Fibroblast Activation Protein-α and the Immune Landscape: Unraveling T1 Non-muscle-invasive Bladder Cancer Progression.

Background and objective: The tumor microenvironment (TME) in non-muscle-invasive bladder cancer (NMIBC) plays an important role in the anticancer response. We aimed to identify the prognostic biomarkers in the TME of patients with NMIBC for progression to ≥T2. Methods: From our institutional database, 40 patients with T1 high-risk NMIBC who progressed were pair matched for Club Urologico Español de Tratamiento Oncologico (CUETO) progression variables with 80 patients who never progressed despite longer follow-up. Progression was defined as ≥T2 or extravesical disease. Patients were treated at least with bacillus Calmette-Guérin (BCG) induction (five or more of six doses). Immunohistochemical (IHC) markers for the TME were used on tissue at first T1 diagnosis: CD8-PanCK, GZMB-CD8-FOXP3, CD163, PD-L1 SP142/SP263, fibroblast activation protein-α (FAP), and CK5-GATA3. Full tissue slides were annotated digitally. Relative marker area (IHC-positive area/total area) or density (IHC-positive cells per area; n/mm2) was calculated, differentiating between regions of interest (ROIs; T1, Ta, and carcinoma in situ) and between compartments (stromal, epithelial, and combined). Differences in IHC variables were assessed using the t test, for continuous variables using analysis of variance and comparisons of more than two groups using Tukey's test. Conditional logistic regression for progression at 5-yr follow-up was performed with clusters based on pair matching. Key findings and limitations: Only FAP expression (increase per 50%) in T1 (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.04-1.70) and all ROIs combined (OR: 1.62; 95% CI: 1.14-2.29) correlated significantly with progression. None of the other clinicopathological/IHC variables correlated with progression. Conclusions and clinical implications: FAP is a potential prognostic biomarker for progression in high-risk NMIBC. FAP is a marker for cancer-associated fibroblasts and is linked to immunosuppression and neoangiogenesis, which makes future investigation clinically relevant. Patient summary: We found that progression of high-risk non-muscle-invasive bladder cancer to muscle-invasive disease is less in patients with lower fibroblast activation protein-α (FAP) expression, which is a marker for cancer-associated fibroblasts.

A software package for efficient patient trajectory analysis applied to analyzing bladder cancer development.

We present the Patient Trajectory Analysis Library (PTRA), a software package for explorative analysis of patient development. PTRA provides the tools for extracting statistically relevant trajectories from the medical event histories of a patient population. These trajectories can additionally be clustered for visual inspection and identifying key events in patient progression. The algorithms of PTRA are based on a statistical method developed previously by Jensen et al, but we contribute several modifications and extensions to enable the implementation of a practical tool. This includes a new clustering strategy, filter mechanisms for controlling analysis to specific cohorts and for controlling trajectory output, a parallel implementation that executes on a single server rather than a high-performance computing (HPC) cluster, etc. PTRA is furthermore open source and the code is organized as a framework so researchers can reuse it to analyze new data sets. We illustrate our tool by discussing trajectories extracted from the TriNetX Dataworks database for analyzing bladder cancer development. We show this experiment uncovers medically sound trajectories for bladder cancer.

Prognosis of patients with T1 low-grade urothelial bladder cancer treated with bacillus Calmette-Guérin immunotherapy.

