Zganjar, Andrew

703 Background: The association of circulating tumor DNA (ctDNA) reduction with treatment response has been investigated across multiple malignancies. This study aims to assess the impact of ctDNA response on survival outcomes in patients receiving enfortumab-pembrolizumab (EV-P). Methods: We identified 32 patients with advanced urothelial carcinoma who received EV-P and had ≥2 ctDNA assessments with ≥1 detectable level. Deep molecular response was defined as >2-log reduction from highest ctDNA detection. Radiographic progression was determined from radiology reports documenting progression by RECIST criteria. Kaplan Meier analyses were performed to compute Hazard Ratios (HR) with 95% confidence intervals (CI) for radiographic progression free survival (rPFS), defined as time from treatment start to radiographic progression or death and overall survival (OS) defined as time from treatment start to death were computed. Log-rank tests were performed to compare PFS and OS in patients with deep molecular response to those without response. A p-value <0.05 indicated a statistically significant association with response. Results: Thirty-two patients were included (median age 71 years; range 39–90). Median follow-up was 10.6 months. At cutoff (10/1/2025), 26 patients were alive and 6 had died. Seventeen (53%) achieved a ≥2-log ctDNA reduction (responders), while 15 (47%) did not (non-responders). Progression-free survival was significantly longer in responders (log-rank P < 0.001); median PFS was 5.9 months (95% CI 2.4–NR) in non-responders and not reached in responders (HR 0.09, 95% CI 0.02–0.44; P = 0.0026). Median overall survival was 12.7 months (95% CI 10.0–NR) in non-responders versus not reached in responders (log-rank P = 0.011; HR 0.11, 95% CI 0.01–0.88; P = 0.037). At cutoff, 94% of responders and 67% of non-responders were alive. Conclusions: Achieving a >2-log decrease in ctDNA during EV + Pembrolizumab therapy was significantly associated with improved progression free and overall survival. These findings support ctDNA kinetics as a potential early biomarker of response warranting prospective validation. Clinical outcomes by >2-log ctDNA reduction status. Endpoint > 2-log drop (n = 17 ≤ 2-log drop (n = 15) Log-rank p Median (mo) ≤ 2-log > 2-log HR (95% CI) P C-index PFS 2 events (12%) 10 events (67%) 0.0002 5.9 (2.4–NA) NR 0.09 (0.02–0.44) 0.0026 0.77 OS 1 event (6%) 6 events (40%) 0.011 12.7 (10.0–NA) NR 0.11 (0.01–0.88) 0.037 0.73

Introduction: Robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (PLND) represents the gold standard surgical treatment for high-risk localized prostate cancer. PLND carries the risk of lymphocele formation, which can lead to complications such as deep vein thrombosis (DVT), infection, and voiding dysfunction. Many techniques have been described to minimize lymphocele formation, yet no method has seen widespread use or been described as sutureless. The objective of this study is to describe the novel, sutureless peritoneal window (PWIN) technique and assess its efficacy in lymphocele prophylaxis for extended PLND. Methods: This was a retrospective review of patients with high-risk prostate cancer undergoing RARP with extended PLND by a single surgeon from 2018 to 2024. PLND was carried out in the usual manner with bipolar cautery. PWIN technique is performed by excising a 3 × 5 cm PWIN over the lymphadenectomy bed to maintain lymphatic communication with the abdominal cavity. The primary outcome was a comparison between the incidence of symptomatic lymphoceles (SLs) with PWIN vs standard technique. SLs were defined as lymphoceles presenting with pain, DVT, voiding dysfunction, or infectious symptoms. Patients with asymptomatic lymphoceles were excluded. Results: Our study included 199 patients who underwent RARP with extended PLND. There were 46 patients (23.1%) in the standard approach group and 153 patients (76.9%) in the PWIN group. We identified 5/46 (10.9%) SLs in the standard technique, which were significantly higher than the 3/153 (2.0%) observed in the PWIN group (p = 0.017). There was no difference between the standard and PWIN cohorts regarding symptomology or treatment of their lymphocele. Conclusion: This study describes a novel, sutureless PWIN technique that significantly decreases SL after extended PLND. This technique offers a practical, time-efficient, and cost-effective alternative for lymphocele prevention. Future prospective studies are warranted to validate these findings.

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].