Impact of COVID-19 on the management and outcomes of ureteric stones in the UK: a multicentre retrospective study.

OBJECTIVES: To determine if management of ureteric stones in the UK changed during the coronavirus disease 2019 (COVID-19) pandemic and whether this affected patient outcomes. PATIENTS AND METHODS: We conducted a multicentre retrospective study of adults with computed tomography-confirmed ureteric stone disease at 39 UK hospitals during a pre-pandemic period (23/3/2019-22/6/2019) and a period during the pandemic (the 3-month period after the first severe acute respiratory syndrome coronavirus-2 case at individual sites). The primary outcome was success of primary treatment modality, defined as no further treatment required for the index ureteric stone. Our study protocol was published prior to data collection. RESULTS: A total of 3735 patients were included (pre-pandemic 1956 patients; pandemic 1779 patients). Stone size was similar between groups (P > 0.05). During the pandemic, patients had lower hospital admission rates (pre-pandemic 54.0% vs pandemic 46.5%, P < 0.001), shorter mean length of stay (4.1 vs 3.3 days, P = 0.02), and higher rates of use of medical expulsive therapy (17.4% vs 25.4%, P < 0.001). In patients who received interventional management (pre-pandemic 787 vs pandemic 685), rates of extracorporeal shockwave lithotripsy (22.7% vs 34.1%, P < 0.001) and nephrostomy were higher (7.1% vs 10.5%, P = 0.03); and rates of ureteroscopy (57.2% vs 47.5%, P < 0.001), stent insertion (68.4% vs 54.6%, P < 0.001), and general anaesthetic (92.2% vs 76.2%, P < 0.001) were lower. There was no difference in success of primary treatment modality between patient cohorts (pre-pandemic 73.8% vs pandemic 76.1%, P = 0.11), nor when patients were stratified by treatment modality or stone size. Rates of operative complications, 30-day mortality, and re-admission and renal function at 6 months did not differ between the data collection periods. CONCLUSIONS: During the COVID-19 pandemic, there were lower admission rates and fewer invasive procedures performed. Despite this, there were no differences in treatment success or outcomes. Our findings indicate that clinicians can safely adopt management strategies developed during the pandemic to treat more patients conservatively and in the community.

Bioengineering solutions for ureteric disorders: clinical need, challenges and opportunities.

OBJECTIVES: To summarise the causes of ureteric damage and the current standard of care, discussing the risks and benefits of available therapeutic options. We then focus on the current and future solutions that can be provided by ureteric bioengineering and provide a description of the ideal characteristics of a bioengineered product. METHODS: We performed a literature search in February 2021 in: Google Scholar, Medline, and Web of Science. Three searches were conducted, investigating: (a) the epidemiology of ureteric pathology, (b) the current standard of care, and (c) the state of the art in ureteric bioengineering. RESULTS: The most-common causes of ureteric damage are iatrogenic injury and external trauma. Current approaches to treatment include stent placement or surgical reconstruction. Reconstruction can be done using either urological tissue or segments of the gastrointestinal tract. Limitations include scarring, strictures, and infections. Several bioengineered alternatives have been explored in animal studies, with variations in the choice of scaffold material, cellular seeding populations, and pre-implantation processing. Natural grafts and hybrid material appear to be associated with superior outcomes. Furthermore, seeding of the scaffold material with stem cells or differentiated urothelial cells allows for better function compared to acellular scaffolds. Some studies have attempted to pre-implant the graft in the omentum prior to reconstruction, but this has yet to prove any definitive benefits. CONCLUSION: There is an unmet clinical need for safer and more effective treatment for ureteric injuries. Urological bioengineering is a promising solution in preclinical studies. However, substantial scientific, logistic, and economic challenges must be addressed to harness its transformative potential in improving outcomes.

Diagnostic accuracy of biparametric versus multiparametric prostate MRI: assessment of contrast benefit in clinical practice.