BACKGROUND: The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of bacillus Calmette-Guérin (BCG) treated T1LG tumors and if it differs from other NMIBC (non-muscle-invasive bladder cancer) representatives. The aim of this study was to analyse recurrence-free survival (RFS) and progression-free survival (PFS) in patients with T1LG bladder cancers treated with BCG immunotherapy. METHODS: A multi-institutional and retrospective study of 2510 patients with Ta/T1 NMIBC with or without carcinoma in situ (CIS) treated with BCG (205 T1LG patients) was performed. Kaplan-Meier estimates and log-rank test for RFS and PFS to compare the survival between TaLG, TaHG, T1LG, and T1HG NMIBC were used. Also, T1LG tumors were categorized into EAU2021 risk groups and PFS analysis was performed, and Cox multivariate model for both RFS and PFS were constructed. RESULTS: The median follow-up was 52 months. For the T1LG cohort, the estimated RFS and PFS rates at 5-year were 59.3% and 89.2%, respectively. While there were no differences in RFS between NMIBC subpopulations, a slightly better PFS was found in T1LG NMIBC compared to T1HG (5-year PFS; T1LG vs. T1HG: 82% vs. 89%; P<0.001). A heterogeneous classification of patients with T1LG NMIBC was observed when EAU 2021 prognostic model was applied, finding a statistically significant worse PFS in patients classified as high-risk T1LG (5-year PFS; 81.8%) compared to those in intermediate (5-year PFS; 93,4%), and low-risk T1LG tumors (5-year PFS; 98,1%). CONCLUSIONS: The RFS of T1LG was comparable to other NMIBC subpopulations. The PFS of T1LG tumors was significantly better than of T1HG NMIBC. The EAU2021 scoring model heterogeneously categorized the risk of progression in T1LG tumors and the high-risk T1LG had the worst PFS.

Prognostic role of the endothelial cell-specific molecule-1 histopathologic expression in renal cell cancer.

INTRODUCTION: To measure the level of endothelial cell-specific molecule-1 (ESM-1) expression among the Renal Cell Cancer (RCC) variants using by immunohistochemical method and determine the relationship between ESM-1 expression and RCC prognosis. MATERIALS AND METHODS: ESM-1 immunoreactivity scores (IR) were measured in appropriate renal tumoral tissue blocks of 153 consecutive RCC patients in this retrospective analysis of prospectively collected data. Mean ESM-1 IR scores were calculated in patients who were pathologically diagnosed with clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). Progression-free survival and overall survival were evaluated using the log-rank test according to ESM-1 IR scores. Survival rates were calculated using Kaplan-Meier survival analysis. RESULTS: In the ccRCC group, the mean ESM-1 IR scores of those with local invasion were significantly higher than those without local invasion (P = 0.014). The mean ESM-1 IR score of patients with metastatic ccRCC was significantly higher than those with non-metastatic ccRCC (P < 0.001). Considering all patients regardless of RCC subtype pathologies, the mean ESM-1 IR score in clinical stage 1 tumor was 3.82 ± 1.98, 4.87 ± 1.74 in clinical stage 2, 5.88 ± 2 in clinical stage 3, and 6.60 ± 2.23 in clinical stage 4. The mean ESM-1 IR score of patients with metastatic ccRCC was significantly higher than those with non-metastatic ccRCC (P < 0.001). The mean follow-up period for all patients in this study was 71 months (range 1-120 months). It has been shown that the higher the ESM-1 IR score, the lower the 10-year overall survival and disease-free survival rates (P = 0.026, P = 0.005). CONCLUSION: Immunohistochemical expression of ESM-1 may be a promising prognostic biomarker in RCC. Currently, some prognostic scoring systems are available for patients with localized and metastasized RCC. Incorporating ESM-1 expression in RCC into these existing prognostic scoring systems could improve these models and enhance the quality of individual oncologic management in RCC patients.

Quality Control Indicators for Transurethral Resection of Bladder Tumor: Results from an Embedded Belgian Multicenter Prospective Registry.

