Prognostic Value of P63 Expression in Muscle-Invasive Bladder Cancer and Association with Molecular Subtypes-Preliminary Report.

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Unveiling the challenges of UTUC biopsies and cytology: insights from a global real-world practice study.

PURPOSE: Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology. METHODS: To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC. RESULTS: We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade. CONCLUSION: Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).

Incidence of complications and urinary incontinence following endoscopic enucleation of the prostate in men with a prostate volume of 80 ml and above: results from a multicenter, real-world experience of 2512 patients.

PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

PURPOSE: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. METHODS: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. RESULTS: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. CONCLUSION: Combined treatment improved RFS and PFS only in patients with Ta disease.

HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role.

Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.

Clinicopathological Features and Survival Analysis in Molecular Subtypes of Muscle-Invasive Bladder Cancer.

Molecular subtyping of bladder cancer (BC) aims to capture the biological heterogeneity of this complex disease in order to provide better patient risk stratification. Immunohistochemical (IHC) markers are regarded as promising surrogates to classify BCs into luminal and basal subtypes in routine practice. We investigated the correlation between the molecular subclassification, assessed through IHC, and the conventional prognostic variables of a cohort of 93 muscle-invasive BCs (MIBCs), with a focus on the pattern of muscularis propria (MP) invasion, and evaluated their association with outcome. Basal, luminal, double-positive (DP), and double-negative (DN) phenotypes were identified according to the coordinate expression of 1 basal (CK5/6) and 2 luminal (CK20, GATA3) markers, and accounted for 33.3%, 32.3%, 3.2%, and 31.2% (Scheme #1) and 9.7%, 60.2%, 26.9%, and 3.2% (Scheme #2). There was a significant association between the pattern of MP invasion and the molecular subtypes according to Scheme #2, in that all 8 basal and DN cases, as well as 83% of DP cases, had a non-infiltrative invasion pattern. No consistent differences were observed in terms of OS and CSS between the molecular subtypes obtained through surrogate IHC markers. In keeping with previous studies, we report the correlation between the identification of BC subtypes and the presence of morphological prognostic factors, supporting the need for a comprehensive pathological evaluation, including clinicopathological and molecular parameters, in order to improve the diagnosis and management of MIBC.

Foggia Prostate Cancer Risk Calculator 2.0: A Novel Risk Calculator including MRI and Bladder Outlet Obstruction Parameters to Reduce Unnecessary Biopsies.

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.

Prostate cancer biomarkers: a practical review based on different clinical scenarios.

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use.

Are Two Meshes Better than One in Sacrocolpopexy for Pelvic Organ Prolapse? Comparison of Single Anterior versus Anterior and Posterior Vaginal Mesh Procedures.

INTRODUCTION: Sacrocolpopexy (SC) is the main treatment option for the repair of anterior and apical pelvic organ prolapse (POP). Indications and technical aspects are not standardized, and the question remains whether it is necessary to place a mesh on both anterior and posterior vaginal walls, particularly in cases with only minor or no posterior compartment prolapse. The present study aimed to compare the anatomical and functional outcomes of single anterior mesh only versus anterior and posterior mesh procedures in SC. MATERIALS AND METHODS: Our prospectively maintained database on POP was used to identify patients who had undergone either abdominal or mini-invasive SC from January 2006 to October 2019. Patients with symptomatic or unmasked stress urinary incontinence (SUI) were not included in the study and were treated using the pubo-vaginal cystocele sling procedure. Objective outcomes included clinical evaluation of pre-existing or de novo POP by the halfway system and POP-q classifications, as well as the development of de novo SUI. Subjective outcomes were assessed using the Pelvic Floor Impact Questionnaire (PFIQ-7) with questions on bladder, bowel, and vaginal functions. Persistent or de novo constipation and overactive bladder were defined as bowel symptoms and urinary urgency/frequency/urinary incontinence after surgery. RESULTS: Ninety-five women with symptomatic anterior and apical POP underwent SC. Forty-one patients were treated with only anterior vaginal mesh (group A), and 54 with anterior and posterior mesh (group B). There were no differences between the pre- and post-operative characteristics of the 2 groups. In group B, there were 2 blood transfusions, 1 wound dehiscence, and 3 mesh erosions/extrusion after abdominal SC (Clavien-Dindo II), and in group A, there was 1 ileal lesion after laparoscopic SC (Clavien-Dindo III). There were no differences between the 2 groups in either anatomical or functional outcomes during 3 years of follow-up. CONCLUSIONS: SC with single anterior vaginal mesh has similar results to SC with combined anterior/posterior mesh, regardless of the surgical approach. The single anterior mesh may reduce the risk of complications (mesh erosion/extrusion), and offers better subjective outcomes with improved quality of life. Anterior/posterior mesh may be justified in the presence of clinically significant posterior POP.

