Purpose Men are diagnosed with bladder cancer at 3 times the rate of women. However, women present with advanced disease and have poorer survival, suggesting delays in bladder cancer diagnosis. ...Hematuria is the presenting symptom in most cases. We assessed gender differences in hematuria evaluation in older adults with bladder cancer. Materials and Methods Using the SEER (Surveillance, Epidemiology and End Results) cancer registry linked with Medicare claims we identified Medicare beneficiaries 66 years old or older diagnosed with bladder cancer between 2000 and 2007 with a claim for hematuria in the year before diagnosis. We examined the impact of gender, and demographic and clinical factors on time from initial hematuria claim to urology visit and on time from initial hematuria claim to hematuria evaluation, including cystoscopy, upper urinary tract imaging and urine cytology. Results Of 35,646 patients with a hematuria claim in the year preceding bladder cancer diagnosis 97% had a urology visit claim. Mean time to urology visit was 27 days (range 0 to 377). Time to urology visit was longer for women than for men (adjusted HR 0.9, 95% CI 0.87–0.92). Women were more likely to undergo delayed (after greater than 30 days) hematuria evaluation (adjusted OR 1.13, 95% CI 1.07–1.21). Conclusions We observed longer time to a urology visit for women than for men presenting with hematuria. These findings may explain stage differences in bladder cancer diagnosis and inform efforts to decrease gender disparities in bladder cancer stage and outcomes.
Urothelial carcinoma of the bladder (UC) is the fifth most common cancer in the United States. Germline variants, especially rare germline variants, may account for a portion of the disparity seen ...among patients in terms of UC incidence, presentation, and outcomes. The objectives of this study were to identify rare germline variant associations in UC incidence and to determine its association with clinical outcomes. Using exome sequencing data from the DiscovEHR UC cohort (
= 446), a European-ancestry, North American population, the complex influence of germline variants on known clinical phenotypes were analyzed using dispersion and burden metrics with regression tests. Outcomes measured were derived from the electronic health record (EHR) and included UC incidence, age at diagnosis, and overall survival (OS). Consequently, key rare variant association genes were implicated in
and
The Kaplan-Meier survival analysis reveals that individuals with
germline variants had significantly worse OS than those without any (log-rank
-value = 3.46 × 10
). Those with
variants were found to be slightly more likely to have UC compared to a matched control cohort (FDR q-value = 0.116). These associations highlight several candidate genes that have the potential to explain clinical disparities in UC and predict UC outcomes.
Median age at bladder cancer (BC) diagnosis is older than for other major tumours. Age should not determine treatment, and patients should be fully involved in decisions. Patients should be screened ...with Mini-Cog™ for cognitive impairment and the G8 to ascertain need for comprehensive geriatric assessment. In non-muscle invasive disease, older adult patients should have standard therapy. Age does not contraindicate intravesical therapy. Independent of age and fitness, patients with muscle-invasive BC should have at least cross-sectional imaging. Data suggest extensive undertreatment in older adult patients, leading to poor outcomes. Standard treatment for a fit patient differs between countries. Radical cystectomy and trimodality therapy are first-line options. Radical cystectomy patients should be referred to an experienced centre and prehabilitation is mandatory. Older adult patients should be considered for neoadjuvant and adjuvant therapy, according to guidelines. In urinary diversion, avoiding bowel surgery for reconstruction of the lower urinary tract significantly reduces complications. If a patient is unfit for or refuses standard treatment, RT alone, or TURBT in selected cases should be considered. In metastatic BC, older adult patients should receive standard systemic therapy, depending on fitness for cisplatin and prognosis. Efficacy and tolerability of immunotherapy (IO) appears similar to younger patients. Second line IO is standard in platinum pre-treated patients, with benefit and tolerability in the older adult similar to younger patients. The toxicity profile seems to favour IO in the older adult but more data are needed. Patients progressing on IO may respond to further systemic treatment. In metastatic disease, palliative care should begin early.
•Of the major tumours, patients with bladder cancer (BC) are the oldest at diagnosis.•Treatment should be determined by fitness, prognosis and patient preference.•Undertreating non-invasive BC risks poor outcome; intravesical therapy is an option.•In invasive BC, consider radical cystectomy with prehab and trimodality therapy.•In advanced disease consider cisplatin in the fit. Immunotherapy could have a role.
One of the fundamental challenges in cancer is to detect the regulators of gene expression changes during cancer progression. Through transcriptional silencing of critical cancer-related genes, ...epigenetic change such as DNA methylation plays a crucial role in cancer. In addition, miRNA, another major component of epigenome, is also a regulator at the post-transcriptional levels that modulate transcriptome changes. However, a mechanistic role of synergistic interactions between DNA methylation and miRNA as epigenetic regulators on transcriptomic changes and its association with clinical outcomes such as survival have remained largely unexplored in cancer.