BACKGROUND: Quality control indicators (QCIs) can be used to objectively evaluate guideline adherence and benchmark quality among urologists and centers. OBJECTIVE: To assess six QCIs for non-muscle-invasive bladder cancer (NMIBC) using a prospective registry of transurethral resection of bladder tumor (TURBT) procedures. DESIGN, SETTING, AND PARTICIPANTS: Clinical data for TURBT cases were prospectively collected using electronic case report forms (eCRFs) embedded in the electronic medical record in three centers during 2013-2017. Pathological data were collected retrospectively. Patients with T0 disease or prior T2 disease were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed six QCIs: complete resection (CR) status, presence of detrusor muscle (DM), re-TURBT, single instillation of mitomycin C (MMC), start of bacillus Calmette-Guérin (BCG) therapy, and therapy ≤6 wk after diagnosis. We assessed the quality of reporting on QCIs and compliance with QCIs, compared compliance between centers and over time, and investigated correlation between compliance and recurrence-free survival (RFS). RESULTS AND LIMITATIONS: Data for 1350 TURBT procedures were collected, of which 1151 were included for 907 unique patients. The distribution of European Association of Urology risk categories after TURBT was 271 with low risk, 464 with intermediate risk, and 416 with high risk. The quality of reporting for two QCIs was suboptimal, at 35% for DM and 51% for BCG. QCI compliance was 97% for CR, 31% for DM, 65% for MMC, 33% for re-TURBT, 39% for BCG, and 88% for therapy ≤6 wk after diagnosis. Compliance with all QCIs differed significantly among centers. Compliance with MMC and re-TURBT increased significantly over time, which could be attributed to one center. Compliance with MMC was significantly correlated with RFS. The main study limitation is the retrospective collection of pathology data. CONCLUSIONS: A TURBT registry consisting of eCRFs to collect pathology and outcome data allowed assessment of QCIs for NMIBC. Our study illustrates the feasibility of this approach in a real-life setting. Differences in performance on QCIs among centers can motivate urologists to improve their day-to-day care for patients with NMIBC, and can thus improve clinical outcomes. PATIENT SUMMARY: Our study demonstrates that quality control indicators for treatment of bladder cancer not invading the bladder muscle can be evaluated using electronic medical records. We assessed results for 1151 procedures in 907 individual patients to remove bladder tumors between 2013 and 2017 at three centers in Belgium. Compliance with the quality control indicators differed between centers, increased over time, and was correlated with recurrence of disease.

Augmenting THerapeutic Effectiveness Through Novel Analytics (ATHENA) - A Public and Private Partnership Project Funded by the Flemish Government (VLAIO).

The complexity and heterogeneity of cancers leads to variable responses of patients to treatments and interventions. Developing models that accurately predict patient's care pathways using prognostic and predictive biomarkers is increasingly important in both clinical practice and scientific research. The main objective of the ATHENA project is to: (1) accelerate data driven precision medicine for two use cases - bladder cancer and multiple myeloma, (2) apply distributed and privacy-preserving analytical methods/ algorithms to stratify patients (decision support), (3) help healthcare professionals deliver earlier and better targeted treatments, and (4) explore care pathway automations and improve outcomes for each patient. Challenges associated with data sharing and integration will be addressed and an appropriate federated data ecosystem will be created, enabling an interoperable foundation for data exchange, analysis and interpretation. By combining multidisciplinary expertise and tackling knowledge gaps in ATHENA, we propose a novel federated privacy preserving platform for oncology research.

Stromal marker fibroblast activation protein drives outcome in T1 non-muscle invasive bladder cancer.

Fibroblast activation protein-α (FAP) is a transmembrane peptidase and a surrogate marker for cancer-associated fibroblasts (CAFs). FAP has been linked to worse prognosis and therapy resistance in several cancers. We hypothesised that FAP might have a prognostic 3biomarker potential to stratify patients with high-grade (HG) T1 non-muscle-invasive bladder cancer (NMIBC). We selected 30 patients with HG T1 NMIBC that progressed to ≥T2 disease which were pair-matched based on CUETO progression score variables with 90 patients that did not progress. After revision a final cohort of 86 patients was retained. Slides were stained for FAP, the luminal marker GATA3 and the basal marker CK5. All HG T1 tumour regions of interest (ROIs) within each patient were annotated, analysed and scored using image analysis software. FAP expression in HG T1 ROIs was significantly higher in progressors vs. non-progressors and was prognostic for recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival. FAP expression in HG T1 ROIs remained strongly prognostic for these outcomes in a bivariable model corrected for adequate BCG per FDA definition. Expression of GATA3 and CK5 did not differ between progressors vs. non-progressors, and were not prognostic for these outcomes. FAP might serve as an easily applicable prognostic biomarker to risk-stratify patients with HG T1 NMIBC if these results are prospectively validated in a larger series.