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression.

Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A "consensus" classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation.

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a "consensus" classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.

Pathological diagnosis of Coronavirus-related nephropathy: insight from postmortem studies.

A novel coronavirus pneumonia first occurred in Wuhan, China in early December 2019; the causative agent was identified and named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO), and the resulting disease termed coronavirus disease 2019 (COVID-19), according to the WHO coronavirus disease situation reports. This condition has spread rapidly all over the world and caused more than 125 million cases globally, with more than 2 million related deaths. Two previous outbreaks due to zoonotic coronaviruses have occurred in the last 20 years, namely the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), causing high morbidity and mortality in human populations upon crossing the species barriers. SARS-CoV-2, SARS-CoV, and MERS-CoV show several similarities in pathogenicity and clinical presentations, the latter ranging from asymptomatic infection to severe acute respiratory distress syndrome (ARDS) and multiorgan impairment. Acute kidney injury (AKI) has been commonly reported in patients with CoV infections; therefore, pathological analysis of renal parenchyma in these patients has been carried out in order to improve knowledge about underlying mechanisms. Viral infection has been demonstrated in the renal tubular epithelial cells by electron microscopy (EM), immunohistochemistry (IHC), and in situ hybridization (ISH), although with conflicting results. Light microscopy (LM) changes have been described in the renal parenchyma primarily in the form of acute renal tubular damage, possibly due to direct viral cytopathic effect and immune-mediated mechanisms such as cytokine storm syndrome. In this review, we describe and discuss the spectrum of histological, ultrastructural, and molecular findings in SARS-CoV, MERS-CoV, and SARS-CoV-2-related renal pathology obtained from postmortem studies, as well as intrinsic limitations and pitfalls of current diagnostic techniques.

Improvement of urinary tract symptoms and quality of life in benign prostate hyperplasia patients associated with consumption of a newly developed whole tomato-based food supplement: a phase II prospective, randomized double-blinded, placebo-controlled study.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. The diagnosis of BPH is usually driven by lower urinary tract symptoms (LUTS) that can significantly affect patients' quality of life. This phase II prospective, randomized double-blinded, placebo-controlled study aimed to determine the efficacy and safety of a novel whole tomato-based food supplement on LUTS of patients diagnosed with BPH. METHODS: Forty consecutive patients with histologically proved BPH were randomized 1:1 to receive daily for 2 months a sachet (5 g) of a newly developed whole tomato food supplement (WTFS) (treatment = Group A) or placebo (Group B). Patients were asked to fill the International Prostatic Symptom Score (IPSS) questionnaire before and after treatment. RESULTS: All but 1 patient in Group B successfully completed the scheduled regimen. No side effects were recorded. Unlike placebo, treatment significantly reduced (P < 0.0002) LUTS since mean IPSS decreased from 9.05 ± 1.15 to 7.15 ± 1.04 (paired t-test, two-tailed P-value < 0.001), and improved life quality (P < 0.0001). A trend toward a reduction of total PSA levels was observed in WTFS treated patients (8.98 ng/mL ± 1.52 vs 6.95 ± 0.76, P = 0.065), with changes being statistically significant only in the subgroup of patients with baseline levels above 10 ng/mL (18.5 ng/mL ± 2.7 vs 10.3 ± 2.1, P = 0.009). CONCLUSIONS: The new WTFS may represent a valid option for the treatment of symptomatic BPH patients. Unlike pharmacological treatments, the supplement is side effects free and highly accepted among patients.

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications.

