Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades.

Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field. Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review. Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging. Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.

Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial [version 2; peer review: 2 approved].

Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS).  Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials.

A Review of Modern Imaging Landscape for Prostate Cancer: A Comprehensive Clinical Guide.

The development of prostate cancer imaging is rapidly evolving, with many changes to the way patients are diagnosed, staged, and monitored for recurrence following treatment. New developments, including the potential role of imaging in screening and the combined diagnostic and therapeutic applications in the field of theranostics, are underway. In this paper, we aim to outline the current landscape in prostate cancer imaging and look to the future at the potential modalities and applications to come.

Infection after ureteroscopy for ureteric stones: analysis of 71 305 cases in the Hospital Episode Statistics database.

OBJECTIVES: To investigate the burden of infectious complications following ureteroscopy (URS) for ureteric stones on a national level in England using data from the Hospital Episodes Statistics (HES) data warehouse. MATERIALS AND METHODS: A retrospective cohort was identified and followed up in HES during the period April 2013 to March 2020 for all procedure codes relating to ureteroscopic stone treatment (M27.1, M27.2, M27.3). Treatment episodes relating to the first URS ('index ureteroscopy') for each patient were further analysed. All subsequent admissions within 30 days were also captured. The primary outcome was diagnosis of urinary tract infection (UTI; including all codes relating to a UTI/sepsis within the first 30 days of index URS). Secondary outcomes were critical care attendance, attendance at the accident and emergency department (A&E) within 30 days, and mortality. RESULTS: A total of 71 305 index ureteroscopies were eligible for analysis. The median age was 55 years, and 81% of procedures were elective and 45% were undertaken as day-cases. At the time of index URS, 16% of patients had diabetes, 0.5% had coexisting neurological disease and 40% had an existing stent/nephrostomy. Overall, 6.8% of the cohort (n = 4822) had a diagnosis of UTI within 30 days of index URS (3.9% immediately after surgery). A total of 339 patients (0.5%) required an unplanned stay in critical care during their index URS admission; 8833 patients (12%) attended A&E within 30 days. Overall mortality was 0.18% (60 in-hospital, 65 within 30 days); 40 deaths (0.056%) included infection as a contributing cause of death. CONCLUSION: We present the largest series evaluating infectious complications after ureteroscopic stone treatment. The procedure is safe, with low inpatient infective complication and critical care admission rates.

Xanthogranulomatous pyelonephritis: a review and meta-analysis with a focus on management.

PURPOSE: Xanthogranulomatous pyelonephritis (XGP) is a rare form of pyelonephritis more commonly seen in females and diabetics. Frequently associated with renal tract calculi, it is often difficult to diagnose, as it can clinically and radiologically mimic other disorders. Most cases are treated with antibiotics and nephrectomy. The aim of our review is to summarise and analyse the current evidence focusing on management. METHODS: A literature search was conducted to identify papers relating to xanthogranulomatous pyelonephritis in adults. Studies containing ten or more patients with XGP were included for descriptive analysis, and a meta-analyses of cohort studies conducted comparing open and minimally invasive nephrectomy undertaken. Other papers were included for narrative review. RESULTS: 52 studies were identified, 20 were included for narrative review and 32 retrospective observational studies containing 868 patients were included for descriptive analysis. 99.8% of patients underwent nephrectomy, about one-third laparoscopically. The most commonly cultured organisms were Escherichia coli and Proteus mirabilis. 60% of patients, where reported, underwent preoperative drainage. Seven studies containing 211 patients were included for meta-analysis which found that postoperative complications, length of stay and transfusion requirements were all significantly reduced in those who underwent minimally invasive surgery. CONCLUSION: The mainstay management of XGP is antibiotic therapy and nephrectomy. Some studies highlight a role for preoperative upper urinary tract drainage, but evidence supporting this is limited. We present the first meta-analyses examining operative approach for patients undergoing nephrectomy for XGP. Though limited by the data available, our meta-analysis indicates minimally invasive nephrectomy for XGP provides better postoperative outcomes.

Role of Ureteroscopy in Treatment of Upper Tract Urothelial Carcinoma.

PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is uncommon accounting for less than 10% of all urothelial tumours. Ureteroscopic management (URS) is the first line treatment for low-risk disease and has been increasingly utilised due to technological advances and increasing surgical experience. This review looks at patient outcomes relating to URS, emerging technologies and the role of adjuvant intracavitary therapy in the management of UTUC. RECENT FINDINGS: URS has firmly established itself in the management algorithm for UTUC, and a good body of evidence supports its use for low-risk disease, wherein oncological outcomes are comparable to traditional nephroureterectomy (RNU). Larger tumours can now be managed using URS with a lower morbidity than radical surgery, though with higher associated local recurrence rate and risk of progression to RNU, and as a result, patient selection and close surveillance remains key. There is limited evidence for adjuvant intracavitary therapy (Mitomycin C or BCG) in UTUC although the development of novel polymers and biodegradable stents may improve drug delivery to the upper urinary tract. URS has a clearly defined role in low-risk UTUC, and its use in larger tumours appears to be appropriate in a selected cohort of patients. The efficacy of adjuvant intracavitary therapy is as of yet undetermined, though developments in delivery techniques are promising. Likewise further developments of laser technology are anticipated to further expand the role of URS.

Time to Turn on the Blue Lights: A Systematic Review and Meta-analysis of Photodynamic Diagnosis for Bladder Cancer.

CONTEXT: White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer. However, with WL cystoscopy, recurrence following initial TURBT is high, and identification of smaller tumours and carcinoma in situ is poor. Photodynamic diagnosis (PDD) has been developed to improve the detection of bladder. OBJECTIVE: To assess the effect of PDD-guided TURBT compared with WL on recurrence rates (RRs) in non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: A systematic review of the literature from inception to April 2020 using Medline, EMBASE, and CENTRAL was undertaken. Randomised control trials comparing TURBT undertaken with PDD to WL that reported RRs of at least 12 mo were included in the analysis. The primary outcomes were RRs at 12 and 24 mo. The secondary outcomes were reported adverse effects. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of the evidence. EVIDENCE SYNTHESIS: Twelve randomised controlled trials (2288 patients) were included for the meta-analysis. PDD was found to reduce RRs at 12 mo (RR 0.73, confidence interval [CI] 0.60-0.88) and 24 mo (RR 0.75, CI 0.62-0.91). There was an increased risk of recurrence for patients undergoing WL at 12 mo (hazard ratio [HR] 1.14, CI 1.05-1.23) and 24 mo (HR 1.25, CI 1.15-1.35). Two studies reported recurrence data at 60 mo showing statistically significant outcomes in favour of PDD: one showed lower RRs for PDD (49% PDD vs 68% WL), whilst the other showed increased recurrence-free survival (68.2% PDD vs 57.3% WL). Adverse effects appeared to be minimal, though poorly reported. A GRADE analysis showed the evidence to be of moderate certainty overall. CONCLUSIONS: This systematic review found that PDD reduced RRs and improved recurrence-free survival compared with WL in NMIBC over at least 2-yr follow-up. These effects may persist up to 5 yr. Further research in a pragmatic study looking at longer-term outcomes beyond 24 mo will help guide recommendations on clinical adoption. PATIENT SUMMARY: This review suggests that photodynamic diagnosis, compared with white light cystoscopy, improves recurrence-free survival in non-muscle-invasive bladder cancer over at least 2 yr of follow-up. However, confirmatory pragmatic studies with longer-term outcomes are required for its clinical adoption.

Systematic review and meta-analysis of narrow band imaging for non-muscle-invasive bladder cancer.

To assess the effect of narrow band imaging-guided transurethral resection of bladder tumor compared with white light on recurrence rates in non-muscle-invasive bladder cancer. A systematic review of the literature from inception to November 2020 using Medline, EMBASE and CENTRAL was undertaken. Randomized controlled trials comparing transurethral resection of bladder tumor undertaken with narrow band imaging with those undertaken with white light that reported recurrence rates of at least 12 months were included in the analysis. Primary outcomes were recurrence rates at 12 and 24 months. Secondary outcomes were reported adverse effects. A total of 387 abstracts were screened, of which 14 full text identified and three studies included in the meta-analysis (921 patients). Meta-analysis did not show a statistically significant benefit to narrow band imaging at 12 months; risk ratio 0.75 (95% confidence interval 0.50-1.14, P = 0.18, I2  = 61%). No included studies provided recurrence data beyond 12 months. Adverse effects were reported in one study and no significant difference of complication rate was observed between the two groups. Risk of bias was assessed to be generally low, and grading of recommendations assessment development and evaluations were of high certainty. This meta-analysis of randomized controlled trials shows no difference in recurrence rates using narrow band imaging, although a trend in its favor was identified. Limitations include the varied reporting and administration of adjuvant therapies. Further well-designed trials are required to examine the benefit of this technology.