Lyon, Timothy D.

Background: The comparative effectiveness of robotic-assisted versus conventional minimally invasive (“straight stick”) approaches across multiple solid organ malignancies remains incompletely defined, limiting evidence-based operative platform selection. Study Design: Patients undergoing minimally invasive primary tumor resection for 17 solid organ cancers were identified in the National Cancer Database (2010–2022) and stratified by robotic-assisted versus straight stick approach. The primary endpoint was conversion to open surgery. Secondary endpoints included short-term outcomes and oncologic/technical metrics. Multivariable logistic and negative binomial regression models were used to estimate adjusted associations. Results: Among 2,258,360 patients, 1,339,482 (59.3%) underwent robotic-assisted resection. Robotic surgery was associated with lower adjusted conversion rates compared with straight stick approaches (6.1% vs 13.6%, p<0.001), a finding consistent across all organ sites. Robotic approaches yielded approximately one additional lymph node on average after adjustment. Length of stay, 90-day mortality, and negative margin rates were overall similar between groups, with variation by disease site. Conclusions: In this large national cohort, robotic-assisted resection for solid organ malignancies was more frequently utilized and associated with lower conversion rates and modestly higher lymph node yield compared with straight stick approaches. These findings support consideration of robotic platforms to reduce conversion risk, although equivalence in other short-term outcomes and potential residual confounding warrant cautious interpretation.

A 79-year-old man was referred for evaluation of a recurrent neoplasm of the left scrotum.

776 Background: There continues to be a significant unmet need for safe, effective, and bladder sparing treatment options for patients with non-muscle invasive bladder cancer (NMIBC). TARA-002 is a lyophilized biological preparation for intravesical instillation containing inactivated cells of Streptococcus pyogenes (Group A, type 3) Su strain. TARA-002 rapidly enters cancer cells, activating TLR2 and NOD2 to trigger innate immunity, inflammation, and potential immunogenic cell death. ADVANCED-2 (NCT05951179) is an ongoing Phase 2, open-label study to evaluate the safety and efficacy of intravesical TARA-002 in adults ≥ 18 years with high-grade (HG)-NMIBC CIS (± Ta/T1). Preliminary results showed promising complete response (CR) rates and durable responses in patients with HG NMIBC treated with TARA-002 (Jayram et al. AUA 2025). This abstract presents pooled safety data of TARA-002 from the BCG-naïve cohort and BCG-unresponsive cohort of the ADVANCED-2 study. Methods: The ADVANCED-2 study includes 2 cohorts of BCG-naïve (Cohort A) and BCG-unresponsive (Cohort B) participants. Key exclusion criteria include penicillin allergy; history of ≥ T2 bladder cancer, nodal, or metastatic disease; and concomitant prostatic or upper tract urothelial involvement. Each participant is treated with TARA-002 to receive induction (6 weekly doses), reinduction (if persistent disease at 3 months), and maintenance (through 24 months). Response is assessed every 3 months for 2 years. Long-term follow-up is conducted up to 60 months. Safety is monitored throughout the study. Results: As of 07-October-2025, 60 participants (median age: 74; range: 45 to 92), have been enrolled and exposed to TARA-002: 31 BCG-naïve (Cohort A) and 29 BCG-unresponsive (Cohort B). In both cohorts, 18/60 (30.0 %) participants reported drug-related treatment emergent adverse events (TEAEs). Related TEAEs were Grade 1 (18/60; 30.0%) and Grade 2 (3/60; 5.0%), with no reported Grade 3-5 related TEAEs. Commonly reported related TEAEs (≥ 5%) included bladder spasm (10.0%), dysuria (13.3%), fatigue (6.7%), and micturition urgency (6.7%). Most TEAEs were mild and transient. In both cohorts, 10/60 (16.7%) experienced serious AEs (SAEs); 4/60 (6.7%) were Grade 2 and 9/60 (15.0%) were Grade 3. No participants experienced drug-related SAEs or drug-related TEAEs leading to withdrawal or death. Conclusions: TARA-002 monotherapy was well tolerated, thus demonstrating a favorable tolerability profile to date for the treatment of BCG-naïve and BCG-unresponsive HG NMIBC with CIS (±Ta/T1). TARA-002 has a promising safety profile as a bladder-sparing treatment in HG NMIBC across BCG exposure status. Updated safety data will be provided based on evaluable time points at the time of the presentation. Clinical trial information: NCT05951179 .