BACKGROUND: The most common bladder cancer (BC) histotype is pure urothelial carcinoma (UC), which may undergo divergent differentiation in some cases. Variant histology (VH) presents along variable morphologies, either single or combined between them or with pure UC. From a clinical standpoint, the vast majority of BC is diagnosed at non-invasive or minimally invasive stages, namely as non-muscle invasive BC (NMIBC). There is a wide range of therapeutic options for patients with NMIBC, according to their clinical and pathological features. However, current risk stratification models do not show optimal effectiveness. Evidence from the literature suggests that VH has peculiar biological features, and may be associated with poorer survival outcomes compared to pure UC. SUMMARY: In order to describe the biological features and prognostic/predictive role of VH in NMIBC, and to discuss current treatment options, we performed a systematic literature search through multiple databases (PubMed/Medline, Google Scholar) for relevant articles according to the following terms, single and/or in combination: "non-muscle invasive bladder cancer," "variant histology," "micropapillary variant," "glandular differentiation," "squamous differentiation," "nested variant," "plasmacytoid variant," and "sarcomatoid variant." We extracted 99 studies including original articles, reviews, and systematic reviews, and subsequently analyzed data from 16 studies reporting on the outcome of NMIBC with VH. We found that the relative rarity of these forms as well as the heterogeneity in study populations and therapeutic protocols results in conflicting findings overall. Key Messages: The presence of VH should be taken into account when counseling a patient with NMIBC, since it may upgrade the disease to high-risk tumor and thus warrant a more aggressive treatment.

Assessing treatment response after intravesical bacillus Calmette-Guerin induction cycle: are routine bladder biopsies necessary?

PURPOSE: To determine the need for routine bladder biopsies (BBs) in assessing response to the induction cycle of intravesical bacillus Calmette-Guérin (BCG) for high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: Our prospectively maintained NMIBC database was queried to identify patients with high-risk disease (carcinoma in situ, high-grade Ta/T1) who underwent BBs after BCG induction cycle. Urine cytology, cystoscopy, and BBs findings were evaluated. RESULTS: A total of 219 patients met the inclusion criteria. Urine cytology was positive in 20 patients and negative in 199; cystoscopy was positive in 35 patients, suspicious in 32 and normal in 152 patients. BBs yielded bladder cancer (BCa) in 43 (19.6%) patients, with a BCa rate of 9.3% in patients with negative cytology and cystoscopy as opposed to 38.0% in patients whereby one or both exams were suspicious/positive. The diagnostic accuracy of urine cytology, cystoscopy, and combined tests was 0.56, 0.70, and 0.71, respectively. The negative predictive value of combined tests was 90.7%. Performing BBs only in patients with positive cytology and/or positive/suspicious cystoscopy would have spared 140 (64%) patients to undergo this procedure while missing BCa in 13 (9.3%) of them, representing 30% of all BCa cases. CONCLUSION: Performing BBs only in patients with positive cytology and suspicious/positive cystoscopy would spare 64% of un-necessary BBs but miss a non-negligible number of BCas. While no data are available regarding the potential consequences of missing such BCas, such information should be taken into account in patient's counselling.

Advanced ureteroscopic techniques for the management of kidney stones.

PURPOSE OF REVIEW: Recent years witnessed significant changes in the endourological management of renal tones because of the development of new, more advanced instruments. Retrograde intrarenal surgery (RIRS) has gained particular advantage from such technological progress and now tends to be considered the gold standard treatment for uncomplicated less than 20 mm renal stones. Using a step-by-step approach, this review aims to highlight current achievements but also unsolved problems in RIRS. RECENT FINDINGS: Several technical details of RIRS, including preoperative stenting, use of ureteral access sheets, lithotripsy method, and renal drainage, remain open to discussion and linked to surgeon's preference. Moreover, there is a wide range of variation in efficacy and safety data, with major complications being episodic but often under-reported. SUMMARY: RIRS has gained increased popularity among the urological community. This is certainly because of the continuous technological advancements, which have continuously improved the RIRS performance but also to the perception of ease and safety of this procedure when compared with the other available treatment modalities, particularly percutaneous nephrolitotomy. Indeed, the reported advances in RIRS technique have significantly improved the outcomes of this procedure but care should be taken not to underestimate its potential challenges.