Cytokeratin 5 and cytokeratin 20 inversely correlate with tumour grading in Ta non-muscle-invasive bladder cancer.

Cytokeratin 5 is a marker of basal molecular subtypes of muscle-invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high-grade (HG) disease in Ta non-muscle-invasive bladder cancer (NMIBC). Therefore, to understand the basal-luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low-grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up-regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC.

Comparison of Two Different Bipolar Energy Resources in Transurethral Resection of Bladder Tumors.

PURPOSE: To determine whether the use of different bipolar resources is associated with different results on tissue and perioperative parameters in patients undergoing bipolar transurethral bladder tumor resection (bTURBT). METHODS: In this single-center prospective study, patients diagnosed with bladder tumor randomized to undergo TURBT either with a Gyrus PlasmaKinetic system (n = 62) or Olympus TUR in saline (TURis) system (n = 51). Primary endpoint was to evaluate the alteration of patients' perioperative parameters, while secondary aim was to assess the thermal effect of these 2 different bipolar devices on the resected tissue samples by a grading system determined by tissue characteristics. RESULTS: One hundred thirteen patients were randomized in the study, and 43 were excluded from the analysis due to the exclusion criteria. There were no significant differences between the groups in terms of mean age, tumor site, number of tumors, operative time, alteration in hemoglobin or hematocrit, blood transfusion rate, catheterization time, and postoperative stay. On the other hand, the ratio of obturator jerk was significantly higher in the Olympus TURis group (p = 0.028). The histopathological analyses of both groups determined muscularis propria and cautery artifact presence without a statistically significant difference (χ2: 0.476, p = 0.788). CONCLUSION: Although the perioperative complications of bTURBT are low in nature, bladder perforation resulted from obturator jerk still poses a risk for extravesical tumor implantation. Urologists should be aware of this risk especially when they are using a TURis system.

A survey analysis of knowledge levels of urologists about radiation safety and fluoroscopy use.

AIMS: To evaluate the awareness of the use of fluoroscopy in endourological procedures, as well as the theoretical and practical applications of preventive measures. MATERIAL AND METHOD: Between May 2018 and April 2019, a 26-question survey prepared using Google Docs was sent to urologists via email. Personal information, radiation training and behaviours related to radiation and fluoroscopy usage, and the use of protective equipment were queried. RESULTS: A total of 226 participants fully completed and returned the email survey. Of the 226 participants, 78 (34.5%) were academics, 44 (19.4%) were residents while 104 (46.1%) were experts. More than 60% of the participants stated that they participated in the operation requiring less than five fluoroscopy use per week. The majority of operations requiring fluoroscopy consisted of endourological procedures. The lead apron was used by 93% of the participants, but the use of protective glasses and gloves was very low (3.5%). The majority of academicians, experts and residents did not use dosimeters (76.9%, 82.7% and 81.8%, respectively). More than 50% of the participants did not have literature information about the harmful effects of radiation with the use of fluoroscopy. The most common complaints on the day of fluoroscopy were fatigue and headache. CONCLUSION: The lack of information regarding the radiation protection measures and harmful effects of radiation is common among urologists in Turkey. Therefore, systematic training programs on fluoroscopy use and radiation exposure should be provided during urology residency.

Comparison of Two Single-Incision Mini-Slings for the Treatment of Incontinence.

