Prognostic Value of Liquid-Biopsy-Based Biomarkers in Upper Tract Urothelial Carcinoma.

Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.

Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer.

Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

Prognostic implication of TERT promoter mutation and circulating tumor cells in muscle-invasive bladder cancer.

PURPOSE: Current clinical prognostic factors are not accurate enough to identify and monitor those muscle-invasive bladder cancer (MIBC) patients at high risk of progression after radical cystectomy (RC). Here, we determined genetic alterations in the tumor and circulating tumor cell (CTC) enumeration to find biomarkers useful for the management of MIBC after RC. METHODS: Thirty-nine MIBC patients undergoing RC were included. Tumoral tissue DNA was analyzed by next generation sequencing. CTCs were isolated from blood collected before RC and one, four and 12 months later. RESULTS: Sixteen (41%) patients progressed in a median time of 8.5 months and 11 (69%) of these patients harbored the TERT c.-124C > T mutation. All progressive patients harboring the TERT c.-124C > T mutation presented a significant increase in CTC number 12 months after RC compared to those without the mutation. Additionally, CTC number at 12 months was identified as an independent prognostic biomarker for tumor progression and cancer specific survival (CSS). Ten (63%) progressive patients showed an increment of CTC number with a median anticipation period of four months compared with imaging techniques. CONCLUSIONS: The TERT c.-124C > T mutation could be considered a biomarker of aggressivity. CTC enumeration is a useful tool for identifying MIBC patients at high risk of progression and CSS after RC and for detecting tumor progression earlier than imaging techniques.

Urine Gene Expression Profiles in Bladder Pain Syndrome Patients Treated with Triamcinolone.

BACKGROUND: The pathogenesis of bladder pain syndrome (BPS) remains incompletely defined, and there is no standard treatment for BPS as yet. OBJECTIVE: To gain detailed insight into the disease pathobiology of BPS through comparative gene expression analysis of urine from BPS patients versus control individuals and, furthermore, to determine the efficacy of triamcinolone treatment in BPS patients in terms of the gene expression profiles in urine. DESIGN, SETTING, AND PARTICIPANTS: A prospective pilot study including 21 urine samples from patients with Hunner's lesions (n=6) and controls (n=9) between January and August 2017. INTERVENTION: Triamcinolone treatment of BPS patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urine samples from BPS patients were collected before (pretreatment group) and 2 wk after triamcinolone treatment (post-treatment group). Gene expression of urine sediment was analyzed using RNA sequencing. Pathways and biological processes in which differentially expressed genes are involved were analyzed. RESULTS AND LIMITATIONS: A total of 3745 genes were found to be differentially expressed between the three groups tested. Gene expression differences between controls and BPS samples (630 differentially expressed genes) were more pronounced than the differences between pre- and post-treatment BPS samples (197 differentially expressed genes). Gen Set Enrichment Analysis showed that differentially expressed genes in BPS patients (pretreatment), compared with controls, were enriched for some functional gene networks associated with several metabolic processes and ribosome biogenesis. The limited number of patients included may not accurately represent the BPS population. CONCLUSIONS: Gene expression profiles of urine sediment are able to discriminate between BPS and control patients. Moreover, we show that triamcinolone induces changes in urine gene expression profiles. PATIENT SUMMARY: In this report, we looked at gene expression profiles of urine sediment from patients with Hunner's lesions, before and after triamcinolone treatment, and control individuals. We found that urine gene expression profiles are able to discriminate Hunner's lesions patients from controls. Furthermore, we report, for the first time, that triamcinolone treatment of patients with Hunner's lesions induces changes in bladder gene expression profiles that can be observed in urine samples.

Health-related quality of life in patients with urostomies.

