Developing a Diagnostic Multivariable Prediction Model for Urinary Tract Cancer in Patients Referred with Haematuria: Results from the IDENTIFY Collaborative Study.

BACKGROUND: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. OBJECTIVE: To develop a prediction model for urinary tract cancer in patients referred with haematuria. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. RESULTS AND LIMITATIONS: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. CONCLUSIONS: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. PATIENT SUMMARY: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.

A Systematic Review and Meta-analysis of Adjuncts to Minimally Invasive Treatment of Urethral Stricture in Men.

CONTEXT: Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates. OBJECTIVE: To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD. EVIDENCE ACQUISITION: A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist. EVIDENCE SYNTHESIS: A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p <  0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p <  0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p =  0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen. CONCLUSIONS: Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence. PATIENT SUMMARY: We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

A Systematic Review of Surgical interventions for the Treatment of Bladder Pain Syndrome/Interstitial Cystitis.

CONTEXT: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a poorly understood chronic debilitating condition. Surgery is reserved for severe refractory cases; however, there is no consensus on patient selection or optimal approach. OBJECTIVE: To evaluate the evidence relating to the safety and efficacy of surgical interventions for treating BPS/IC. EVIDENCE ACQUISITION: PubMed and Scopus databases were searched for original studies, using keywords "cystectomy", "interstitial cystitis", and "bladder pain syndrome". Articles were reviewed and screened by three independent reviewers. EVIDENCE SYNTHESIS: A total of 450 patients were identified from 20 eligible studies: mean age was 54.5 yr and 90.2% were female. The median duration of symptoms preoperatively was 60 mo (range 9-84), with a mean follow-up of 45.5 mo. A total of 448 patients underwent surgery: subtotal cystectomy with cystoplasty (48.6%), cystectomy and orthotopic neobladder (21.9%), cystectomy and ileal conduit (11.2%), and urinary diversion only (18.3%). Symptomatic improvement occurred in 77.2%, with higher rates in the total cystectomy and orthotopic neobladder group. Thirty-one patients (6.9%) required secondary total cystectomy and/or ileal conduit diversion; 48.4% subsequently improved. Seventeen studies reported 102 complications overall (26.5%). Overall mortality was 1.3%. CONCLUSIONS: Overall surgical intervention is associated with a 23% risk of failure to improve symptoms. Higher rates of improvement were reported in patients with total cystectomy. Interpretation should be guarded given the small patient number, multiple centres, and variable outcome measurements. There is a need for prospective randomised studies to answer questions regarding patient selection and optimal surgical approach. PATIENT SUMMARY: In this review, we looked at the outcomes of surgery for treatment-refractory bladder pain syndrome/interstitial cystitis. We found overall symptom improvement in 77.2% of patients with a complication rate of 26.5%. However, there remains a need for further studies of higher quality to identify patients who will have symptom improvement and the best surgical option.

What is the Role of Surgery in Bladder Pain Syndrome?

The role of surgery in the management of bladder pain syndrome is unclear; particularly the optimum surgical approach. Treatment refractory patients should be managed in a multi-disciplinary setting including psychological support. Further prospective studies using validated assessments and clear diagnostic criteria would be useful to guide patient selection.