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Background Despite years of slow progress, muscle invasive bladder cancer (MIBC) is finally entering the era of molecularly guided targeted therapy. However, tumor heterogeneity is high in MIBC and may impact treatment response and resistance. The objective of this review is to dissect recent insights into inter- and intratumor heterogeneity (ITH) in MIBC, with emphasis on the clinical implications of this heterogeneity for biomarker-driven strategies and the development of new therapies. Methods A nonsystematic review was performed in PubMed and EMBASE using the terms “tumor heterogeneity” and “bladder cancer.” Results Intertumor heterogeneity, as reflected by different clinical phenotypes in different patients, has been partially explained with next generation sequencing and other molecular profiling technologies. RNA-based molecular subtyping, for example, provides a classification of MIBC into distinct categories that can be used for further molecular analysis, biomarker discovery, risk stratification, and treatment selection. Molecular subtyping and specific genomic alterations, especially in DNA damage repair genes, may help explain why some patients respond better to systemic chemotherapy and immunotherapy. Conversely, spatial and temporal ITH threaten to confound attempts to target specific molecular lesions since not all tumor cells within a patient may carry the relevant lesion. Improved understanding and management of ITH is required for the most effective use of biomarker-driven targeted therapies. Conclusion Strategies to assess and overcome intertumor and ITH in MIBC will be critical steps toward realizing the objectives of precision oncology. Novel techniques such as analysis of circulating tumor DNA and single cell sequencing are likely to revolutionize our understanding of tumor heterogeneity.

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.

INTRODUCTION AND OBJECTIVE:Renal biopsy requires adequate tissue sampling to aid in the investigation of renal masses. The contemporary rate of non-diagnostic renal biopsy ranges from 15-18%, thoug...

Background: Haematuria often requires investigation with an imaging test and flexible cystoscopy to rule out urinary tract cancers. With a reduction in diagnostic services due to the COVID-19 pandemic there is a risk of compromise in the care of patients referred with haematuria. We aimed to provide a pragmatic strategy that optimises the use of scarce resources by reducing patient visits to hospital and allocating the appropriate diagnostic tests according to risk of bladder cancer. Methods: The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of newly suspected urinary tract cancer. Patients underwent cystoscopy, imaging tests, urine cytology and transurethral resection of bladder tumour (TURBT), where indicated. We developed strategies using combinations of imaging and cytology as triage tests to flexible cystoscopy. These strategies aimed to maximise cancer detection within a pragmatic pathway in a resource-limited environment. Findings: 8112 patients (74 4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70 7%) patients had visible haematuria (VH) and 2375 (29 3%) had non-visible haematuria (NVH). Amongst all patients, 1474 (18 2%) had bladder cancer;1333 (23 2%) in VH group and 141 (5 94%) in NVH group. Diagnostic test performance was used to determine optimal age cut-offs for each proposed strategy. We recommended proceeding directly to TURBT for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients (threshold of 60-years-old with VH, or 70-years-old with NVH) to capture high risk bladder cancer. Interpretation: We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

Introduction: Postoperative ileus (POI) is a common complication of radical cystectomy (RC), occurring in 1.6–23.5% of cases. It is defined heterogeneously in the literature. POI increases hospital length of stay and postoperative morbidity. Factors such as age, epidural use, length of procedure, and blood loss may impact POI. In this study, we aimed to evaluate risk factors that contribute to POI in a cohort of patients managed with a comprehensive Enhanced Recovery After Surgery (ERAS) protocol. Methods: A retrospective review of consecutive patients who underwent RC from March 2015 to December 2016 at Vancouver General Hospital was performed. POI was defined a priori as insertion of nasogastric tube for nausea or vomiting, or failure to advance to a solid diet by the seventh postoperative day. To illustrate heterogeneity in previous studies, we also evaluated POI using other previously reported definitions in the RC literature. The influence of potential risk factors for POI, including patient comorbidities, American Society of Anesthesiologists score, gender, age, prior abdominal surgery or radiation, length of operation, diversion type, extent of lymph node dissection, removal date of analgesic catheter, blood loss, and fluid administration volume was analyzed. Results: Thirty-six (27%) of 136 patients developed POI. Using other previously reported definitions for POI, the incidence ranged from

Introduction: Prostate incidentalomas are prostatic lesions suspicious for cancer discovered by imaging patients without a known history of prostatic cancer (CaP) for other reasons. 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET) is used to diagnose, stage and assess response to treatment for numerous cancers, but it is not routinely used for CaP. We aimed to determine the rate of detection of prostate incidentalomas in patients undergoing FDG PET and to evaluate the natural history of these lesions. Methods: A retrospective review was conducted of all FDG PET scans performed between 2005 and 2017 at a single institution. Patients were selected who had prostatic uptake without a history of prostate cancer. Clinical data were collected from electronic medical records to determine how the prostate incidentalomas were further evaluated and define the rate of malignancy. Results: A prostate incidentaloma was identified in 309 (1.0%) of 31 019 FDG PET scans performed on men. A prostate-specific antigen (PSA) test was obtained in 40.1% of patients within six months of prostate incidentaloma detection. Six patients underwent a multiparametric magnetic resonance imaging (MRI) of the prostate, which identified CaP in one case. Overall, CaP was diagnosed in 33 cases, representing 10.7% of the prostate incidentalomas and 0.1% of the scanned patients. CaP was intermediate- or high-risk in 27 (8.7%) of the prostate incidentalomas. Conclusions: Incidental lesions detected in the prostate by FDG PET may represent clinically significant CaP. Referral to a urologist for further evaluation should be considered if the patient is otherwise in reasonable health.

