Roundup

DURVALUMAB IN COMBINATION WITH BACILLUS CALMETTE–GUERIN FOR BACILLUS CALMETTE–GUERIN-NAIVE, HIGH-RISK, NONMUSCLE-INVASIVE BLADDER CANCER (POTOMAC): FINAL ANALYSIS OF A RANDOMIZED, OPEN-LABEL, PHASE 3 TRIAL This randomized, open-label, phase 3 trial enrolled patients aged >18 years with Bacillus Calmette–Guerin (BCG)-naive, high-risk nonmuscle-invasive bladder cancer (NMIBC).[1] Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months) (n = 339), durvalumab plus BCG induction only (n = 336), or BCG induction and maintenance (comparison group) (n = 337). From June 2018 to October 2020, 53%, 71%, and 54% completed treatment. At a median follow-up of 60.7 months (interquartile range [IQR] 51.5–66.5), there were 20% disease-free survival (DFS) events in the durvalumab plus BCG induction and maintenance group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death versus the comparison group (hazard ratio 0·68 [95% confidence interval 0·50–0·93]; log-rank P = 0·015). These results support the use of durvalumab in combination with BCG induction and maintenance therapy for 1 year as a potential new treatment for this patient population. BACKGROUND AND UPDATE FOR ECOG-ACRIN EA8212: A RANDOMIZED PHASE 3 TRIAL OF INTRAVESICAL BACILLUS CALMETTE–GUÉRIN VERSUS INTRAVESICAL DOCETAXEL AND GEMCITABINE TREATMENT IN BACILLUS CALMETTE-GUERIN-NAÏVE HIGH-GRADE NONMUSCLE-INVASIVE BLADDER CANCER BCG is currently recommended as adjuvant therapy for high-risk NMIBC. In response to the BCG shortage, gemcitabine plus docetaxel (Gem/Doce) has been utilized. However, data on Gem/Doce are limited to retrospective and single-center studies. ECOG-ACRIN EA8212 is an ongoing phase 3 randomized trial.[2] Eligible patients include adults aged >18 years with BCG-naive high-grade NMIBC (HG Ta, carcinoma in situ [CIS], or HG T1). Exclusion criteria include the presence of sarcomatoid, plasmacytoid, micropapillary, or neuroendocrine variant histology, as well as prior intravesical chemotherapy. Patients (n = 870) randomized to arm A received intravesical gemcitabine (1 g/50 ml normal saline [NS]) and docetaxel (40 mg/50 ml NS) weekly for 6 weeks, with monthly maintenance for 2 years. Patients randomized to arm B received intravesical BCG with a standard 6-week induction course followed by 3-week maintenance courses at 3, 6, 12, 18, 24, 30, and 36 months. The primary objective was to assess whether event-free survival for GemDoce is noninferior to that with standard BCG for patients with BCG-naïve high-grade NMIBC. The secondary objective was to compare changes in cancer-specific and bladder cancer-specific quality of life. Other secondary objectives include assessing safety and toxicity, as well as determining cystectomy-free and progression-free survival. The trial is being run through the National Clinical Trials Network. The first patient was enrolled on February 7, 2023. GEMCITABINE INTRAVESICAL SYSTEM PLUS CETRELIMAB OR CETRELIMAB ALONE AS NEOADJUVANT THERAPY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER: PRIMARY ANALYSIS AND BIOMARKER RESULTS OF SUNRISE-4 TRIAL 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 (NCT04919512) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200) plus cetrelimab or cetrelimab monotherapy in patients with MIBC.[3] Adults with ECOG performance status 0-1, cT2-T4a N0M0, ineligible/refusing NAC, and planned for RC were randomized 5:3 to receive TAR-200 plus cetrelimab (Cohort 1 [C1]) or cetrelimab monotherapy (C2). The primary endpoint was pathologic complete response (pCR) at RC. pCR, pathological overall response (pOR), and 1-year recurrence-free survival (RFS) rates were 38%, 53%, and 77%, respectively, in C1 and 28%, 44%, and 64% in C2. TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rate compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. PROLONGED PROGRESSION-FREE SURVIVAL, DISEASE-FREE SURVIVAL, AND CYSTECTOMY AVOIDANCE WITH INTERLEUKIN-15 RECEPTOR LYMPHOCYTE-STIMULATING AGENT NOGAPENDEKIN ALFA INBAKICEPT PLUS BACILLUS CALMETTE-GUÉRIN IN BACILLUS CALMETTE–GUÉRIN-UNRESPONSIVE PAPILLARY-ONLY NONMUSCLE-INVASIVE BLADDER CANCER The QUILT-3.032 multicenter study, conducted during July 2017–2024, evaluated intravesical nogapendekin alfa inbakicept (NAI), an interleukin-15 receptor superagonist, combined with BCG in patients with papillary-only, BCG-unresponsive high-grade NMIBC.[4] Eighty patients received weekly induction with 400 mg NAI + 50 mg BCG intravesically weekly for 6 consecutive weeks. NAI enhances NK (natural killer) and CD8+ T-cell activation without stimulating regulatory T cells, thereby restoring BCG-induced trained immunity. The 12-month DFS was 58.2%, with a median DFS of 25.3 months. Progression-free survival remained high (94.9% at 12 months and 83.1% at 36 months). Cystectomy avoidance was notable, with 92.2% remaining cystectomy-free at 12 months and 81.8% at 36 months. Disease-specific survival exceeded 96% at 36 months, and overall survival was 91.7% at 36 months. Adverse events were mostly mild, comparable to those observed with BCG alone. The therapy demonstrated durable bladder-sparing efficacy with excellent tolerability, representing a significant advancement for BCG-unresponsive papillary NMIBC, where treatment options are limited. IRREVERSIBLE ELECTROPORATION FOR PROSTATE TISSUE ABLATION IN PATIENTS WITH INTERMEDIATE-RISK PROSTATE CANCER: RESULTS FROM THE PRESERVE TRIAL The PRESERVE trial evaluated irreversible electroporation using the NanoKnife System for prostate tissue ablation in men with intermediate-risk prostate cancer.