Gilbert, Scott M.

LBA629 Background: Whether BCG strain influences clinical efficacy is unclear. BCG shortages and a reliance on a single strain may impact disease outcomes. Evidence also suggests that priming with intradermal (ID) BCG vaccination prior to intravesical (IVe) BCG enhances anti-tumor immunity and cancer clearance. Co-primary objectives address these issues. Methods: The trial design calls for 924 eligible patients with BCG naïve non-muscle invasive bladder cancer (NMIBC) (HG Ta/T1 +/- CIS or CIS alone) with negative purified protein derivative (PPD) to be randomized in a 1:1:1 ratio, to IVe TICE (Arm 1), IVe Tokyo-172 (Arm 2), or ID + IVe Tokyo-172 (Arm 3) BCG, stratifying on age group and clinical stage. IVe BCG included 6 weekly instillations (induction) and three weekly instillations (maintenance) at 3 and 6 months (mo), then every 6 mo for 3 years. Objective 1 tests whether Tokyo-172 BCG is non-inferior (NI) to TICE BCG, specifying a NI hazard ratio=1.34 (84% power). Objective 2 tests whether priming with ID prior to IVe Tokyo-172 is superior to IVe Tokyo-172 (HR=0.71, 83% power). The primary endpoint is high-grade recurrence-free survival (HG-RFS) censored at last cystoscopy, using a one-sided α=0.021 for each test. A Cox model adjusting for the stratification factors is used. Secondary endpoints include adverse events, 6-mo biopsy-proven complete response (CR) in patients with CIS +/- Ta, T1, duration of CR, PPD conversion and HG-RFS, progression-free survival (PFS) and quality of life. Max follow-up is 5 years. Results: 1000 (984 eligible) patients were enrolled from 2/17-12/20. Median (IQR) follow up is 4.6 (3.6, 5.0) yrs. Median age (range) is 70 yrs (26, 99), 17% are female, 9% are non-white, and 34% had CIS at entry. HG-RFS, CR, duration of CR at 4 yrs, and PFS were similar among arms (Table). PPD conversion occurred in 29% and was not correlated with HG-RFS. Gr 1-2 AE rate was similar (67%, 71%, and 67%) and Gr 3-4 (no Gr 5s) rate was 6%, 11%, and 14% for Arms 1,2, and 3, respectively. Conclusions: Tokyo-172 is non-inferior to TICE BCG in terms of HG RFS and CIS CR and is similar for PFS. Gr 3-4 AE rate is higher with Tokyo-172. Priming with Tokyo-172 BCG does not improve HG RFS. PPD conversion is not prognostic. Clinical trial information: NCT #03091660 . CIS Component N (eligible) 5-yr HG RFS HG RFSHR (95.8% CI) @ 5-yrPFS PFS HR(95% CI) @ CR %(95% CI) 4 yr CR duration Tice Ive 333 (330) 58% 79% 62%; 71/114(53%, 71%) 80% Tokyo Ive 332 (327) 64% *0.82(0.63, 1.08) 79% *0.99(0.70, 1.39) 60%; 66/110(50%, 69%) 83% Tokyo ID + Ive 335 (327) 63% **1.00(0.76, 1.33) 77% **1.07(0.76, 1.51) 63%; 69/109(54%, 72%) 80% 3 mo. PPD + conversionY vs. N 782 evaluable225 (29%)557 (71%) 69%67% ^HR=0.91(0.68, 1.22) * Tokyo-172 vs. Tice, ** Tokyo Priming vs. Tokyo no priming. ^conversion to PPD + vs. – @ adjusted for 2 strat factors (and arms for PPD model). PFS event = MIBC, metastasis, or death.

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

Objectives To compare survival and oncological outcomes of cisplatin‐ineligible patients (Cis‐I) and cisplatin‐eligible (Cis‐E) patients with muscle‐invasive bladder cancer (MIBC) undergoing immediate radical cystectomy (IRC), as IRC is currently considered the standard‐of‐care for Cis‐I patients with MIBC. Patients and Methods Data from patients with clinical (c)T2–4cN0–1M0 MIBC undergoing IRC, between 2006 and 2021, were retrospectively analysed from four tertiary care centres in the United States. Overall, recurrence‐free and event‐free survival were described using the Kaplan–Meier method and tested using the log‐rank test. For context, we compared survival outcomes against those in Cis‐E patients with MIBC undergoing IRC from the Southwest Oncology Group (SWOG)‐8710 trial. Results Overall, 379 Cis‐I and 125 Cis‐E patients with cT2–4cN0–1M0 MIBC who underwent IRC were included. Cis‐I patients included 44.8% cT3/4 vs 60% cT3/4 in the Cis‐E group. Overall, 83.3% of Cis‐I and 79.2% of Cis‐E patients died during follow‐up. The median event‐free and overall survival were 12.1 and 14.5 months for the Cis‐I group and 28.8 and 60.1 months for the Cis‐E group ( P < 0.001). [Correction added on 10 October 2025, after first online publication: The preceding sentence has been revised in this version.] Limitations include retrospective comparison of contemporary multi‐institutional data with that of a randomised control trial. Conclusions The Cis‐I patients with MIBC undergoing IRC fared poorly, with a median overall survival of 14.5 (95% confidence interval 11.1–17.9) months, mostly due to non‐cancer‐related deaths. These results provide a benchmark for clinical trials exploring novel agents or alternative chemotherapy regimens in Cis‐I patients with MIBC.

Abstract Objectives There is limited research on suicide risk screening (SRS) among head and neck cancer (HNC) patients, a population at increased risk for suicide. To address this gap, this single-site mixed methods study assessed oncology professionals' perspectives about the feasibility, acceptability, and appropriateness of an electronic SRS program that was implemented as a part of routine care for HNC patients. Methods Staff who assisted with SRS implementation completed (e.g., nurses, medical assistants, advanced practice providers, physicians, social workers) a one-time survey (N = 29) and interview (N = 25). Quantitative outcomes were assessed using previously validated feasibility, acceptability, and appropriateness measures. Additional qualitative data were collected to provide context for interpreting the scores. Results Nurses and medical assistants, who were directly responsible for implementing SRS, reported low feasibility, acceptability, and appropriateness, compared with other team members (e.g., physicians, social workers, advanced practice providers). Team members identified potential improvements needed to optimize SRS, such as hiring additional staff, improving staff training, providing different modalities for screening completion among individuals with disabilities, and revising the patient-reported outcomes to improve suicide risk prediction. Conclusion Staff perspectives about implementing SRS as a part of routine cancer care for HNC patients varied widely. Before screening can be implemented on a larger scale for HNC and other cancer patients, additional implementation strategies may be needed that optimize workflow and reduce staff burden, such as staff training, multiple modalities for completion, and refined tools for identifying which patients are at greatest risk for suicide.