Radical cystectomy (RC) is a challenging procedure with significant morbidity, though remains the standard of care treatment for many patients with bladder cancer. There has been debate regarding the utility of universal risk calculators to aid in point-of-care prediction of complications in individual patients preoperatively. We retrospectively evaluated the predictive value of the ACS NSQIP universal surgical risk calculator in our patients who underwent RC. A prospective cohort of patients undergoing RC was retrospectively reviewed between October 2014 and August 2017. Only patients who underwent a RC for genitourinary cancer without significant deviation from NSQIP surgery codes 51590, 51595, and 51596 (n = 29) were included. The accuracy of the risk calculator was assessed by ROC AUC and Brier scores for both NSQIP and Clavien–Dindo defined complications. Additionally, each NSQIP risk factor was individually assessed for association with postoperative complications. 223 patients who underwent open or robotic RC (n = 18) were included for analysis. Determined by AUC C-stat and Brier scores, prediction was good for cardiac complications (0.80 and 0.021), fair for pneumonia (0.75 and 0.017), poor for UTI (0.64 and 0.078), 30-day mortality (0.62 and 0.013), any complication (0.60 and 0.19) and serious complication (0.60 and 0.17). There was a significant discordance between the rate of NSQIP predicted vs. Clavien–Dindo observed any and serious complications: 28.8% vs. 67.3%, and 25.3% vs. 11.7%, respectively. The NSQIP universal surgical risk calculator did not perform with enough accuracy to consider adoption into clinical practice.

As our molecular understanding of bladder cancer continues to advance, more and more novel agents are entering clinical trials across the spectrum of bladder cancer stages. The clinical trial activity for non-muscle invasive bladder cancer (NMIBC) has been boosted further by the evolution of specific disease states that set more uniform inclusion criteria for clinical trial design. Here, we aimed to review the current clinical trials landscape in non-muscle invasive bladder cancer with respect to these disease states. Most active clinical trials focus on high-risk NMIBC in either the BCG-naive or BCG-unresponsive setting. Strict criteria to define the disease state and a clear pathway to drug registration have encouraged trials for patients with BCG-unresponsive NMIBC. The most promising potential breakthroughs for BCG-naive patients include alternative BCG strains, immune-priming with intradermal BCG vaccination, and systemic immune checkpoint blockade. The latter therapy is also being actively investigated in multiple trials in BCG-unresponsive NMIBC, along with novel viral agents such as INSTILADRIN (nadofaragene firadenovec) and targeted agents such as oportuzumab monatox. After many years of relative stagnation, multiple new therapies currently under investigation in well-designed clinical trials appear poised for routine clinical implementation in the near future. These therapies should dramatically improve the outcome of patients with NMIBC. We can look forward to the challenges of biomarker-driven drug selection, optimal drug sequencing, and rational combination therapies.

Purpose of review A bladder-preserving approach for high-grade nonmuscle invasive bladder cancer that has invaded the lamina propria (T1HG) may result in increased recurrence, progression, and even death from bladder cancer in some patients. Initial radical cystectomy does have increased cancer-specific survival (CSS), but represents significant overtreatment for many patients. An evidence-based, risk-stratified approach is required to select patients for immediate radical cystectomy in order to improve CSS. Recent findings A restaging transurethral resection aids in optimal staging and treatment of T1HG. Intravesical Bacillus Calmette-Guerin induction followed by 3 years of maintenance is the standard adjuvant management. However, when very high-risk (hydronephrosis, abnormal bimanual examination, variant histology, lymphovascular invasion, or residual disease on re-resection, and Bacillus Calmette-Guerin failure or early recurrence) or multiple high-risk factors (concomitant CIS, size >3 cm, multifocality, unfavorable tumor location, extensive lamina propria invasion, and elderly) are present, the risk of progression often outweighs the risk associated with radical cystectomy. In these cases, an immediate radical cystectomy likely provides an improved opportunity for cure compared to a bladder-preserving strategy. Summary In order to increase the CSS of patients diagnosed with T1HG bladder cancer, an aggressive approach may benefit those with increased risk of progression.

Horseshoe kidney (HSK) is a benign malformation characterized by three anatomic abnormalities: ectopia, malrotation, and vascular changes.1 Renal cell carcinoma (RCC) comprises approximately 53.8% of HSK malignancies. The incidence of RCC within HSK is predicted to equal that within the general population, approximately 5.2/100 000 individuals.2-4 Surgical resection of these tumors has been described in the literature. Evidence is mounting that partial nephrectomy, rather than radical nephrectomy, and minimally invasive techniques for T3a RCC is safe and attains equivalent oncologic outcomes.5,6 Review of the literature reveals no case reports of laparoscopic partial nephrectomy for T3a RCC, and therefore, this is the first report of a laparoscopic partial nephrectomy of T3a RCC HSK with renal vein tumour thrombus.