INTRODUCTION: This study aimed to compare the safety and efficacy of 2 single-incision mini-sling (SIMS) systems with different designs of anchoring mechanism. METHODS: The records of patients who have been operated for the treatment of female stress urinary incontinence (SUI) with 2 different SIMS systems were retrospectively evaluated. Patient characteristics, physical examination results, and quality of life (QoL) questionnaires were used to evaluate the patients. Primary efficacy endpoints were the cure and failure rates. Secondary efficacy endpoints were complications and differences in QoL questionnaires. RESULTS: Eighty-three patients from group 1 (Ophira SIMS system) and 77 patients from group 2 (Gallini SIMS system) were evaluated. There was no significant difference between the 2 groups regarding patient characteristics. The objective cure rates were found to be 83.1 and 79.2% in group 1 and group 2, respectively (p = 0.09). Mesh-related complications, such as anchor displacement, bladder erosion, vaginal erosion, and groin pain, were more common in group 1. No severe complications were observed. For both groups, a significant improvement in all scores of QoL questionnaires was observed after surgery; however, the differences between 2 groups were not significant. CONCLUSIONS: The present study showed that the treatment of female SUI with 2 different SIMS systems had similar efficacy, complication rates, and scores in QoL questionnaires.

Retrograde intrarenal surgery of renal stones: a critical multi-aspect evaluation of the outcomes by the Turkish Academy of Urology Prospective Study Group (ACUP Study).

AIMS: To outline and evaluate the incidence, management and follow-up of the residual fragments (RFs) following retrograde intrarenal surgery (RIRS) of renal stones by the Turkish Academy of Urology Prospective Study Group (ACUP Study). METHODS: Following the ethical committee approval, 15 centers providing data regarding the incidence, management, and follow-up of RFs after RIRS were included and all relevant information was recorded into the same electronic database program ( https://acup.uroturk.org.tr/ ) created by Turkish Urology Academy for Residual Stone Study. RESULTS: A total of 1112 cases underwent RIRS for renal calculi and RFs were observed in 276 cases (24.8%). Of all the parameters evaluated, our results demonstrated no statistically significant relation between preoperative DJ stenting and the presence of RFs (χ2 (1) = 158.418; p = 0.099). RFs were significantly higher in patients treated with UAS (82 patients, 29.3%) during the procedure compared to the cases who did not receive UAS (194 patients, 23.3%) (χ2 (1) = 3.999; p = 0.046). The mean period for a secondary intervention after RIRS was 28.39 (± 12.52) days. Regarding the procedures applied for RF removal, re-RIRS was the most commonly performed approach (56%). CONCLUSIONS: Despite the reported safe and successful outcomes, the incidence of RFs is higher, after the RIRS procedure particularly in cases with relatively larger calculi. Such cases need to be followed in a close manner and although a second flexible ureteroscopy is the treatment of choice for fragment removal in the majority of these patients, shock wave lithotripsy and percutaneous nephrolithotomy may also be preferred in selected cases.

Comparison of De Ritis Ratio and other systemic inflammatory parameters for the prediction of prognosis of patients with transitional cell bladder cancer.

OBJECTIVE: To investigate the clinical value of preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) (DRR) in patients with transitional cell bladder cancer (TCBC) at initial diagnosis. The secondary objective was to investigate the status of systemic inflammatory parameters, such as neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR) and platelet-monocyte ratio (PMR). MATERIALS AND METHODS: The records of patients with primary TCBC who underwent transurethral resection were retrospectively evaluated. The relationship of DRR and systemic inflammatory parameters with clinicopathological findings, recurrence and progression status was evaluated separately. RESULTS: There was no significant difference in the DRR according to the clinicopathological findings, recurrence and progression. Significant differences were found between the NLR and the patient groups for tumour diameter, tumour stage, tumour grade and progression. In univariate analysis, the LMR was found to be associated with progression, and also the PLR and LMR were found to be associated with recurrence. Decrease in LMR and increase in LMR score demonstrated by multiple analysis was shown as independent predictors of progression and recurrence development. CONCLUSIONS: This paper shows a positive correlation between poor prognosis in TCBC and the systemic inflammatory markers, namely NLR, LMR, PLR and PMR, but not DRR.