PURPOSE: To assess the added value of dynamic contrast-enhanced (DCE) in prostate MR in clinical practice. METHODS: Two hundred sixty-four patients underwent prostate MRI, with T2 and DWI sequences initially interpreted, prior to full multiparametric magnetic resonance imaging (mpMRI) interpretation using a Likert 1-5 scale. A prospective opinion was given on likely benefit of contrast prior to review of the DCE sequence, and retrospectively following full mpMRI review. The final histology result following targeted and/or systematic biopsy of the prostate was used for outcome purposes. RESULTS: Biparametric magnetic resonance imaging (bpMRI) and mpMRI were assigned the same score in 86% of cases; when dichotomising to a negative or positive MRI (Likert score ≥ 3), concordance increased to 92.8%. At Likert score ≥ 3 bpMRI detected 89.9% of all cancers and 93.5% clinically significant prostate cancers (csPCa) and mpMRI 90.7% and 94.6%, respectively. mpMRI had fewer false positives than bpMRI (11.4% vs 18.9%) and a lower Likert 3 rate (8.3% vs 17%), conferring higher specificity (74% vs 67%), but similar sensitivity (95% versus 94%) and ROC-AUC (90% vs 89%). At a positive MRI threshold of Likert ≥ 4, mpMRI had a higher sensitivity than bpMRI (89% versus 80%) and detected more csPCa (89.2% versus 79.6%). DCE was prospectively considered of potential benefit in 27.3%, but readers would only recall 11% of patients for DCE sequences, mainly to assess score 3 peripheral zone lesions. Following full mpMRI review, DCE was considered helpful in 28.4% of cases; in 23/75 (30.6%) of these cases this only became apparent after reviewing the sequence, reasons included increased confidence, presence of "safety-net" lesions or inflammatory lesions. CONCLUSION: BpMRI has equivalent cancer detection rates to mpMRI; however, mpMRI had fewer Likert 3 call rates and increased specificity and was subjectively considered of benefit by readers in 28.4% of cases. KEY POINTS: • bpMRI has similar cancer detection rates to the full mpMRI protocol at a positive MRI threshold of Likert 3. • mpMRI had fewer intermediate category 3 calls (8.3%) than bpMRI (17%) and fewer false positives than bpMRI (11.4% vs 18.9%), conferring higher specificity (74% vs 67%). • Readers considered DCE beneficial in 28.4% of cases, but in a relatively high number (30.6%) this only became apparent after reviewing the sequence.

Progression and treatment rates using an active surveillance protocol incorporating image-guided baseline biopsies and multiparametric magnetic resonance imaging monitoring for men with favourable-risk prostate cancer.

OBJECTIVE: To assess early outcomes since the introduction of an active surveillance (AS) protocol incorporating multiparametric magnetic resonance imaging (mpMRI)-guided baseline biopsies and image-based surveillance. PATIENTS AND METHODS: A new AS protocol mandating image-guided baseline biopsies, annual mpMRI and 3-monthly prostate-specific antigen (PSA) testing, but which retained protocol re-biopsies, was tested. Pathological progression, treatment conversion and triggers for non-protocol biopsy were recorded prospectively. RESULTS: Data from 157 men enrolled in the AS protocol (median age 64 years, PSA 6.8 ng/mL, follow-up 39 months) were interrogated. A total of 12 men (7.6%) left the AS programme by choice. Of the 145 men who remained, 104 had re-biopsies either triggered by a rise in PSA level, change in mpMRI findings or by protocol. Overall, 23 men (15.9%) experienced disease progression; pathological changes were observed in 20 men and changes in imaging results were observed in three men. Of these 23 men, 17 switched to treatment, giving a conversion rate of 11.7% (<4% per year). Of the 20 men with pathological progression, this was detected in four of them after a PSA increase triggered a re-biopsy, while in 10 men progression was detected after an mpMRI change. Progression was detected in six men, however, solely after a protocol re-biopsy without prior PSA or mpMRI changes. Using PSA and mpMRI changes alone to detect progression was found to have a sensitivity and specificity of 70.0% and 81.7%, respectively. CONCLUSION: Our AS protocol, with thorough baseline assessment and imaging-based surveillance, showed low rates of progression and treatment conversion. Changes in mpMRI findings were the principle trigger for detecting progression by imaging alone or pathologically; however, per protocol re-biopsy still detected a significant number of pathological progressions without mpMRI or PSA changes.

Evolution of repeat prostate biopsy strategies incorporating transperineal and MRI-TRUS fusion techniques.

PURPOSE: To test the hypothesis that MRI-TRUS fusion technique can increase the detection rate of prostate cancer (PC) in patients with previously negative biopsy. METHODS: Patient records of men with persisting suspicion for PC after previous negative biopsy having undergone either extensive transrectal prostate biopsies (MD Anderson protocol; MDA), transperineal saturation (STP) or magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion transperineal biopsies (MTTP) in three consecutive time intervals were reviewed retrospectively. The respective approach was the standard for the above indication at these episodes. In Cambridge, 70 patients underwent MDA biopsies, 75 STP underwent biopsies and 74 patients underwent MTTP biopsies. In total, 164 MTTP patients with the same indication from Heidelberg were analysed as reference standard. In total, 383 men were included into analysis. Low-grade PC was defined as Gleason score 7 (3 + 4) or lower. RESULTS: Even though MTTP patients had significantly larger prostates, the overall cancer detection rate for PC was the highest in MTTP (24.2 % MDA, 41.3 % STP, 44.5 % MTTP, p = 0.027, Kruskal-Wallis test). The detection rate for clinically relevant high-grade PC was highest in MTTP; however, this did not reach statistical significance compared with MDA (23.5 % MDA, 12.9 % STP, 27.2 % MTTP, p = 0.25, Fischer's exact test). Comparing MTTP between Cambridge and Heidelberg, detection rates did not differ significantly (44.5 vs. 48 %, p = 0.58). There was a higher detection rate of high-grade cancer in Heidelberg. (36.3 vs. 27.2 %, p = 0.04). CONCLUSION: Patients whom are considered for repeat biopsies may benefit from undergoing MRI-targeted TRUS fusion technique due to higher cancer detection rate of significant PC.

