Comparing costs associated with management of antibiotic-recalcitrant recurrent urinary tract infections for one year pre- and post-electrofulguration.

INTRODUCTION: To quantify and compare recurrent urinary tract infection costs between 1 year before and 1 year after electrofulguration. METHODS: Following IRB approval, a well-characterized cohort of non-neurogenic women with >3 symptomatic urinary tract infections (UTIs)/year, a negative upper and lower urinary tract evaluation, and inflammatory bladder lesions (cystitis) on office cystoscopy who underwent fulguration of these lesions was analyzed. Cost of visits, imaging, labs, and medications were summed for 1-year pre- and post-fulguration using the Medicare Physician Fee Schedule, local pharmacy pricing, and institutional expenses. Before fulguration, all patients underwent clinic visit, noninvasive flow study, and flexible cystoscopy, and post-fulguration, 6-week follow-up visit and 6-month cystoscopy. RESULTS: Ninety-three women met study criteria (mean age 64), with 100% 1-year follow-up. Before fulguration, 73% of patients used daily antibiotic suppression, 6% self-start antibiotics, and 5% postcoital prophylaxis. Some also used vaginal estrogens (17%), urinary analgesics (13%), and cranberry or d-mannose supplements (7%). At 1 year post-fulguration, 82% had 0-1 infections and no cystoscopy evidence of cystitis, while 14% required additional fulguration for new cystitis sites and recurrent infections. Patients had on average 0.7 infections in the 1-year post-fulguration, which was significantly lower than pre-fulguration (p < 0.05). Mean 1-year pre-fulguration cost was $1328 (median $1071, range $291-$5564). Mean 1-year post-fulguration cost was $617 (median $467, range $275-$4580). On average, post-fulguration costs were $710 lower than pre-EF (p < 0.05). CONCLUSION: For women with antibiotic-refractory recurrent urinary tract infections and cystoscopy evidence of cystitis, fulguration was associated with a significant reduction in UTI-related costs in the 1-year post-fulguration.

Brachytherapy and external beam radiation in the management of primary penile cancer - Game changer for organ preservation?

OBJECTIVE: In squamous cell carcinoma of the penis (PeCa), treatment options for primary tumors vary by disease stage and may include surgery, radiation, topical chemotherapy, or laser excision. This review aims to highlight the current evidence on the value of radiotherapy as an organ-preserving strategy in primary PeCa. MATERIAL AND METHODS: Manuscripts on primary PeCa treatment with external beam radiotherapy (EBRT) and brachytherapy were evaluated via Scopus, PubMed/MEDLINE, and Web of ScienceTM (2013-2023) to assess their efficacy and safety. Animal studies, studies with <5 patients, and case reports were excluded. RESULTS: Radiotherapy offers the potential for organ preservation with tumor control rates comparable to radical surgery, while disease-specific survival rates up to 70 % were experienced with EBRT. Brachytherapy (BT) is the preferred method of irradiation for glans-limited tumors, whereas a higher relapse risk is expected for tumors >4 cm. BT shows 73 % amputation-free survival at 8-10 years and 81 % progression-free survival at 5-10 years. Compared with BT, total amputation significantly improves 5-year disease-free survival rate. BT offers a superior 5-year local control and penile preservation rates compared to EBRT. Common acute toxicities of brachytherapy include radiodermatitis, sterile urethritis, and urethral adhesions. The primary late adverse events of BT are soft tissue necrosis (0-31 %) and meatal stenosis (0-43 %). CONCLUSION: BT is a favorable radiation modality, offering an efficient and conservative approach. HDR BT is favored for its enhanced dose distribution and radiation protection. Collaboration between radiation oncologists and urologists is essential in order to provide an optimal patient selection and manage toxicities thus optimizing patient outcomes.

Bladder-resident bacteria associated with increased risk of recurrence after electrofulguration in women with antibiotic-recalcitrant urinary tract infection.

