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After several decades of therapeutic stagnation, the treatment of patients with urothelial carcinoma has met a revolutionary wave, anticipated by the advent of immune-checkpoint inhibitors (ICI) and followed by newer therapeutic options in the post-ICI setting. These achievements were made in a very short time-frame, thus making the treatment of this disease particularly susceptible to geographical health disparity due to the differences in healthcare systems and approval processes of the regulatory authorities. Furthermore, additional barriers to access innovative care are represented by a limited coverage of clinical trials availability, that is consistent in focusing on selected geographical areas, across trials and clinical settings. Here, we present the current picture of new drug approvals in urothelial carcinoma worldwide, and we also focus our considerations onto the spectrum of ongoing trial inclusion possibilities, trying to understand what are the current gaps in clinical research and routine practice, identifying a way to move forward., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Urothelial cancer care is particularly susceptible to geographical health disparity given its complex nature, requiring access to several specialists such as a urologist, a medical oncologist, a radiation oncologist, a surgical oncologist, and multidisciplinary care teams. Furthermore, other barriers to care access in underserved areas include travel burden, longer wait times, late-stage disease at the time of diagnosis, cost, type of treatment, less enrollment in clinical trials, lack of follow-up among cancer survivors, and less research funding in this area. Here, we discuss the impact of geographical location on access to urothelial cancer care, management decisions, and outcomes and we reflect on how to address geographical disparities in care delivery.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Benign external compression of the Inferior Vena Cava (IVC) with distal thrombus formation is seldomly described in the medical literature., Case Presentations: We report a case of external IVC compression by a dilated right renal pelvis and hydronephrotic kidney secondary to longstanding Ureteropelvic Junction (UPJ) obstruction found in a 68-year-old male. Management included therapeutic anticoagulation, IVC filter placement, attempted thrombectomy by interventional radiology, and interval repeats imaging. This patient demonstrated complete resolution of the caval thrombus on repeat imaging 2 months following discharge. This case highlights the importance of interdisciplinary team coordination, a crucial component of patient's management and eventual treatment plan. It is reasonable to manage patients with IVC thrombus with anticoagulation alone., Conclusion: In the modern era, angiointerventional techniques provide minimally invasive approaches to the management of vascular disorders and minimize morbidity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer., Methods: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 10 11 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849., Findings: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths., Interpretation: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state., Funding: FKD Therapies Oy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Urogenital fistulas in the setting of foreign body are rare. Isolated vesicovaginal fistula is the most common and has been reported in the setting of retained intraureterine device, 1 , 2 neglected pessary 3 , 4 and atypical insertions related mostly to sexual activity or underlying psychiatric disorders. 5-7 Combined vesicovaginal and ureterovaginal fistulas related to foreign body are extremely rare. To our knowledge, we present the first reported case of bilateral ureterovaginal fistula and concurrent vesicovaginal fistula in the setting of retained pessary., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1-T4, N0-N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017., (© 2014 The Authors. BJU International © 2014 BJU International.)

The acquisition process for infant and toddler polysomnography requires pediatric-specific equipment and specially trained personnel. Pediatric laboratories must keep in mind the importance of including the parent through-out the process. The demand for infant and pediatric polysomnography continues to grow as new research increasingly demonstrates the value of studying physiologic variables collected during the study.

Background: Being partnered confers significant benefits in survival for patients with prostate cancer, yet little is known of the impact of relationship status on health-related quality of life (HRQOL). The authors evaluated the influence of partnership on measures of HRQOL., Methods: The authors studied 291 patients who were enrolled in a program that provided free treatment to impoverished, uninsured men with prostate cancer. The associations between relationship status and measures of general and disease-specific HRQOL were evaluated. Results from multivariate models determined the independent effect of partnership on HRQOL., Results: Partnered patients were more likely than unpartnered patients to be Hispanic (58% vs. 34%) and were more likely to have elected surgical therapy (49% vs. 34%). Multivariate analyses, controlling for age, ethnicity, disease stage, and treatment type, revealed that partnered patients had better mental health (P = 0.009), less urinary bother (P = 0.011), higher spirituality (P = 0.037), and lower symptom distress (P = 0.005) than unpartnered participants., Conclusions: Relationship status had a positive effect on the quality of life of low-income, uninsured men with prostate cancer.