Diagnostic value of the abnormal digital rectal examination in the modern MRI-based prostate cancer diagnostic pathway.

Objective: Currently the National Institute for Health and Care Excellence (NICE) recommends an abnormal digital rectal examination (DRE) as a standalone referral criterion for suspected prostate cancer. Unlike referrals for a raised prostate-specific antigen (PSA) which are triaged directly to magnetic resonance imaging (MRI), an abnormal DRE requires re-examination in a secondary clinic first. Here, we investigated the ongoing value of the abnormal DRE as a referral criterion. Methods: This study is a retrospective review of patients referred to secondary care for suspected prostate cancer based on an abnormal DRE over a 15-month period at a single UK hospital (n = 158). Age, PSA, primary and repeat DRE findings and eventual diagnosis were collated. Results: A concurrent raised PSA was present in 65/158 (41%). Concordance between primary and secondary care DRE was only 72/158 (46%). The overall and significant cancer detection rate was 26/158 (16%) and 22/158 (14%), respectively. Among men with a concurrent raised PSA, 19/65 (29%) had significant cancer found, whereas with an abnormal primary care DRE and normal PSA (n = 93), only 3/93 (3%) had a significant cancer. Mandating a PSA before referral for an abnormal DRE would have redirected 65/158 (41%) of men to MRI first, negating the need for a repeat DRE (p < 0.0001). This finding was recapitulated in a second prospective validation cohort (n = 30) with 9/30 (30%) redirected to MRI first. Conclusions: This is one of the first studies to investigate the value of the DRE in contemporary practice. We propose that PSA is used to triage men with an abnormal DRE to MRI without needing a repeat DRE. If the PSA is normal, the diagnostic yield is low but may still warrant a repeat DRE to assess the need for further investigations. Additional multicentre studies are required to further validate our findings. Level of evidence: 4.

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995-2006.

OBJECTIVE: • To examine the use of radiotherapy and radical surgery for bladder urothelial cell carcinoma (UCC) before, during and after national initiatives for reorganization of uro-oncology services. PATIENTS AND METHODS: • Population-based data (1995-2006) from a cancer registry with stable coding practices were analysed. • Bladder UCC was defined using relevant International Classification of Disease site and morphology codes. • Time trends in the use of radiotherapy and radical surgery, and other predictors of their use were examined. RESULTS: • Of 4639 bladder UCC patients aged ≥40 years (76% men), stage information was available for 4303 (93%). • Morphology and stage case mix remained stable during the study period. • Radiotherapy use decreased significantly (from 31% in 1995-1998 to 22% in 2003-2006, P < 0.001) among patients of any stage, whilst radical surgery use increased significantly (from 8 to 13%, P < 0.001), particularly among stage II-IV patients. • The proportion of patients treated by both radiotherapy and surgery also decreased notably (from 4.0 to 1.1%). • Women were significantly more likely to present in stages II-IV [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.06-1.40, P = 0.005], and less likely to be treated with radiotherapy (OR = 0.84, 95% CI: 0.72-0.99, P = 0.036). CONCLUSIONS: • Use of radical surgery in UCC invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management. Sociodemographic variation in treatment was limited to lower use of radiotherapy in women. • Further research should encompass treatment timeliness and other aspects of care quality, as well as exploring potential differences in endoscopic treatments for disease not invading bladder muscle.

Percutaneous Cystolitholapaxy Using the LithoClast Trilogy for Multiple Bladder Stones.

Background: Multiple large bladder calculi are traditionally managed through open cystolithotomy or transurethrally in patients who have an open bladder neck. Open procedures are technically challenging in patients who may have had multiple previous open surgeries, and may be associated with significant morbidity in patients with a high comorbid burden. Therefore, a percutaneous approach to such stones has been used especially when there is a closed bladder neck, and has been shown to be effective. There are a number of available devices for breaking stones in these approaches, the newest of which is the LithoClast Trilogy™ (EMS, Nyon, Switzerland) device, a probe that provides ultrasonic and mechanical calculi fragmentation and suction in a single instrument. Case Presentation: We describe the first reported case of percutaneous cystolitholapaxy using the LithoClast Trilogy device in a 41-year-old woman with spina bifida, and multiple large bladder calculi with a history of ileocystoplasty and Mitrofanoff formation, and a bladder neck closure for neuropathic bladder. The calculi measured 31 and 25 mm, and had a volume of 19.6 and 7.9 cm3 and average HU of 408 and 462, respectively. The calculi were composed of 37% calcium phosphate and 63% magnesium ammonium phosphate. Conclusion: We demonstrate that this approach can be used as a viable alternative to open surgery, which is of particular importance for complex patients who have undergone multiple previous open operations, and who may have a high comorbid burden.