755 Background: Patients with High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer have limited treatment options. The US FDA approved treatments for BCG-UR patients with CIS, but additional bladder-sparing therapies are needed, especially for the BCG-UR papillary-only population. Cretostimogene is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Rb-E2F pathway alterations. This releases tumor-specific antigens, initiating an anti-tumor immune response, further amplified by the GM-CSF transgene. The BOND-003 Cohort P study (NCT04452591) is a single-arm clinical trial assessing the efficacy and safety of intravesical cretostimogene in HR, papillary-only, BCG-UR NMIBC patients. Methods: Eligibility criteria include age ≥18 years, ECOG PS of 0-2, and histologically confirmed BCG-UR HG Ta/T1 papillary disease without CIS within 90 days of study enrollment as verified per central pathology review. Patients had no visible evidence of residual bladder cancer before treatment. Intravesical cretostimogene is instilled for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 36. Re-induction is permitted at 3 months for patients with HG Ta or CIS. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and mandatory biopsy directed at prior tumor locations at Month 12, with centralized review of pathologic samples. Endpoints include HG-RFS, HG-EFS, PFS, and safety. The study has completed enrollment. Results: A total of 56 patients who received treatment with cretostimogene are evaluated based on data from September 1, 2025 cut off. At baseline, 76.7% of patients are 65 years or older, 21.4% are female, 64.3% have HG Ta, and 35.7% have HG T1 papillary NMIBC. Kaplan-Meier estimates of HG-RFS at 6- and 9-months are 84.6% (95% CI 73.1 - 96.1%) and 80.4% (95% CI 66.8-94.0%), respectively. No patients have undergone a radical cystectomy. One patient progressed to metastatic disease despite a clinical complete response in the bladder. Cretostimogene demonstrates a favorable safety profile, with most adverse events localized to low grade bladder symptoms. There are no serious treatment-related adverse events and no discontinuations related to cretostimogene. To date, no patients have required a dose delay or missed a dose due to a related adverse event. There have been no deaths related to study treatment. Further, updated data will be presented. Conclusions: These results demonstrate consistent efficacy and a well-tolerated safety profile. Mature data with longer term follow-up will build upon these promising findings and will inform future treatment approaches with cretostimogene. Clinical trial information: NCT04452591 .

