Background: Despite extensive research to identify biomarkers of response in patients with non–muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.Methods: Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed.Results: Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14–0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16–3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01–1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07–1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91–0.99; P = 0.04) at week 13 from baseline best predicted time to event.Conclusions: Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC.Impact: This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.

Recently, three prospective randomized trials have shown that adjuvant radiotherapy (ART) after radical prostatectomy for the patients with pT3 and/or positive margins improves biochemical progression-free survival and local recurrence free survival. But, the optimal management of these patients after radical prostatectomy is an issue which has been debated continuously. The object of this study was to determine the necessity of adjuvant radiotherapy (ART) by reviewing the outcomes of observation without ART after radical prostatectomy (RP) in patients with pathologic indications for ART according to the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline. From a prospectively maintained database, 163 patients were eligible for inclusion in this study. These men had a pathological stage pT2–3 N0 with undetectable PSA level after RP and met one or more of the three following risk factors: capsular perforation, positive surgical margins, or seminal vesicle invasion. We excluded the patients who had received neoadjuvant hormonal therapy or adjuvant treatment, or had less than 24 months of follow-up. To determine the factors that influenced biochemical recurrence-free (BCR), univariate and multivariate Cox proportional hazards analyses were performed. Among the 163 patients, median follow-up was 50.5 months (24.0-88.2 months). Of those men under observation, 27 patients had BCR and received salvage radiotherapy (SRT). The multivariate Cox analysis showed that BCR was marginally associated with pre-operative serum PSA (P = 0.082), and the pathologic GS (HR, 4.063; P = 0.001) was an independent predictor of BCR. More importantly, in 87 patients with pre-operative PSA < 6.35 ng/ml and GS ≤ 7, only 3 developed BCR. Of the 163 patients who qualified for ART based on the current AUA/ASTRO guideline, only 27 (16.6%) developed BCR and received SRT. Therefore, using ART following RP using the current recommendation may be an overtreatment in an overwhelming majority of the patients.

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.

PURPOSE: Molecular characterization of anatomically distinct urothelial carcinoma in the upper tract (UTUC) and bladder (UCB) has been challenging because of the rarity of UTUC. However, recent advances in real-world data curation have facilitated the generation of larger UTUC cohorts. In this study, we investigated the somatic, germline, and immunologic landscapes of UTUC compared with UCB. METHODS: From the Tempus Database, we retrospectively analyzed 505 UTUC and 2,416 UCB cases. Tumors were sequenced using Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration, tumor mutational burden (TMB), PD-L1, microsatellite instability (MSI), and mismatch repair (MMR) were evaluated. Potential germline alterations were assessed in 46 genes for patients with tumor/normal matched sequencing (UTUC, n = 285; UCB, n = 1,359). RESULTS: Alterations in TERT, TP53, RB1, ERBB2, and CDKN1A were more frequent in UCB, whereas KMT2D, FGFR3, CDKN2B, KRAS , and MYC were more frequent in UTUC. Germline variants were found in 4.8% of UCB and 5.6% of UTUC, with trends toward higher Lynch syndrome–associated gene alterations ( MLH1, MSH2, MSH6, PMS2 ) in UTUC (0.6% v 1.8%, P = .059). The prevalence of TMB ≥10 mut/Mb was higher in UCB (17% v 11%, P < .001). UCB had higher PD-L1 positivity ( P = .013), whereas UTUC had more MSI-high (UTUC = 3.2% v UCB = 1%, P = .001) and MMR-deficient ( P = .020) cases. CD4 ⁺ and regulatory T-cell infiltrates were similar in both. CONCLUSION: By comprehensive molecular characterization of UC, we observed distinct genomic alterations and tumor microenvironment patterns in UTUC and UCB. Further research is warranted to elucidate the clinical implications of these findings. We compared the genetic and immune features of upper tract and bladder cancers. Our study found key differences that could affect treatment decisions, such as specific gene changes and immune markers. These insights may help doctors personalize therapies and improve patient care.