Contemporary patterns of presentation, diagnostics and management of upper tract urothelial cancer in 101 centres: the Clinical Research Office of the Endourological Society Global upper tract urothelial carcinoma registry.

PURPOSE OF REVIEW: To assess patterns of presentation, diagnostics and treatment in patients with upper tract urothelial carcinoma (UTUC), a multicentre registry was launched. Clinical data of UTUC patients were prospectively collected over a 5-year period. RECENT FINDINGS: Data from 2380 patients were included from 2014 to 2019 (101 centres in 29 countries). Patients were predominantly male (70.5%) and 53.3% were past or present smokers. The majority of patients (58.1%) were evaluated because of symptoms, mainly macroscopic hematuria. Computed tomography (CT) was the most common performed imaging modality (90.5%). A ureteroscopy (URS) was part of the diagnostic process in 1184 (49.7%) patients and 488 (20.5%) patients were treated endoscopically. In total, 1430 patients (60.1%) were treated by a radical nephroureterectomy, 59% without a prior diagnostic URS. Eighty-two patients (3.4%) underwent a segmental resection, 19 patients (0.8%) were treated by a percutaneous tumour resection. SUMMARY: Our data is in line with the known epidemiologic characteristics of UTUC. CT imaging is the preferred imaging modality as also recommended by guidelines. Diagnostic URS gained a stronger position, however, in almost half of patients a definitive treatment decision was made without complete endoscopic information. Only one-third of patients with UTUC are currently treated with kidney sparing surgery.

Nomogram predicting 30-day mortality after nephrectomy in the contemporary era: Results from the SEER database.

OBJECTIVES: To assess contemporary 30-day mortality rates after partial and radical nephrectomy in USA, and to develop a predictive model of 30-day mortality. METHODS: We relied on the National Cancer Institute Surveillance, Epidemiology and End Results database. A multivariable logistic regression analysis was fitted to predict 30-day mortality. A nomogram was built based on the coefficients of the logit function. Internal validation was carried out using the leave-one-out cross-validation. Calibration was graphically investigated. RESULTS: A total of 102 146 patients who underwent partial nephrectomy (n = 36 425; 35.7%) or radical nephrectomy (n = 65 721; 64.3%) between 2005 and 2015 were included in the analysis. The median age at diagnosis was 62 years. A total of 11 921 (11.7%) patients were African American. The clinical stage was T1-T2 in 79 452 (77.8%), T3 in 16 141 (15.8%) and T4/T1-4-M1 in 6553 (6.4%) patients. Overall, 497 deaths occurred during the initial 30 days after nephrectomy (0.49% 30-day mortality rate). Stratified by type of surgery, the 30-day mortality rate was 0.16% for partial nephrectomy and 0.67% for radical nephrectomy. At univariate analyses, age, tumor size, stage and surgical procedure emerged as predictors of 30-day mortality (all P < 0.001). All of these covariates were included in the multivariable logistic regression model. The area under the curve after leave-one-out cross-validation was 0.808 (95% confidence interval 0.788-0.828), and the model showed good calibration in the range of predicted probability <10%. CONCLUSIONS: Contemporary rates of 30-day mortality in patients undergoing radical or partial nephrectomy are very low. Age and tumor stage are key determinants of 30-day mortality. We present a predictive model that provides individual probabilities of 30-day mortality after nephrectomy, and it can be used for patient counseling prior surgery.

Using biomarkers in patients with positive multiparametric magnetic resonance imaging: 4Kscore predicts the presence of cancer outside the index lesion.

OBJECTIVES: To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy. METHODS: We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation. RESULTS: The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability <12.5% resulted in 39.5% (n = 101) fewer standard biopsies and a 33.9% (n = 20) reduction of detecting grade group 1 disease, while missing grade group ≥2 in 5.2% (n = 4) using standard biopsy only and 1.1% (n = 1) using standard biopsy + targeted biopsy. CONCLUSIONS: 4Kscore in combination with multiparametric magnetic resonance imaging can help to reduce unnecessary standard biopsy and decrease detection of clinically insignificant prostate cancer.