Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Current Trends and Challenges of Microbiome Research in Bladder Cancer.

PURPOSE OF THE REVIEW: Microbiome research has provided valuable insights into the associations between microbial communities and bladder cancer. However, this field faces significant challenges that hinder the interpretation, generalization, and translation of findings into clinical practice. This review aims to elucidate these challenges and highlight the importance of addressing them for the advancement of microbiome research in bladder cancer. RECENT FINDINGS: Recent findings underscore the complexities involved in microbiome research, particularly in the context of bladder cancer. Challenges include low microbial biomass in urine samples, potential contamination issues during collection and processing, variability in sequencing methods and primer selection, and the difficulty of establishing causality between microbiota and bladder cancer. Studies have shown the impact of sample storage conditions and DNA isolation kits on microbiome analysis, emphasizing the need for standardization. Additionally, variations in urine collection methods can introduce contamination and affect results. The choice of 16S rRNA gene amplicon sequencing or shotgun metagenomic sequencing introduces technical challenges, including primer selection and sequencing read length. Establishing causality between the microbiota and bladder cancer requires experimental methods like fecal microbiota transplantation and human microbiota-associated murine models, which face their own set of challenges. Translating microbiome research into therapeutic applications is hindered by methodological variability, incomplete understanding of bioactive molecules, imperfect animal models, and the inherent heterogeneity of microbiome communities among individuals. Microbiome research in bladder cancer presents significant challenges stemming from technical and conceptual complexities. Addressing these challenges through standardization, improved experimental models, and advanced analytical approaches is essential for advancing our understanding of the microbiome's role in bladder cancer and its potential clinical applications. Achieving this goal can lead to improved patient outcomes and novel therapeutic strategies in the future.

Population Estimates of Ovarian Cancer Risk in a Cohort of Patients with Bladder Cancer.

BACKGROUND AND OBJECTIVE: The rationale for oophorectomy during female cystectomy is not adequately supported. The co-occurrence and timing of bladder cancer (BC) and ovarian cancer (OC) in females harboring OC germline mutations remain unclear. Our objective was to determine the frequency and temporal occurrence of OC germline variants among females with BC. METHODS: We used genetic and phenotypic data from the UK Biobank (UKB). The study cohort was defined using ICD-10/ICD-9 codes for BC and further stratified to identify 1347 females. Analysis was restricted to variants with high/moderate impact for initial regression. ClinVar was used to interpret pathogenicity. Pathogenic/likely pathogenic (P/LP) variants were assessed by age of presentation, family history, and concomitant malignancies. Statistical analysis was performed using UKB DNAnexus JupyterLab and RStudio. KEY FINDINGS AND LIMITATIONS: Some 3.4% of the patients had at least one of 15 variants for OC. CHEK2 and PALB2 mutations represented the highest ratio of overall/pathogenic variants (15.8% and 6.6%). Although females with P/LP OC mutations had a higher risk of OC, diagnosis of OC preceded BC by 11.3 yr (±12.5 yr) in the group with mutations and by 15.6 yr (±11.3 yr) in the group without mutations. The group with P/LP variants had higher rates of maternal (14.63% vs 8.12%; p = 0.04) and sibling (9.76% vs 3.98%; p = 0.02) breast cancer and of maternal colon cancer (9.76% vs 4.21%), and lower maternal life expectancy (75.34 vs 68.15 yr; p = 0.0014). UKB provides limited staging/treatment history and its exome sequencing platform may miss variants or provide insufficient coverage for genotyping. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study provides evidence against routine oophorectomy for reducing OC risk in females with BC. The results highlight that the development of OC occurred 11 yr before diagnosis of BC for patients with OC mutations and 15 yr before diagnosis of BC for patients without OC mutations. PATIENT SUMMARY: Although removal of the ovaries in women with bladder cancer is common, no studies have shown that this strategy has a benefit. Our study of women diagnosed with bladder cancer who had genetic mutations associated with ovarian cancer shows that their risk of developing ovarian cancer after bladder cancer is low. These findings provide evidence against removal of the ovaries when the bladder is being removed as treatment for bladder cancer.

Targeting bladder cancer: A sex sensitive perspective in mutations and outcomes.

The incidence of bladder cancer (BC) is more common in males, however, the clinical outcome for females tends to be more unfavorable, as demonstrated by a 21% increase in mortality compared to males within two years of diagnosis. While it was previously believed that the differences in outcome were solely the result of differences in sex chromosomes and hormones, it is now acknowledged that a more intricate interplay of factors is at play. By acquiring a more comprehensive understanding of these sex-specific effects, future efforts in precision medicine can be customized to an individual's biological sex. This narrative review aims to summarize our knowledge of the molecular classification of sex differences in BC by compiling the existing evidence on genetic disparities between males and females and evaluating these disparities in both noninvasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Our findings emphasize the significance of considering sex as a factor in future clinical trials and registry studies due to established differences in immune composition, molecular profiling, and genetic mutations between males and females. Further investigation into the molecular processes involved in the evasion or resistance of immune-based therapies, such as Bacillus Calmette-Guérin and other immunotherapies, is essential to identify markers of response or resistance that vary between male and female patients. This will aid in optimizing treatment and promoting equitable outcomes, particularly in NMIBC cases.

The role of cytoreductive nephrectomy in the immuno-oncological therapy era.

PURPOSE OF REVIEW: Cytoreductive nephrectomy has had a variable role in the management of metastatic renal cell carcinoma (RCC) through the different systemic therapy eras. Initially felt to be beneficial with interferon, the utility of cytoreductive nephrectomy was called into question in the tyrosine kinase inhibitor (TKI) era. However, with the advent of immunotherapy for metastatic RCC, the role of cytoreductive nephrectomy continues to be debated. This study sought to evaluate the recent literature and discuss cytoreductive nephrectomy within the context of an improved systemic therapy era. RECENT FINDINGS: The literature that exists on the use of cytoreductive nephrectomy with immunotherapy is retrospective in nature and largely derived from large, institutional databases. Although smaller, single-institution articles exist and provide more granular data, issues concerning selection bias and unmeasured confounders persist. Overall, the available studies demonstrate that patient selection is paramount, and cytoreductive nephrectomy should be reserved for patients with no more than one risk factor, those requiring palliation of local symptoms and for those patients with stable, low volume disease or with a complete response following systemic therapy exposure. SUMMARY: The optimal use of cytoreductive nephrectomy in metastatic RCC remains unclear, but certain subgroups of patients, on evaluation of post hoc and retrospective data, seem to benefit from surgical intervention.