Background: Antibiotic-recalcitrant recurrent urinary tract infection (rUTI) is has become increasingly observed in postmenopausal women. Therefore, when standard antibiotic therapies have failed, some elect electrofulguration (EF) of areas of chronic cystitis when detected on office cystoscopy. EF is thought to remove tissue-resident bacteria that have been previously detected in the bladder walls of postmenopausal women with rUTI. We hypothesized that increased bladder bacterial burden may be associated with incomplete rUTI resolution following EF. Methods: Following IRB approval, bladder biopsies were obtained from 34 consenting menopausal women electing EF for the advanced management of rUTI. 16S rRNA FISH was performed using both universal and Escherichia probes and tissue-resident bacterial load was quantified. Time to UTI relapse after EF was recorded during a six-month follow-up period and the association of bladder bacterial burden and clinical covariates with UTI relapse was assessed. Results: We observed bladder-resident Escherichia in 52% of all participants and in 92% of participants with recent E. coli UTI. Time-to-relapse analysis revealed that women with high bladder bacterial burden as detected by the universal probe had a significantly ( p =0.035) higher risk of UTI within six months of EF (HR=3.15, 95% CI: 1.09-9.11). Interestingly, bladder-resident Escherichia was not significantly associated ( p =0.26) with a higher risk of UTI relapse (HR= 2.14, 95% CI: 0.58-7.90). Conclusions: We observed that total bladder bacterial burden was associated with a 3.1x increased risk of rUTI relapse within six months. Continued analysis of the relationship between bladder bacterial burden and rUTI outcomes may provide insight into the management of these challenging patients.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Bacterial species cultured after electrofulguration in women with a history of antibiotic-recalcitrant urinary tract infections frequently compare with pre-fulguration findings: a pilot study.

Electrofulguration (EF) of areas of chronic cystitis in women with antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) can result in improvement of their urinary tract infections (UTIs). We compared urine culture (UC) findings in patients before and after EF, as well as how they vary with cystitis stage at the time of EF, to evaluate for persistent species. After obtaining institutional review board approval, we retrospectively reviewed a prospectively maintained database of EF patients for those with positive UC findings in the 3-6 months preceding EF. Patient pre-EF UC was then compared with first positive UC after EF prompted by a new symptomatic UTI episode, with the hypothesis that the same species will be identified before and after EF. Exclusion criteria included UC from outside institution, neurogenic bladder, and need for catheterization. Ninety-nine women with pre- or post-EF UC-recorded organisms met the study criteria. The median age was 65 years (interquartile range 64-74), with a median time to first positive culture following fulguration of 9.7 months. For 26 patients with positive cultures both pre- and post-EF, the same organism was present in both cultures in 73% of the patients, with predominantly Escherichia coli. EF was effective at reducing the rate of UTIs in this population. For women undergoing EF for antibiotic-recalcitrant RUTIs and associated chronic cystitis lesions, 73% of those with a UC obtained at the time of a first symptomatic recurrent UTI episode post-EF expressed the same organism as before EF. Further study is needed to better understand the evolution of the microbiome post-EF.IMPORTANCEAmong women who experience a recurrent urinary tract infection after a fulguration procedure on areas of chronic cystitis in their bladder, there are no data available on whether the bacterial species found in urine cultures are the same or different from those present before fulguration. By removing the inflamed surface layer of cystitis during fulguration, it is possible that the procedure unmasks deep-seated bacteria. The bacterial kingdom in the bladder wall of these chronically infected women may be different from what is expressed sporadically in urine cultures. Confirming prior studies, we found that fulguration in women with antibiotic-recalcitrant recurrent urinary tract infections and cystitis lesions was effective at reducing the rate of urinary tract infections. At the time of a first symptomatic recurrent UTI episode post-fulguration, 73% expressed the same organism in urine culture as before fulguration. Further study is needed to better understand the evolution of the microbiome post-EF. This article evaluates persistent infections after electrofulguration of areas with chronic cystitis in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections. Pre-fulguration urine cultures were compared with the first positive urine culture prompted by a new symptomatic UTI episode after electrofulguration, with the hypothesis that the same species will be identified before and after the fulguration procedure. Electrofulguration was effective at reducing the rate of UTIs in this population. However, 73% of those with a urine culture obtained at the time of a first symptomatic recurrent UTI episode post-electrofulguration expressed the same organism (predominantly Escherichia coli) as before the fulguration procedure. Further study is needed to better understand the evolution of the microbiome after electrofulguration.