Purpose: We evaluated mental health outcomes in a cohort of low income, uninsured men with prostate cancer and identified factors that influence mental health., Materials and Methods: We performed a retrospective cohort study of 277 subjects enrolled in a program that provides free care to men with prostate cancer who have an annual income of no more than 200% of the federal poverty level. We compared scores on the 5-item RAND Mental Health Inventory (MHI-5) to those in individuals with other chronic diseases. We also examined the relationship between MHI-5 scores and validated measures of general and disease specific health related quality of life. Disease specific quality of life included measures of distress related to urinary, sexual and bowel habits. Multivariate analyses were performed to evaluate factors associated with mental health score., Results: Most men studied were Hispanic (51.6%) and had at most a high school education (85.9%). Mean MHI-5 score +/- SD was 68 +/- 23 on a 100-point scale, significantly worse than cohorts of men with diabetes, congestive heart failure and chronic pulmonary disease. Hispanic ethnicity, urinary bother and bowel bother were negatively associated with mental health. Spirituality and physical functioning were positively associated with mental health., Conclusions: Economically disadvantaged men with prostate cancer report worse mental health than people with other chronic diseases. Patients especially at risk are those with significant urinary or bowel distress, poor physical health, low spirituality and Hispanic ethnicity.

Objectives: To describe the confidence of low-income patients with prostate cancer in interacting with physicians. Men with prostate cancer need to communicate easily with their physicians when facing treatment decisions and symptom management; however, little is known about whether low-income men are confident in these interactions., Methods: We used validated instruments to measure self-efficacy in patient-physician interactions, emotional well-being, symptom distress, satisfaction with care, and health-related quality of life among low-income men receiving prostate cancer treatment through a statewide public assistance program. We abstracted clinical variables from medical records. We dichotomized self-efficacy scores empirically on the basis of the sample distribution and conducted univariate and multivariate analyses., Results: The self-efficacy scores were skewed toward the high scores, with 77% in the high range. Those (23%) with low self-efficacy were more likely to have poor emotional well-being, symptom distress, role limitations--emotional, low social function, and poor urinary, sexual, and bowel outcomes. In multivariate analysis, low-income men were more likely to have low self-efficacy if they were less satisfied with their care, did not have confidence in their provider, or had more symptom distress., Conclusions: Among low-income patients with prostate cancer, low self-efficacy for interacting with physicians was best predicted by diminished overall satisfaction with care, low confidence in providers, and worse symptom distress. Men with low self-efficacy fared worse over a range of psychosocial outcomes and both general and disease-specific health-related quality of life.

Objective: Patients with large prostate volumes undergoing interstitial brachytherapy (BT) are currently believed to have worse urinary symptoms and quality of life (QOL) following the implant. We sought to determine if data from patients treated with neoadjuvant androgen ablation followed by BT at our institution supported this notion using a cross-sectional study design., Methods: From 14 March 1997 to 25 August 2000, 248 patients underwent neoadjuvant androgen ablation followed by BT monotherapy (BTM) or BT combined with external beam (BTC) for treatment of localized prostate cancer. FACT-G and AUASS questionnaires were mailed to all patients on 1 September 2001. Overall FACT-G scores along with the irritative (IAUA) and obstructive (OAUA) subscales of the AUASS were calculated for each patient. Prostate volume (one to two weeks prior to BT), number of seeds, and implant method (ultrasound or CT guided) were compared with the outcomes on the two validated instruments. All analyses were adjusted for time since procedure and patient age., Results: 169 of 248 (68%) patients returned questionnaires. The median prostate volume was 37cc and number of seeds implanted was 95. Our data shows little correlation between total FACT-G or AUASS scores and volume of the prostate. Likewise, neither FACT-G nor IAUA scores appeared related to the number of seeds implanted. A correlation was seen when comparing number of seeds with OAUA scores, but this result appeared to be driven by the BTC group. Number of needles implanted did not appear to be related to total FACT-G scores. The number of needles inserted was related to both IAUA and OAUA scores in the BTC group, but not in BTM group., Conclusion: Quality of life and urinary function scores do not appear to be strongly related to pre-implant prostate volume or method of implantation and thus patients should not be dissuaded from considering neoadjuvant androgen ablation followed by BT solely due to prostate size.

