IP36-06 ASSOCIATION OF GENOMIC DISEASE BURDEN MARKERS AND PROGRAMMED DEATH-LIGAND 1 WITH CLINICAL OUTCOMES IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER TREATED WITH GEMCITABINE INTRAVESICAL SYSTEM + CETRELIMAB (CET) OR CET ALONE IN THE PHASE 2 SUNRISE-4 TRIAL

The Journal of Urology · 2026-04-27

IP35-23 ARE TURBT PATHOLOGY OVERREADS NECESSARY? A DESCRIPTIVE REVIEW OF PATHOLOGIC CONCORDANCE FOR REFERRED BLADDER CANCER PATIENTS OVER A 12-YEAR PERIOD

The Journal of Urology · 2026-04-27

Neoadjuvant (Neoadj) gemcitabine intravesical system (Gem-iDRS) plus cetrelimab (CET) or CET alone in patients (pts) with muscle-invasive bladder cancer (MIBC) ineligible for/refusing neoadj cisplatin-based chemotherapy (NAC): Updated perioperative outcomes from SunRISe-4.

Journal of Clinical Oncology · 2026-03-01

748 Background: There is a high unmet need for effective neoadj treatments (tx) for MIBC that maintain overall health and do not delay or complicate planned radical cystectomy (RC). Gem-iDRS, previously TAR-200, is a novel intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. SunRISe-4 (NCT04919512) is a randomized phase 2 study evaluating neoadj Gem-iDRS and CET in pts with MIBC who are ineligible for or refuse NAC. This analysis from SunRISe-4 evaluated if neoadj Gem-iDRS plus CET (Cohort 1 [C1]) or CET alone (C2) impacted pre- and post-RC surgical, laboratory, or safety outcomes, including clinical declines, delay to RC, or increased perioperative complications. Methods: Pts (≥18 yr; ECOG PS 0-1) had histologically confirmed cT2-T4a N0M0 MIBC, were ineligible for or refused NAC, and planned for RC. Pts were randomized 5:3 to receive Gem-iDRS plus CET or CET alone Q3W for 12 wks, followed by RC (protocol-specified RC window: 11-15 wks). Perioperative outcomes included time to RC, 30- and 90-d post-RC morbidity and mortality, and changes on tx in ECOG PS, BMI, albumin, creatinine, and hemoglobin. ECOG PS was recorded on site at baseline and wks 6 and 36. Results: As of the May 9, 2025, data cutoff, 134 pts underwent RC (C1: 88; C2: 46). Median time to RC was 13.6 wks in C1 and 13.3 wks in C2. Most pts had RC within the window (C1: 85.2%; C2: 84.8%). 5/88 (5.7%) pts in C1 and 6/46 (13.0%) in C2 underwent RC after 15 wks (1 pt had a delay due to grade 2 hematuria,1%, during neoadj tx). 79.3% of C1 and 69.6% of C2 pts received ileal conduit. No clinically significant changes in ECOG, BMI, albumin, creatinine, and hemoglobin were noted on tx. At 30 and 90 d post RC, no significant increase in morbidity or mortality was observed (Table). Conclusions: In pts with MIBC ineligible for or refused NAC, neoadj Gem-iDRS plus CET and CET alone were not associated with declines in overall health, delays to RC, or significant increase in 30- and 90-d post-RC morbidity or mortality. Addition of Gem-iDRS to the checkpoint inhibitor CET did not worsen safety and post-RC morbidity compared with CET alone. Clinical trial information: NCT04919512 . Safety outcomes within 30 and 90 d post RC. Pts, n (%) ≤30 d post RC ≤90 d post RC Overall(N=118) Gem-iDRS + CET (n=76) CET alone (n=42) Overall (N=100) Gem-iDRS + CET (n=68) CET alone (n=32) Morbidity Serious AEs 46 (39.0) 32 (42.1) 14 (33.3) 49 (49.0) 37 (54.4) 12 (37.5) Grade ≥3 AEs 54 (45.8) 38 (50.0) 16 (38.1) 55 (55.0) 40 (58.8) 15 (46.9) Mortality a Any cause 3 (2.5) 1 (1.3) b 2 (4.8) c 4 (4.0) 2 (2.9) d 2 (6.3) c AE, adverse event. a No deaths that occurred ≤30 and 90 d post RC were related to neoadj tx with Gem-iDRS or CET. b Due to hypoxia. c Due to peritonitis and cardiac arrest in 1 pt each. d Due to hypoxia and cardio-respiratory arrest in 1 pt each.

SWOG S1602: A phase III randomized trial to evaluate BCG strain differences and priming with intradermal BCG before intravesical therapy for BCG-naïve high-grade non-muscle invasive bladder cancer (NCT #03091660).

Journal of Clinical Oncology · 2026-03-01

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.

<i>PARP1</i> and <i>BRCA1/2</i> expression and overall survival in high risk of recurrence localized clear cell-type renal cell carcinoma.

