Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Mechanism of action of nadofaragene firadenovec-vncg.

Effective bladder-preserving therapeutic options are needed for patients with bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg (Adstiladrin®) was approved by the US Food and Drug Administration as the first gene therapy in urology and the first intravesical gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. The proposed mechanism of action underlying nadofaragene firadenovec efficacy is likely due to the pleiotropic nature of interferon-α and its direct and indirect antitumor activities. Direct activities include cell death and the mediation of an antiangiogenic effect, and indirect activities are those initiated through immunomodulation of the innate and adaptive immune responses. The sustained expression of interferon-α that results from this treatment modality contributes to a durable response. This review provides insight into potential mechanisms of action underlying nadofaragene firadenovec efficacy.

Dissemination of Circulating Tumor Cells in Breast and Prostate Cancer: Implications for Early Detection.

Burgeoning evidence suggests that circulating tumor cells (CTCs) may disseminate into blood vessels at an early stage, seeding metastases in various cancers such as breast and prostate cancer. Simultaneously, the early-stage CTCs that settle in metastatic sites [termed disseminated tumor cells (DTCs)] can enter dormancy, marking a potential source of late recurrence and therapy resistance. Thus, the presence of these early CTCs poses risks to patients but also holds potential benefits for early detection and treatment and opportunities for possibly curative interventions. This review delves into the role of early DTCs in driving latent metastasis within breast and prostate cancer, emphasizing the importance of early CTC detection in these diseases. We further explore the correlation between early CTC detection and poor prognoses, which contribute significantly to increased cancer mortality. Consequently, the detection of CTCs at an early stage emerges as a critical imperative for enhancing clinical diagnostics and allowing for early interventions.

Factors associated with the Journal Impact Factor (JIF) for Urology and Nephrology Journals

Purpose: The Journal Impact Factor (JIF) is an index used to compare a journal's quality among academic journals and it is commonly used as a proxy for journal quality. We sought to examine the JIF in order to elucidate the main predictors of the index while generating awareness among scientific community regarding need to modify the index calculation in the attempt to turn it more accurate. Materials and Methods: Under the Urology and Nephrology category in the Journal Citations Report Website, the top 17 Journals by JIF in 2011 were chosen for the study. All manuscripts’ abstracts published from 2009-2010 were reviewed; each article was categorized based on its research design (Retrospective, Review, etc). T and correlation tests were performed for categorical and continuous variables respectively. The JIF was the dependent variable. All variables were then included in a multivariate model. Results: 23,012 articles from seventeen journals were evaluated with a median of 1,048 (range=78-6,342) articles per journal. Journals with a society affiliation were associated with a higher JIF (p=0.05). Self-citations (rho=0.57, p=0.02), citations for citable articles (rho=0.73, p=0.001), citations to non-citable articles (rho=0.65, p=0.0046), and retrospective studies (rho=-0.51, p=0.03) showed a strong correlation. Slight modifications to include the non-citable articles in the denominator yield drastic changes in the JIF and the ranking of the journals. Conclusion: The JIF appears to be closely associated with the number of citable articles published. A change in the formula for calculating JIF to include all types of published articles in the denominator would result in a more accurate representation.

Complications rates of non-oncologic urologic procedures in population-based data: a comparison to published series

PUSPOSE: Published single institutional case series are often performed by one or more surgeons with considerable expertise in specific procedures. The reported incidence of complications in these series may not accurately reflect community-based practice. We sought to compare complication and mortality rates following urologic procedures derived from population-based data to those of published single-institutional case series. MATERIALS AND METHODS: In-hospital mortality and complications of common urologic procedures (percutaneous nephrostomy, ureteropelvic junction obstruction repair, ureteroneocystostomy, urethral repair, artificial urethral sphincter implantation, urethral suspension, transurethral resection of the prostate, and penile prosthesis implantation) reported in the U.S.’s National Inpatient Sample of the Healthcare Cost and Utilization Project were identified. Rates were then compared to those of published single-institution series using statistical analysis. RESULTS: For 7 of the 8 procedures examined, there was no significant difference in rates of complication or mortality between published studies and our population-based data. However, for percutaneous nephrostomy, two published single-center series had significantly lower mortality rates (p < 0.001). The overall rate of complications in the population-based data was higher than published single or select multi-institutional data for percutaneous nephrostomy performed for urinary obstruction (p < 0.001). CONCLUSIONS: If one assumes that administrative data does not suffer from under reporting of complications then for some common urological procedures, complication rates between population-based data and published case series seem comparable. Endorsement of mandatory collection of clinical outcomes is likely the best way to appropriately counsel patients about the risks of these common urologic procedures.

Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

Purpose: In this study, we investigated the ability of UroVysion™ to assess response to intravesical therapy in patients with high risk superficial bladder tumors. Materials and methods: We performed a retrospective review of patients undergoing intravesical therapy for high risk superficial bladder tumors. Urine specimens were collected for UroVysion™ analysis before and immediately after a course of intravesical therapy. Cytology and cystoscopy were performed six weeks after treatment, using either a positive cytology or visible abnormality on cystoscopy as a prompt for biopsy. The operating characteristics of the UroVysion™ test were then determined. Results: 41 patients were identified in whom 47 cycles of induction and 41 cycles of maintenance intravesical therapy were given during the study period. This yielded a total of 88 treatment and evaluation cycles. Median follow-up was 9 months per induction (range 1-21 months) and 13 months per patient (range 1-25 months). A total of 133 urine samples were collected for UroVysion™ of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysion™ testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85 percent, 61 percent, and 71 percent. Conclusions: The use of UroVysion™ following intravesical therapy for high-risk superficial bladder tumors helps to identify patients at high risk of refractory or recurrent disease who should undergo immediate biopsy under anesthesia.