Purpose: In several of the initial patients undergoing brachytherapy at our institution radioactive implants were visible in the thorax on chest radiography. The clinical ramifications of this unanticipated finding were unclear. Thus, we investigated the incidence of brachytherapy seed migration to the chest and whether these seeds were associated with any clinical significance., Materials and Methods: We retrospectively reviewed the records of all patients who underwent ultrasound or computerized tomography guided brachytherapy of 103palladium seeds from March 1997 to March 1999. This list of patients on brachytherapy was then matched against the radiology computer system to determine those who had undergone chest X-ray after brachytherapy. When the radiology report was unclear regarding brachytherapy seeds, chest x-rays were reviewed by one of us (R. O.) to determine the presence and position of the seeds., Results: Post-brachytherapy chest x-rays were available in 110 of the 183 patients. In 78 cases no brachytherapy seeds were identified. Radioactive implants were identified on chest radiography in 32 patients (29%), including 1 to 5 seeds in 20, 8, 1, 2 and 1, respectively. No patients complained of any change in pulmonary symptoms after brachytherapy., Conclusions: Radioactive implants migrated after brachytherapy for localized prostate cancer in 29% of the patients who underwent post-procedure radiography. There did not appear to be a pattern to the seed distribution. However, while the incidence was not negligible, no patient appeared to have any acute pulmonary symptoms. Therefore, while the migration of radioactive implants to the chest is a real phenomenon, it appears to have no adverse clinical consequences in the early post-procedure period.

Despite the fact that cancer cells can be found in many vascular beds, continued growth of the metastatic tumor focus exhibits a significant degree of 'organ tropism', with only certain organs exhibiting the ravages of metastatic disease. Since a limiting factor to the growth of metastases beyond 2 mm in diameter, may be a lack of angiogenesis, we sought to determine whether tumor overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic factor related to prostate cancer metastasis, is causally related to organ specific tumor growth in a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human prostate cancer cell line LnCaP which unlike its parent, has a predilection for growth in bone, a common site for human prostate cancer metastasis. LnCaP-C4-2, is tumorigenic when injected intrafemorally in mice but requires co-injection of stromal components (Matrigel) to be tumorigenic in the subcutaneous site. Because of this site-specific tumorigenicity profile and relatively low VEGF mRNA and protein expression, this line was transfected with a full length cDNA encoding the 165 isoform of VEGF. Cells either overexpressing or not expressing the transfected gene were selected for study in vivo and in vitro. Overexpression of VEGF did not seem to affect in vitro cell growth. Such overexpression did affect tumorigenicity and in vivo tumor growth rates when cells were inoculated in the subcutaneus site. Interestingly, the dependency of subcutaneous tumorigenicity on Matrigel co-inoculation was still observed in cells overexpressing VEGF. In contrast to the impact that VEGF overexpression has on subcutaneous tumorigenicity, no such effect was observed when cells were inoculated in orthotopic/prostate (primary) or intrafemoral (metastatic) sites. In view of the importance of tumor-stromal interactions in growth of xenografts, we sought to determine if the host strain is important to the observed tumorigenicity effects of VEGF overexpression. No differences in subcutaneous tumorigenicity as a function of either Matrigel use or VEGF expression levels were observed when SCID/bg and RAG/pfp mouse strains were compared. In conclusion, our data indicate that the biological impact of prostate tumor VEGF overexpression is organ/site specific, leading to the speculation that it may play a part in the observed organ tropism of metastatic spread. In addition, these results highlight the importance of the tumor microenvironment in determining the biological impact of transfected and overexpressed genes in the study of tumor biology.