Pushing the limits of metastasis-directed treatment in metastatic renal cell carcinoma in the era of targeted therapy.

OBJECTIVE: To assess the role of metastasis directed therapy and in particular surgical metastasectomy (MxT) in metastatic renal cell carcinoma (mRCC) in the era of targeted therapy. METHOD: The files of all patients who underwent MxT for treatment of mRCC in University Hospitals Leuven between 1989 and 2015 were reviewed. RESULTS: One hundred and thirty eight patients met the inclusion criteria. Mean age at MxT was 59.3 (IQR: 57.5-61.0) years. Median follow-up was 50.1 (42.3-63.8) months. Due to adequate patient selection, 91.9% of MxT achieved no evidence of disease status, which resulted in long median overall survival of 87.8 (63.8-113.4) months and median cancer specific survival of 92.8 (69.5-123.4) months. On multivariate analysis, primary tumor stage >pT2 (hazard ratio [HR] 2.79 [1.47-5.28] P= 0.002), unreached no evidence of disease status (HR 8.62 [3.19-23.32] P< 0.001), presence of nonpulmonary metastasis (HR 2.29 [1.02-5.10] P= 0.0449) and sarcomatoid dedifferentiation in the primary tumor (HR 4.52 [1.15-17.69] P= 0.03) significantly impacted overall survival. Survival did not differ for MxT performed before and after the advent of vascular endothelial growth factor receptor-tyrosine kinase inhibitors. DISCUSSION: Our study confirms the validity of MxT in mRCC in the tyrosine kinase inhibitors era. MxT should be considered in mRCC whenever the patient is fit enough to undergo surgery and complete removal of metastasis is considered possible, independent of number, location, and chronology of appearance of metastasis. Patients with pulmonary metastasis only, seem to be the best candidates for surgical MxT.

Metastasectomy of oligometastatic urothelial cancer: a single-center experience.

BACKGROUND: Survival in patients with urothelial cancer (UC) recurrence after initial treatment with curative intent is limited and treatment options are sparse. Metastasectomy could be considered a treatment option in selected cases. Identifying prognostic factors for survival can be used to counsel patients and aid multidisciplinary teams in making treatment decisions. METHODS: We collected a retrospective case series of patients undergoing metastasectomy for oligometastatic UC between 1999 and 2018 at University Hospitals Leuven. Oligometastatic UC was defined as recurrence of UC in a single organ with ≤3 metastases. Survival outcomes of interest were: overall survival (OS), cancer-specific survival (CSS), and secondary recurrence-free survival (RFS2). Complications were reported using the Clavien-Dindo classification (CDC). Survival analysis are descriptive and were performed using Kaplan-Meier plots to visualize survival data and log-rank was used to compare survival between groups. RESULTS: From 1999 to 2018, a total of 22 patients underwent metastasectomy of oligometastatic UC. Metastasectomy sites were: pulmonary (59.1%), loco-regional (13.6%), hepatic (9.1%), adrenal (4.5%), testicular (4.5%), nodal above aortic bifurcation (4.5%), and renal transplant (4.5%). The 5-year OS, CSS and RFS2 after metastasectomy were 51.4%, 57.0%, and 49.9%, respectively. Patients with primary upper tract urothelial cancer (UTUC) involvement and patients treated with hepatic metastasectomy had a significantly worse OS, CSS, and RFS2. Patients with a lesion size >8 mm and patients with >1 pulmonary lesion had a significantly worse CSS. Two CDC grade 3B occurred during follow-up and were both non-procedure related. CONCLUSIONS: Metastasectomy of oligometastatic UC is feasible and can achieve durable cancer control in a highly selected subgroup of patients. Our results suggest that patients with hepatic metastases or primary UTUC involvement could be considered poor candidates for metastasectomy, while patients with a small (<8 mm) or solitary pulmonary lesion might benefit most. These findings should be validated in multi-institutional collaborations or prospective clinical studies.