Comparison of Likert and PI-RADS version 2 MRI scoring systems for the detection of clinically significant prostate cancer.

OBJECTIVE: To compare the performance of Likert and Prostate Imaging-Reporting and Data System (PI-RADS) multiparametric (mp) MRI scoring systems for detecting clinically significant prostate cancer (csPCa). METHODS: 199 biopsy-naïve males undergoing prostate mpMRI were prospectively scored with Likert and PI-RADS systems by four experienced radiologists. A binary cut-off (threshold score ≥3) was used to analyze histological results by three groups: negative, insignificant disease (Gleason 3 + 3; iPCa), and csPCa (Gleason ≥3 +4). Lesion-level results and prostate zonal location were also compared. RESULTS: 129/199 (64.8%) males underwent biopsy, 96 with Likert or PI-RADS score ≥3, and 21 with negative MRI. A further 12 patients were biopsied during follow-up (mean 507 days). Prostate cancer was diagnosed in 87/199 (43.7%) patients, 65 with (33.6%) csPCa. 30/92 (32.6%) patients with negative MRI were biopsied, with an NPV of 83.3% for cancer and 86.7% for csPCa. Likert and PI-RADS score differences were observed in 92 patients (46.2%), but only for 16 patients (8%) at threshold score ≥3. Likert scoring had higher specificity than PI-RADS (0.77 vs 0.66), higher area under the curve (0.92 vs 0.87, p = 0.002) and higher PPV (0.66 vs 0.58); NPV and sensitivity were the same. Likert had more five score results (58%) compared to PI-RADS (36%), but with similar csCPa detection (81.0 and 80.6% respectively). Likert demonstrated lower proportion of false positive in the predominately AFMS-involving lesions. CONCLUSION: Likert and PI-RADS systems both demonstrate high cancer detection rates. Likert scoring had a higher AUC with moderately higher specificity and lower positive call rate and could potentially help to reduce the number of unnecessary biopsies performed. ADVANCES IN KNOWLEDGE: This paper illustrates that the Likert scoring system has potential to help urologists reduce the number of prostate biopsies performed.

Upper Tract Urothelial Carcinoma Grade Prediction Based on the Ureteroscopic Appearance: Caution Should be Taken.

OBJECTIVES: To investigate the diagnostic accuracy, inter-rater and intrarater agreement of grade predictions based on the visual appearance of papillary upper tract urothelial carcinoma (UTUC) during digital ureteroscopy. METHODS: Nine urologists predicted the histopathologic grade of 64 papillary UTUC (low-grade vs high-grade) by assessing the visual appearance of the tumors in videos from digital ureteroscopy. The diagnostic accuracy was estimated by comparing the grade predictions with the histopathology from colocalized biopsies. Inter-rater agreement was assessed by pairwise inter-rater percentage agreement and Fleiss Kappa analysis. The videos were rated in a random order again 30 days after the first assessment to evaluate the intrarater percentage agreement. RESULTS: Low-grade tumors were predicted correctly in 37%-85% of the cases with a median concordance of 59% for questionnaire 1 and 66% for questionnaire 2. High-grade tumors were predicted correctly in 26%-91% of the cases with a median concordance of 52% and 61% for each questionnaire. The median pairwise inter-rater percentage agreement was 66% for both questionnaires with a Fleiss Kappa of 0.29 and 0.38, respectively. The median intrarater percentage agreement was 81%. CONCLUSION: The histopathologic grade of UTUC is essential to the risk-stratification for treatment selection. Predictions of the histopathologic grade based on the visual appearance of papillary UTUC with digital ureteroscopy are often incorrect in comparison with biopsy results and yield low inter-rater agreement. Urologists must be aware of these limitations in the assessment of the tumor grade during digital ureteroscopy to warrant good clinical practice.

Clinical and Patient-reported Outcome Measures in Men Referred for Consideration of Surgery to Treat Lower Urinary Tract Symptoms: Baseline Results and Diagnostic Findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

BACKGROUND: Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). OBJECTIVE: To report participants' sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. DESIGN, SETTING, AND PARTICIPANTS: A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. INTERVENTION: Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick's test, and questionnaire items were compared using Pearson's correlation coefficient. RESULTS AND LIMITATIONS: Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. CONCLUSIONS: Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. PATIENT SUMMARY: We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma.

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.