Journal of Clinical Oncology · 2026-03-01

514 Background: Poly(ADP-ribose) polymerase 1 (PARP1) senses single strand DNA damage and catalyzes repair mechanisms. PARP inhibitor (PARPi) suppresses PARP1 activity and promotes cell death in BRCA1 or BRCA2 mutated cancers that are homologous recombination repair deficient (HRD) via a phenomenon known as “synthetic lethality”. Utility of PARPi in HRD-negative (HRDn) cancers remain uncertain, although in a preclinical study overexpression—but not endogenous levels—of BRCA2 in mouse hybridoma cells led to HRD and increased sensitivity to DNA crosslinking agents, suggesting potential sensitization to PARPi. In renal cell carcinoma (RCC), HRD mutations are rare and the role of PARPi remains investigational. In this study, PARP1 and BRCA1/2 expression and overall survival (OS) in high risk of recurrence localized clear cell-type renal carcinoma (hrr-ccRCC) were explored. Methods: Batch-corrected bulk mRNA profile (RNA Seq V2 RSEM) and clinical data of HRDn stages II grade 4-only (n = 4) and III (n = 100) ccRCC from The Cancer Genome Atlas Pan-Cancer project were reviewed. Gene expression was classified “high” if mRNA level is higher than median, otherwise it was classified “low”. Survival analyses were Log-rank Kaplan-Meier. Group comparisons were two-tailed Mann-Whitney test. Results: In HRDn hrr-ccRCC (n = 104), BRCA1 and BRCA2 were upregulated by median fold change (mFC) of 1.6 and 3.7, respectively, whereas PARP1 was downregulated by mFC 0.8 compared to normal control (n = 72, all p &lt; 0.0001). BRCA1 and BRCA2 levels were positively correlated (R 2 = 0.71). Median duration of follow-up for OS was 36.5 months (IQR 20.9-60.0). High BRCA2 (n = 54) was associated with superior OS compared to low BRCA2 (n = 50) with hazard ratio (HR) for death at 0.34 (95% CI 0.19-0.63, p = 0.0008). When high BRCA2 group was further stratified by PARP1 level, those with concomitant low PARP1 (n = 16) trended towards a superior OS compared to those with high PARP1 (n = 38) with HR 0.19 (95% CI 0.06-0.60, p = 0.067). Similarly, high BRCA1 (n = 53) was associated with superior OS compared to low BRCA1 (n = 51) with HR 0.53 (95% CI 0.29-0.96, p = 0.04). However, no differential OS was seen when high BRCA1 group was stratified by PARP1 level. No differential OS was seen when low BRCA1 or low BRCA2 groups were stratified by PARP1 level. Conclusions: In this retrospective analysis of HRDn hrr-ccRCC, high BRCA2 was associated with superior OS which was more pronounced with concomitant low PARP1 . High BRCA1 was also associated with superior OS, but PARP1 levels had no influence. The findings of this study may imply a potential therapeutic value of PARP1 suppression with PARPi by mimicking low PARP1 expression in treating HRDn hrr-ccRCC with BRCA2 overexpression. Further investigation is warranted.

Patient awareness and perspectives regarding the value of focal therapy for localized prostate cancer: A cross-sectional study

Urologic Oncology Seminars and Original Investigations · 2026-02-07

Development of a Prognostic Prediction Model for Clinically Significant Prostate Cancer Based on Lesion Zone and Apparent Diffusion Coefficient Value Quantification

Urology · 2026-01-28

TAR-200 plus cetrelimab versus cetrelimab monotherapy as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or decline neoadjuvant cisplatin-based chemotherapy (SunRISe-4): interim analysis of a randomised, open-label phase 2 trial

The Lancet Oncology · 2025-08-27 · 8 citations

Gemcitabine Intravesical System Plus Cetrelimab or Cetrelimab Alone as Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: SunRISe-4 Primary Analysis and Biomarker Results

Journal of Clinical Oncology · 2025-12-03 · 5 citations

PURPOSE Standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC). However, many patients are ineligible for or refuse cisplatin. SunRISe-4 (ClinicalTrials.gov identifier: NCT04919512 ) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200/gem-iDRS) plus cetrelimab or cetrelimab monotherapy in patients with MIBC. METHODS Adults with Eastern Cooperative Oncology Group performance status 0-1, cT2-T4a N0M0, ineligible/refusing NAC, and planned for RC were randomly assigned 5:3, stratified by transurethral resection of bladder tumor completeness (residual tumor ≤3 cm permitted) and T stage, to receive TAR-200 plus cetrelimab (cohort 1) or cetrelimab monotherapy (cohort 2). The primary end point was pathologic complete response (pCR) at RC. Secondary end points included recurrence-free survival (RFS) and safety. Exploratory end points included pathologic overall response (pOR; ≤ypT1N0) and circulating tumor (ct) and urinary tumor (ut) DNA molecular residual disease (MRD). Side-by-side descriptive efficacy summary was planned. RESULTS At the May 9, 2025, data cutoff, 159 patients were treated; 88 in cohort 1 and 46 in cohort 2 underwent RC. pCR, pOR, and 1-year RFS rates were 38%, 53%, and 77% in cohort 1 and 28%, 44%, and 64% in cohort 2, respectively. pCR rates were consistent across subgroups. No new safety signals were observed. Across cohorts, utDNA– status before RC (week 12) and utDNA clearance correlated with pCR ( P &lt; 10 –5 and &lt; 10 –3 , respectively). ctDNA– status at baseline and week 12 was associated with longer RFS compared with ctDNA+ status at the same time point ( P = .04 and 0.01, respectively). CONCLUSION TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rates compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. utDNA and ctDNA MRD results support further investigation as biomarkers for residual local and nonlocal disease, respectively.

INCIDENCE AND PATHOLOGIC OUTCOMES OF CYSTECTOMY IN PATIENTS WITH BACILLUS CALMETTE-GUÉRIN-UNRESPONSIVE NON–MUSCLE-INVASIVE BLADDER CANCER WITH CARCINOMA IN SITU FOLLOWING TREATMENT WITH NADOFARAGENE FIRADENOVEC-VNCG

Urologic Oncology Seminars and Original Investigations · 2025-02-27