743 Background: Although patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) have several emerging therapeutic options, there remains a clinical unmet need to improve efficacy, durability of response, and tolerability while obviating the need for radical cystectomy. TARA-002 is a lyophilized biological preparation for intravesical instillation containing inactivated cells of Streptococcus pyogenes (Group A, type 3) Su strain. TARA-002 rapidly enters cancer cells, activating TLR2 and NOD2 to trigger the innate immune response, inflammation, and potential immunogenic cell death. Herein we present interim safety and efficacy data of TARA-002 from the BCG-unresponsive cohort of the ongoing ADVANCED-2 study (NCT05951179). Methods: ADVANCED-2 (Cohort B) is a Phase 2, open-label study to evaluate the safety and efficacy of intravesical TARA-002 in BCG-unresponsive adults ≥ 18 years with high-grade NMIBC CIS (± Ta/T1). Key exclusion criteria include penicillin allergy; history of ≥ T2 bladder cancer, nodal, or metastatic disease; or concomitant prostatic or upper tract urothelial involvement. TARA-002 is delivered intravesically for 2 hours and includes induction (6 weekly doses), reinduction (if persistent disease at 3 months), and maintenance (through 24 months). Response is assessed every 3 months for 2 years. Biopsy is mandated at Month 3. Long-term follow-up is conducted up to 60 months. Safety is monitored throughout the study. The primary endpoint is complete response (CR) at any time defined by the absence of any high-grade recurrence. The key secondary endpoint is duration of response. Results: As of 07-October-2025, 32 BCG-unresponsive participants have been enrolled. Majority of participants were White (84.4%, 27 of 32), non-Hispanic (93.8%, 30 of 32), and male (68.8%, 22 of 32). The median age was 74 years (range: 47 to 92). The majority of participants had a baseline diagnosis of CIS only ie, without concomitant Ta/T1 (75.0%, 24 of 32). TARA-002 demonstrated a 68.4% (13 of 19) CR at any time in evaluable participants. The 6-month CR was 75.0% (9 of 12), the 9-month CR was 50.0% (4 of 8), and the 12-month CR was 37.5% (3 of 8). The salvage rate was 75.0% (6 of 8) with reinduction therapy. Most treatment-emergent adverse events (TEAEs) were mild (CTCAE Grades 1-2) and transient; no participants experienced higher than Grade 3 TEAEs. No participants experienced drug-related serious adverse events (SAEs) or drug-related TEAEs leading to withdrawal or death. Conclusions: In participants with BCG-unresponsive high-risk NMIBC with CIS ± Ta/T1, TARA-002 appears to be well tolerated and demonstrated encouraging efficacy, supporting ongoing accrual of the ADVANCED-2 study. Further follow-up will inform durability of response, and data will be updated based on evaluable time points at the time of the presentation. Clinical trial information: NCT05951179 .

496 Background: Approximately 10% of patients with renal cell carcinoma (RCC) have an associated venous tumor thrombus (VTT), the presence of which impacts surgical management and increases perioperative risk. Historical systemic therapy regimens had limited success in downsizing VTT; however, the impact of immune checkpoint inhibitors (ICIs) on VTT shrinkage is unknown. Our primary objective is to assess VTT shrinkage comparing responses to ICI versus non-ICI regimens. Methods: This multicenter retrospective cohort study included patients with RCC and VTT from 2006-2024 who received upfront systemic therapy. Patients were evaluated at tertiary referral centers across Mayo Clinic Rochester, Florida, and Arizona. Systemic therapies were categorized as ICI versus non-ICI regimens. VTT length was quantified by distance relative to the superior border of the renal vein ostium. The primary outcome was change in VTT length on serial imaging as measured by absolute length reduction (cm), RECIST version 1.1 criteria, and Mayo VTT level reclassification. Linear mixed-effect models (LMMs) identified associations with VTT shrinkage and clinicopathologic features. Results: A total of 108 patients with median age 65 years (IQR 57-71) were included, of whom 49 (45%) received ICI regimens. ICI regimens were associated with greater VTT shrinkage (1cm vs 0.1 cm, p=0.025), increased RECIST responses (51% vs 32%, p=0.046), and a higher rate downstaging per Mayo VTT level (33% vs 12%, p=0.008) compared to non-ICI regimens. On multivariable LMM analysis, ICI regimens remained more likely to result in VTT shrinkage compared to non-ICI regimens (-0.12 cm/month, 95% CI –0.24-0.00, p=0.046). Absence of abdominal lymphadenopathy was also associated with VTT shrinkage (-0.18cm/month, 95% CI -0.06- -0.30, p=0.004). Initial Mayo VTT level, IMDC risk, and number of metastatic sites were not associated with VTT shrinkage. Conclusions: Treatment with ICI-regimens resulted in VTT shrinkage and Mayo VTT level reduction. This is a particularly important area of exploration as radical nephrectomy and tumor thrombectomy carry up to a 40% risk of peri-operative major complications. These data support using ICI regimens for patients with RCC with VTT who are not candidates for upfront surgery and prioritizing ICI regimens in neoadjuvant clinical trials.