The Increased Risk of Complicated Ureteral Stones in the Era of COVID-19 Pandemic.

Background: Ureteral stone disease may be an emergent condition if the appropriate management is not performed in a timely manner. As the coronavirus disease 2019 (COVID-19) continues to spread globally, isolation and restriction orders taken by the governments have become the cores to control the pandemic. In this study, we, therefore, aimed to investigate the ureteral stone presentations in a high-volume university hospital during the COVID-19 restriction order period. Materials and Methods: The data of 149 patients who were hospitalized due to ureteral stone both during the COVID-19 pandemic restriction period and the corresponding period (non-COVID-19) of the previous year were collected and analyzed retrospectively. Unpaired Student's t-test was used to compare continuous variables. The categorical data were assessed using Chi-square and Fisher's exact tests. Results: Of 149 patients, 35 were hospitalized in the COVID-19 restrictions period. While the mean age and the stone characteristics of the two groups did not differ significantly, serum creatinine levels (1.9 ± 1.85 vs 1.15 ± 0.64) and the white blood cell counts (12.45 ± 6.54 vs 8.21 ± 4.15) at hospital admission were significantly higher in the COVID-19 restrictions group (p = 0.034 and p = 0.005, respectively). According to the priority classification recommendations of the European Urology Guidelines Office Rapid Reaction Group for urolithiasis applicable during the COVID-19 pandemic, a significant difference was observed between the two periods (X2 = 9.907, p = 0.019). In particular, the rate of emergency cases was found more than threefold in the COVID-19 period. Although there was no significant difference in terms of the grade of hydronephrosis at hospital admission between the two groups, the rates of grade 3 and 4 hydronephrosis were higher in the COVID-period group (1.8- and 3.3-fold, respectively). Conclusion: The rate of complicated ureteral stone disease significantly increased during the COVID-19 restrictions period. Urologists should prioritize the patients most in need of urgent care during COVID-19-like biosocial crisis.

The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival after radical cystectomy: external validation in a large bi-institutional cohort.

OBJECTIVE: To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients. PATIENTS AND METHODS: Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model. RESULTS: A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models. CONCLUSION: We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.

Prognostic score predicts overall survival following complete urinary tract extirpation.

Purpose: To evaluate the oncological outcome and complications of patients treated with complete urinary tract extirpation (CUTE) in our department, and to identify prognostic factors for survival.Methods: Clinico-pathological data of patients treated with one-step or stepwise CUTE between 1999 and 2017 were collected retrospectively. Complications were classified according to the modified Clavien-Dindo classification (CDC) in the early (≤30 days) and late (>30 days) follow-up. Log-rank test was used to assess independent predictors of overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS).Results: Twenty-five patients (20 male) underwent CUTE (16 one-step) for BC + unilateral/bilateral UTUC. Minor (CDC 1-2) and major (CDC3-5) complications were observed in 72% and 40% of patients, respectively, in the early postoperative period (≤30 days). Five (20%) patients died in the perioperative period (CDC 5) with a median OS of 52 days (range: 25-77). Median time to last follow-up or death was 30 months (range: 0-161). Median OS was 50 months (95% Confidence Interval [CI]: 22-118 months), while median CCS and RFS were not reached. The 5-year OS, CSS and RFS were 42.7%, 69.6% and 66.7%, respectively. A score for determining which patients would benefit from CUTE was arbitrarily developed, and showed that the patients with a score of 0-2 points (good prognosis) had a better OS than the patients with a poor prognosis (3-4 points) in the log-rank test.Conclusions: Because of lower OS rates, patients with ESRD or with a CUTE score of 3-4 points are probably not ideal candidates for CUTE.