ta/T1 only cohort (N=14) Prior pembrolizumab (N=9) Prior intravesical chemotherapy (N=16) Age, years 72 (67-77) 74 (69-77) 71 (67-77) 69 (67-78) 73 (67-81) Elixhauser Index 5 (4-6) 5 (4-7) 5 (4-6) 5 (3-5) 5 (3-6) Prior BCG instillations 12 (10-14) 12 (12-15) 11 (8-13) 12 (12-12) 12 (11-13) Prior intravesical chemotherapy among recipients 6 (6-11) 6 (6-10) 6 (6-11) 10 (7-12) 6 (6-11) Prior pembrolizumab doses among recipients 7 (4-8) 8 (7-8) 4 (4-4) 7 (4-8) 8 (5-8) Follow-up, months 8.2 (6.9-9.5) 7.6 (6.9-9.5) 8.5 (6.9-9.4) 9.1 (8.0-10.1) 8.6 (6.7-9.9) 3-month CR/HGRFS 72% [53-87] 73% [45-92] 71% [42-92] 67% [30-93] 56% [30-80] 6-month CR/HGRFS 62% [42-79] 67% [38-88] 57% [29-82] 44% [14-79] 44% [20-70] Data are median (IQR) or % [95% CI].

Background The American Urological Association (AUA)/Society of Urology Oncology (SUO) guidelines recommend a repeat transurethral resection of bladder tumor (TURBT) for high-risk, non-invasive (HR Ta) nonmuscle invasive bladder cancer (NMIBC) patients. The evidence base for this recommendation is weak (grade C) and fraught with methodological shortcomings, such as the lack of adjuvant intravesical Bacillus Calmette Guerin (BCG) and single-center study designs. Objective We sought to evaluate the effect of repeat TURBT on recurrence-free survival at a population level in HR Ta NMIBC patients who completed BCG induction therapy. Methods High-grade Ta NMIBC patients who underwent TURBT for a ≥5 cm tumor were identified within the SEER-Medicare database. All patients completed induction BCG and were stratified into two groups: repeat TURBT within eight weeks of initial TURBT and a group without repeat TURBT (control group). The primary endpoint was the 3-year high-risk recurrence rate. Results A cohort of 604 patients was identified, with 93 (15.4%) undergoing a repeat TURBT within eight weeks of initial TURBT and 511 (84.6%) without a repeat TURBT. Patient demographic and clinical characteristics were similar overall. No significant difference in the 3-year recurrence rate was noted (repeat TURBT: 20.4% vs. control group: 15.7%, p = 0.25). After adjusting for demographic and clinical characteristics, no association between repeat TURBT and 3-year high-risk recurrence was observed (HR (95% CI): 1.27 (0.76, 2.11); p = 0.36). Conclusion Although our study contains several major limitations, our results suggest that repeat TURBT in large volume HG Ta NMIBC treated with induction BCG therapy was not associated with improved high-risk recurrence-free survival.

Background: Postoperative stress urinary incontinence (SUI) after Holmium Laser Enucleation of the Prostate (HoLEP) has improved with the early apical release (EAR) technique. However, some patients develop SUI despite using EAR HoLEP. The aim of this study is to investigate whether a novel classification of the external sphincter is correlated with postoperative SUI. Methods: The data of 98 patients who underwent EAR HoLEP for benign prostatic hyperplasia were prospectively analyzed. We propose a novel endoscopic classification of external sphincter appearance after HoLEP graded from 0 (best preserved) to 3 (most degraded). Patients were followed for 6 months postoperatively and administered validated questionnaires. A logistic regression was performed to compare moderate SUI rates at sphincter grade 3, controlling for age, obesity, catheter dependency, and grams resected at 6 weeks and 3 months. Results: The sphincter grades included 6 grade 0, 47 grade 1, 30 grade 2, and 15 grade 3. Patients were divided into a group without SUI ( n = 51), and a group with SUI ( n = 47) at 6 weeks postoperatively by International Consultation on Incontinence Questionnaire (ICIQ). Patients with reported SUI on ICIQ were more likely to have sphincter grades ≥2 at 6 weeks (p= 0.001) and 3 months ( p < 0.0001). At 6 months, persistent SUI was associated with sphincter grade 3 ( p < 0.0001). Logistic regression demonstrated that sphincter grade 3 was associated with clinically significant SUI at 3 months ( p < 0.01). Conclusions: Lower sphincter grades are associated with improved return of continence after EAR HoLEP.