[5] This prospective, single-arm pivotal study enrolled 121 treated patients and measured effectiveness by the proportion of patients achieving a negative in-field biopsy at 12 months, along with safety based on adverse event incidence and severity. At the 12-month evaluation, the negative in-field biopsy rate was reported as 71% with a median PSA reduction of 68.2% at 6 months and a median PSA nadir reached at 3.5 months. Urinary outcomes showed a mean 12-month change of 3 on the UCLA-EPIC urinary scores, and 84% of patients with good baseline sexual function maintained erections sufficient for penetration. Grade 3 adverse events occurred in 12% of patients, including three events attributed to the procedure. The study concluded that irreversible electroporation with NanoKnife is safe and effective for prostate tissue ablation with favorable oncological and functional results. DEVELOPMENT AND VALIDATION OF A NOVEL PLASMA METABOLOMIC SIGNATURE FOR THE DETECTION OF RENAL CELL CARCINOMA This multicenter study aimed to address a significant issue in renal cancer care: the lack of a simple blood test that can reliably detect renal cell carcinoma (RCC) at an early stage.[6] Researchers analyzed blood samples from more than 1600 people across five hospitals and discovered seven metabolic molecules in the blood that consistently changed in patients with RCC. Using these markers, they developed an artificial intelligence (AI)-based tool called RCC AI Detector (RCAID), which can distinguish between cancer patients and healthy individuals with very high accuracy. Notably, the test performed impressively not only for early cancers but also for advanced and nonclear cell types. The team then explored tumor tissues and found that the same metabolic pathways were disrupted within the cancer, providing insight into why these markers appear in the blood. They also identified reduced activity of a key regulator, HNF1B, which may drive these metabolic changes. Overall, this research presents a promising, minimally invasive blood test for earlier and more accurate detection of RCC. EFFICACY OF DRUG-COATED BALLOON DILATION VERSUS ENDOSCOPIC STANDARD TREATMENT IN POSTERIOR URETHRAL STENOSIS: A REAL-WORLD COMPARATIVE STUDY This study compared Optilume® drug-coated balloon (DCB) dilation with standard transurethral endoscopic treatment for posterior urethral stenosis, including vesicourethral anastomotic stenosis and bladder neck contracture.[7] A total of 141 patients were analyzed – 65 received DCB and 76 underwent standard treatment. Baseline characteristics, prior treatments, and radiotherapy exposure were comparable. RFS was significantly better with Optilume, with fewer restenosis events at 15 months. Multivariate analysis confirmed DCB as an independent protective factor (HR 0.40). Functional outcomes in the DCB group showed marked improvements, with median Qmax increasing from 9 to 22 mL/s and postvoid residual reducing from 55 mL to 0 mL. No major perioperative complications occurred, and continence was preserved. Authors conclude that Optilume is a promising, minimally invasive, and safe alternative for posterior urethral stenosis, although larger studies with longer follow-up are needed for durability assessment. SHORT-TERM OUTCOMES FOLLOWING TRANSURETHRAL DORSAL BUCCAL GRAFT URETHROPLASTY FOR FEMALE URETHRAL STRICTURES This study presents 12-month clinical and patient-reported outcomes following a novel transurethral approach to dorsal inlay buccal graft urethroplasty.[8] From October 2021 to November 2024, 21 females underwent surgery. The preoperative evaluation included cystoscopy, uroflowmetry, and/or a voiding cystourethrogram. Follow-up cystoscopy, uroflowmetry, and patient-reported outcomes were assessed using the global response assessment. Success was defined as the absence of recurrence on cystourethroscopy. Ninety-five percent had undergone prior treatments (90% dilation/internal urethrotomy and 9% urethroplasty). Stricture locations varied across the distal (33%), mid (19%), proximal (19%), and multifocal/panurethral (19%) regions. The median operative duration was 60 min (IQR: 56–86 min), and all patients were discharged on the day of surgery. Nineteen patients (90%) underwent a dorsal inlay procedure, whereas two (10%) required a combined dorsal and ventral inlay due to obliterative stricture. No complications were observed. The median follow-up was 13.2 months (IQR: 5.1–23.5), during which time one patient underwent retreatment for recurrent stricture. Clinical success was 95% at 4 months and 92% at 12 months. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.