PURPOSE: To assess health-related quality of life in patients with urothelial (bladder) cancer 6 months following radical cystectomy with construction of a urostomy. SUBJECTS: The target sample was 54 patients with urothelial cancer who underwent radical cystectomy with Bricker-type incontinent urinary diversion between December 2008 and December 2009; 37 out of 54 (68%) of potential respondents agreed to participate. Seven potential subjects died within the 6-month period and we were unable to locate 10 potential respondents. INSTRUMENT: The Stoma-Quality of Life was developed to be valid for measurement of 20 items that query the impact of the ostomy on the health-related quality of life and its impact on daily life. Scores were categorized as 70% to 100% (indicating good quality of life), 30% to 69% (indicating moderate quality of life), and 0 to 29% (indicating poor quality of life). METHODS: Subjects responded to the Stoma-Quality of Life questionnaire by telephone 6 months after urostomy surgery. RESULTS: Thirty-five were ranked as having a good quality of life. The remaining 2 subjects had scores indicating moderate quality of life; no respondent was ranked as having a poor quality of life. CONCLUSIONS: Health-related quality of life was ranked as good in 95% of a group of patients managed by radical cystectomy and Bricker ileal conduit construction and moderate in 5%. Based on these findings, we conclude that the Bricker-type incontinent urinary diversion remains a viable treatment option for bladder cancer that allows an acceptable health-related quality of life.

Impact of a nurse-run clinic on prevalence of urinary incontinence and everyday life in men undergoing radical prostatectomy.

PURPOSE: To determine the prevalence of urinary incontinence (UI) in patients undergoing prostatectomy and to evaluate the impact of UI on the everyday life in order to select the patients eligible to enter a pelvic floor rehabilitation program. SUBJECTS AND SETTINGS: The sample comprised 114 consecutive men undergoing laparoscopic or open radical prostatectomy between April 2007 and April 2008. Participants' mean age was 59 years (range, 46-67 years). The research setting was a hospital-based clinic in Barcelona, Spain. Patients who required an indwelling urinary catheter due to other factors were excluded from the trial. During admission, nursing staff explained the study and obtained informed consent from patients willing to participate in the trial. METHODS: The impact of UI on daily living was evaluated via administration of the International Consultation on Incontinence Questionnaire-Short Form. Impact of UI was evaluated before surgery, and after 1 and 12 months following indwelling catheter removal. RESULTS: A total of 95.5% patients developed UI 1 month following bladder catheter removal. Slightly less than 1 in 4 patients (24.8%) indicated that UI had no effect on activities of daily living. In contrast, 27.5% indicated that UI had a moderate impact and 47.7% indicated a severe impact. Ninety-one patients reported performing pelvic floor muscle exercises to improve UI, but only 45% were found to be performing them correctly. When evaluated at 1 year following catheter removal, 52.64% of the patients continued to experience UI. The majority (79.8%) indicated that UI did not impact their daily lives, 8.8% indicated a moderate impact, and 20.4% reported that UI had a severe impact on daily life. Seventy patients (61.4%) continued to perform pelvic floor muscle exercises; after 1 year, 93% were deemed to be correctly identifying, contracting, and relaxing their pelvic floor muscles. CONCLUSIONS: Urinary incontinence remains prevalent as long as 12 months following catheter removal. Incontinence exerts a moderate to severe impact on daily life in 27.5% to 20.4% of respondents. In order to minimize the negative impact as much as possible, we advocate a pelvic floor muscle training program overseen by RNs.

Nursing care program for erectile dysfunction after radical prostatectomy.

The prevalence of erectile dysfunction (ED) in 114 patients with prostate cancer treated with radical prostatectomy was examined to determine the efficacy of an ED care program in which nurse-provided education plays a fundamental role in the detection and follow-up of ED as well as in treatment compliance. The nursing program consists of four visits during which specific treatment-related information, education and support, active listening, and selection of the treatment best suited to each patient (in consultation with the healthcare team) are provided. One month following bladder catheter removal, 77 of the 114 patients (69%) in the study had ED, with a majority suffering from severe ED. A nursing care program could help minimize ED and enable patients to adapt to their new situation.