In this study, we propose an integrative framework to identify epigenetic interactions between methylation and miRNA associated with transcriptomic changes. To test the utility of the proposed framework, the bladder cancer data set, including DNA methylation, miRNA expression, and gene expression data, from The Cancer Genome Atlas (TCGA) was analyzed for this study.
First, we found 120 genes associated with interactions between the two epigenomic components. Then, 11 significant epigenetic interactions between miRNA and methylation, which target E2F3, CCND1, UTP6, CDADC1, SLC35E3, METRNL, TPCN2, NACC2, VGLL4, and PTEN, were found to be associated with survival. To this end, exploration of TCGA bladder cancer data identified epigenetic interactions that are associated with survival as potential prognostic markers in bladder cancer.
Given the importance and prevalence of these interactions of epigenetic events in bladder cancer it is timely to understand further how different epigenetic components interact and influence each other.
Aerococcus urinae is a rare organism isolated from urine cultures. We present a case of an 80 year-old male with bladder cancer and multimorbidity who developed A. urinae infection. A. urinae may ...cause simple and complicated UTIs, bacteremia, and endocarditis in older adults with multimorbidity, chronic urinary retention, or indwelling catheters. A. urinae treatment should employ penicillin, amoxicillin, and nitrofurantoin. Due to increasing antibiotic resistance, urine culture should include antibiotic susceptibility testing. Prompt and culture-specific treatment is critical to avoid clinical progression of the infection.
Eukaryotic organisms have developed a variety of mechanisms to regulate translation post-transcriptionally, including but not limited to the use of miRNA silencing in many species. One method of ...post-transcriptional regulation is through miRNAs that bind to the 3' UTRs to regulate mRNA abundance and influence protein expression. Therefore, the diversity of mRNA 3' UTRs mediating miRNA binding sites influence miRNA-mediated regulation. Alternative polyadenylation, by shortening mRNA isoforms, increases the diversity of 3' UTRs; moreover, short mRNA isoforms elude miRNA-medicated repression. Because no current prediction methods for putative miRNA target sites consider whether or not 1) splicing-informed miRNA binding sites and/or 2) the use of 3' UTRs provide higher resolution or functionality, we sought to identify not only the genome-wide impact of using exons in mRNA 3' UTRs but also their functional connection to miRNA regulation and clinical outcomes in cancer. With a genome-wide expression of mRNA and miRNA quantified by 395 bladder cancer cases from The Cancer Genome Atlas (TCGA), we 1) demonstrate the diversity of 3' UTRs affecting miRNA efficiency and 2) identify a set of genes clinically associated with mRNA expression in bladder cancer. Knowledge of 3' UTR diversity will not only be a useful addition to current miRNA target prediction algorithms but also enhance the clinical utility of mRNA isoforms in the expression of mRNA in cancer. Thus, variability among cancer patient's variability in molecular signatures based on these exon usage events in 3' UTR along with miRNAs in bladder cancer may lead to better prognostic/treatment strategies for improved precision medicine.
•EORTC calculator had acceptable accuracy to measure NMIBC outcomes.•NCCN framework was mediocre for predicting recurrence, adequate for progression.•Other clinicopathological factors and biomarkers ...may increase predictive accuracy.•Further innovation will need to incorporate treatment and recurrence subgroups.
To externally validate the European Organization for the Research and Treatment of Cancer (EORTC) risk calculator and National Comprehensive Cancer Network (NCCN) guidelines in a contemporary population of U.S. non–muscle-invasive bladder cancer (NMIBC) patients treated in a community-based setting and compare our findings to those from another U.S. health system.
We identified 1,491 NMIBC patients with a median follow-up of 2.1 years (recurrence) and 4.1 years (progression). We calculated NCCN risk groupings and EORTC prognostic index for recurrence and progression. We followed Royston and Altman's guidelines for the external validation of prognostic calculators.
For predicting recurrence using the EORTC framework, Harrell's C (a measure of discrimination) was smaller in our sample (0.66) than in the European Association of Urology sample (0.61), whereas for progression, Harrell's C was larger in our sample (0.78 vs. 0.75). The EORTC calculator overestimated progression risk in the highest stratum for our sample; calibration and discrimination were adequate for all groups except the highest risk group. For NCCN risk groupings, Harrell's C was 0.54 for recurrence and 0.62 for progression, suggesting poor to fair discrimination in our sample. The NCCN framework had slightly better performance for predicting progression vs. recurrence.
Existing NMIBC risk-stratification frameworks have acceptable accuracy to predict outcomes. However, further innovation in NMIBC care will require predictive tools with more granularity to reflect the differential risks of subgroups of NMIBC recurrence, prior treatment histories, and other prognostic variables.
Abstract With an aging American population, patient complexity is increasing because of multiple chronic conditions. Multiple chronic conditions are associated with health care costs, utilization, ...and poor functional status. Superficial bladder cancer predominates in the elderly and can be considered a chronic condition in its own right because of frequent surveillance and treatment. A patient-centered approach for superficial bladder cancer is needed that takes into account competing risks from chronic conditions, functional status, and patient preferences in the elderly.
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