Genome sequencing of correlated pathogenic Escherichia coli and Enterococcus associated with recurrent urinary tract infections.

Reported here are the sequences for 11 Escherichia coli and four Enterococcus strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the Enterococcus strains were isolated along with an E. coli strain. This provides a resource of high-quality complete genomes from polymicrobial infections.

Current Status and Challenges in Rare Genitourinary Cancer Research and Future Directions.

PURPOSE OF REVIEW: In contemporary urological practice, managing rare genitourinary (GU) malignancies presents significant challenges, necessitating a comprehensive understanding of their unique characteristics and tailored treatment approaches. RECENT FINDINGS: Rare GU malignancies, whether per se, variants of common histologies, or common tumors in uncommon locations, often lack widely available clinical guidelines. Consequently, treatment decisions are frequently based on empirical evidence, risking suboptimal outcomes. However, recent advances in molecular profiling, targeted therapies, and immunotherapy offer promising avenues for improving management strategies and patient outcomes. This review provides a comprehensive overview of some rare GU malignancies encountered in clinical practice, including their distinct pathological features, current management approaches, and ongoing research directions. Understanding the complexities of these rare tumors and implementing multidisciplinary treatment strategies are essential for optimizing patient care and improving survival outcomes.

Systematic Review of the Global Use of Validated Questionnaires in the Management of Stress Urinary Incontinence in Women.

INTRODUCTION: Our goal was to systematically review the most commonly used validated questionnaires in recent global literature on stress urinary incontinence (SUI) treatment. METHODS: PubMed, Embase, and Ovid databases were queried for manuscripts containing "female stress urinary incontinence" AND "diagnosis" AND "treatment" AND "questionnaire." Two independent reviewers screened studies for randomized controlled trials, prospective, and retrospective studies between 2018 and 2023. Exclusion criteria included male participants, non-SUI incontinence, and articles not originally written in English. The review was registered in PROSPERO [465721] and conformed to PRISMA guidelines. RESULTS: In 117 manuscripts meeting study criteria, the median of the mean ages was 52 years, with a median of 164 participants per study. Most studies originated in Europe (59/117). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was the most frequently used (52%), followed by the Patient Global Impression of Improvement (31%), the Urinary Distress Inventory 6 Short Form (25%), the Incontinence Quality of Life (20%), and the Incontinence Impact Questionnaire Short Form (19%). These leading questionnaires were short, translated into several languages, and globally addressed important SUI-related domains, including the presence and severity of SUI, additional lower urinary tract symptoms, and the impact of SUI on quality of life, as well as changes perceived after treatment. CONCLUSIONS: This systematic review of the validated questionnaires used in contemporary SUI management literature could help guide recommendations for incorporating these favored instruments into future SUI treatment outcome documents.

Management of Bulky Inguinal and Pelvic Lymph Nodes.

Penile cancer with bulky inguinal metastasis has a high probability of harboring pathologically involved lymph nodes best managed in a multidisciplinary care setting. Appropriate staging with cross-sectional imaging and fine-needle aspirate cytology of suspicious nodes guide decision-making for the use of platinum-based neoadjuvant chemotherapy followed by inguinal lymph node dissection. Surgical resection plays an important diagnostic, therapeutic, and guiding role in disease management. Patients with adverse pathologic features, especially those with extranodal disease extension, may derive additional benefit from adjuvant radiotherapy.

