Rachael Sarpong

Who Should Be Investigated for Haematuria? Results of a Contemporary Prospective Observational Study of 3556 Patients

There remains a lack of consensus among guideline relating to which patients require investigation for haematuria. We determined the incidence of urinary tract cancer in a prospective observational study of 3556 patients referred for investigation of haematuria across 40 hospitals between March 2016 and June 2017 (DETECT 1; ClinicalTrials.gov: NCT02676180) and the appropriateness of age at presentation in cases with visible (VH) and nonvisible (NVH) haematuria. The overall incidence of urinary tract cancer was 10.0% (bladder cancer 8.0%, renal parenchymal cancer 1.0%, upper tract transitional cell carcinoma 0.7%, and prostate cancer 0.3%). Patients with VH were more likely to have a diagnosis of urinary tract cancer compared with NVH patients (13.8% vs 3.1%). Older patients, male gender, and smoking history were independently associated with urinary tract cancer diagnosis. Of bladder cancers diagnosed following NVH, 59.4% were high-risk cancers, with 31.3% being muscle invasive. The incidence of cancer in VH patients <45 yr of age was 3.5% (n=7) and 1.0% (n=4) in NVH patients <60 yr old. Our results suggest that patients with VH should be investigated regardless of age. Although the risk of urinary tract cancer in NVH patients is low, clinically significant cancers are detected below the age threshold for referral for investigation.nnnPATIENT SUMMARYnThis study highlights the requirement to investigate all patients with visible blood in the urine and an age threshold of ≥60 yr, as recommended in some guidelines, as the investigation of nonvisible blood in the urine will miss a significant number of urinary tract cancers. Patient preference is important, and evidence that patients are willing to submit to investigation should be considered in reaching a consensus recommendation for the investigation of haematuria. International consensus to guide that patients will benefit from investigation should be developed.

DETECT I & DETECT II: a study protocol for a prospective multicentre observational study to validate the UroMark assay for the detection of bladder cancer from urinary cells

BackgroundHaematuria is a common finding in general practice which requires visual inspection of the bladder by cystoscopy as well as upper tract imaging. In addition, patients with non-muscle invasive bladder cancer (NMIBC) often require surveillance cystoscopy as often as three monthly depending on disease risk. However, cystoscopy is an invasive procedure which is uncomfortable, requires hospital attendance and is associated with a risk of urinary tract infection. We have developed the UroMark assay, which can detect 150 methylation specific alteration specific to bladder cancer using DNA from urinary sediment cells.MethodsDETECT I and DETECT II are two multi-centre prospective observational studies designed to conduct a robust validation of the UroMark assay. DETECT I will recruit patients having diagnostic investigations for haematuria to determine the negative predictive value of the UroMark to rule out the presence of bladder cancer. DETECT II will recruit patients with new or recurrent bladder cancer to determine the sensitivity of the UroMark in detecting low, intermediate and high grade bladder cancer. NMIBC patients in DETECT II will be followed up with three monthly urine sample collection for 24xa0months while having surveillance cystoscopy. DETECT II will include a qualitative analysis of semi-structured interviews to explore patients’ experience of being diagnosed with bladder cancer and having cystoscopy and a urinary test for bladder cancer surveillance. Results of the UroMark will be compared to cystoscopy findings and histopathological results in patients with bladder cancer.DiscussionA sensitive and specific urinary biomarker will revolutionise the haematuria diagnostic pathway and surveillance strategies for NMIBC patients. None of the six approved US Food and Drug Administration urinary test are recommended as a standalone test. The UroMark assay is based on next generation sequencing technology which interrogates 150 loci and represents a step change compared to other biomarker panels. This enhances the sensitivity of the test and by using a random forest classifier approach, where the UroMark results are derived from a cut off generated from known outcomes of previous samples, addresses many shortcomings of previous assays.Trial registrationBoth trails are registered on clinicaltrials.gov. DETECT I: NCT02676180 (18th December 2015). DETECT II: NCT02781428 (11th May 2016).

Can Renal and Bladder Ultrasound Replace Computerized Tomography Urogram in Patients Investigated for Microscopic Hematuria

Purpose Computerized tomography urogram is recommended when investigating patients with hematuria. We determined the incidence of urinary tract cancer and compared the diagnostic accuracy of computerized tomography urogram to that of renal and bladder ultrasound for identifying urinary tract cancer. Materials and Methods The DETECT (Detecting Bladder Cancer Using the UroMark Test) I study is a prospective observational study recruiting patients 18 years old or older following presentation with macroscopic or microscopic hematuria at a total of 40 hospitals. All patients underwent cystoscopy and upper tract imaging comprising computerized tomography urogram and/or renal and bladder ultrasound. Results A total of 3,556 patients with a median age of 68 years were recruited in this study, of whom 2,166 underwent renal and bladder ultrasound, and 1,692 underwent computerized tomography urogram in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer was 11.0%, 1.4% and 0.8%, respectively, in macroscopic hematuria cases. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and upper tract urothelial cancer, respectively. The sensitivity and negative predictive value of renal and bladder ultrasound to detect renal cancer were 85.7% and 99.9% but they were 14.3% and 99.7%, respectively, to detect upper tract urothelial cancer. Renal and bladder ultrasound was poor at identifying renal calculi. Renal and bladder ultrasound sensitivity was lower than that of computerized tomography urogram to detect bladder cancer (each less than 85%). Cystoscopy had 98.3% specificity and 83.9% positive predictive value. Conclusions Computerized tomography urogram can be safely replaced by renal and bladder ultrasound in patients who have microscopic hematuria. The incidence of upper tract urothelial cancer is 0.8% in patients with macroscopic hematuria and computerized tomography urogram is recommended. Patients with suspected renal calculi require noncontrast renal tract computerized tomography. Imaging cannot replace cystoscopy to diagnose bladder cancer.

Does urinary cytology have a role in haematuria investigations

To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria.

Multidomain Quantitative Recovery Following Radical Cystectomy for Patients Within the Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion Versus Open Radical Cystectomy Randomised Controlled Trial: The First 30 Patients

Many patients develop complications after radical cystectomy (RC) [1]. Reductions in morbidity have occurred through centralisation and technical improvements [2], and perhaps through robot-assisted RC (RARC). Whilst RARC is gaining popularity, there are concerns about oncological safety [3] and extracorporeal reconstruction [4], and randomised controlled trials (RCTs) find little difference [5]. We are conducting a prospective RCT comparing open RC and RARC with mandated intracorporeal reconstruction (Robot-assisted Radical Cystectomy with intracorporeal urinary diversion versus Open Radical Cystectomy [iROC] trial) [6].

Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study

Introduction Bladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery. Methods and analysis iROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size. Ethics and dissemination The study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups. Trial registration numbers ISRCTN13680280 and NCT03049410.