Overview of Systemic Therapies in Penile Cancer.

Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common histologic subtype of PC, accounting for approximately 95% of cases. With limited therapeutic options available, systemic therapies have emerged as critical components in the management of advanced PSCC. Recent developments in clinical research have revealed the effectiveness of new therapeutic strategies. By elucidating the mechanism of action and clinical evidence supporting these treatments, we strive to offer insights into optimizing treatment strategies and enhancing the quality of care for patients affected by this complex disease.

Immune-based Therapies for Penile Cancer.

This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing on immunotherapy, vaccine therapy, and cell-based treatments, especially in the context of human papillomavirus-related PSCC. Factors influencing these therapies are discussed. These include the immune microenvironment, programmed cell death ligand-1 expression, and tumor immune cell infiltration. This article also highlights immune checkpoint inhibitors and related clinical trials. This review supports the use of personalized medicine in treating PSCC. It stresses the need for collaborative studies and data sharing to create specific treatment plans and achieve better outcomes.

The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies.

CONTEXT: Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities. OBJECTIVE: To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors. EVIDENCE ACQUISITION: A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs). EVIDENCE SYNTHESIS: Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender. CONCLUSIONS: Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

From Detection to Cure - Emerging Roles for Urinary Tumor DNA (utDNA) in Bladder Cancer.

PURPOSE OF REVIEW: This review sought to define the emerging roles of urinary tumor DNA (utDNA) for diagnosis, monitoring, and treatment of bladder cancer. Building from early landmark studies the focus is on recent studies, highlighting how utDNA could aid personalized care. RECENT FINDINGS: Recent research underscores the potential for utDNA to be the premiere biomarker in bladder cancer due to the constant interface between urine and tumor. Many studies find utDNA to be more informative than other biomarkers in bladder cancer, especially in early stages of disease. Points of emphasis include superior sensitivity over traditional urine cytology, broad genomic and epigenetic insights, and the potential for non-invasive, real-time analysis of tumor biology. utDNA shows promise for improving all phases of bladder cancer care, paving the way for personalized treatment strategies. Building from current research, future comprehensive clinical trials will validate utDNA's clinical utility, potentially revolutionizing bladder cancer management.

Systematic Review of the Global Literature on Uncomplicated Recurrent Urinary Tract Infections in Women: Underscoring Major Heterogeneity.

OBJECTIVE: To examine the global literature database on uncomplicated recurrent urinary tract infections (rUTI), this systematic review assesses the availability of rUTI data based on geographic region and elucidates the current state of research and gaps in knowledge. METHODS: The databases PubMed, Embase, WHO Global Index Medicus, and SciELO were searched for keywords related to rUTI between 2000 and 2023. Three independent reviewers screened studies restricted to female participants age ≥18 years with uncomplicated rUTIs. Studies were excluded if they did not provide a definition for rUTI or did not cite or report an estimate for rUTI prevalence. The review was registered in PROSPERO and conformed to PRISMA guidelines. RESULTS: The search yielded 2947 studies of which 124 were ultimately included. Convenience samples were used for 91% of studies and sample sizes were 30% n <50, 29% n = 50-99, 22% n = 100-199, 36% n ≥200. Most studies were conducted in Europe (41%) or North America (39%), were prospective (52%), at tertiary centers (49%) and included all ages ≥18 (60%). The most common definition for rUTI was 2 UTI/6 m or 3 UTI/1y (62%). Regardless of study location, most studies cited prevalence estimates for rUTI derived from U.S.-based populations. CONCLUSION: This study represents the first formal investigation of the global literature base on uncomplicated rUTI. Studies on rUTIs are globally of small scale and definitions used for rUTI are heterogeneous. More studies are needed to ascertain the true prevalence of rUTI outside of North America and Europe.

Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.

NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.