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.

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.

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 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.

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.

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.

Pelvic organ prolapse repair with a trocarless mesh system: two-year results.

INTRODUCTION AND HYPOTHESIS: Our aim was to investigate the efficacy of the EndoFast Reliant™ system, which is a novel trocarless mesh technology for the treatment of pelvic organ prolapse (POP). METHODS: This was a retrospective cohort study including 31 female patients with POP who underwent vaginal repair. Total follow-up duration was 24 months. All patients were evaluated with a clinical history, POP-Q measures, pelvic ultrasound, body mass index (BMI), questionnaires on symptoms, and quality of life scoring system. RESULTS: The mean age was 53 ± 9.7 years, and the mean BMI was 28.5 ± 3.9 kg/m2. The BMI of 20 patients was < 30 kg/m2. No intraoperative complications occurred. Prolapse was anatomically resolved in 87.1% of patients at 2-year follow-up. Four patients presented stage 1 non-symptomatic prolapse recurrence. De novo stress urinary incontinence developed in four (12.9%) cases and de novo urgency developed in two (6.4%) cases; all were diagnosed and treated easily with oral medication. One case of mesh exposure was found and treated conservatively. There was no migration of fasteners or mesh. Urinary retention, postoperative groin pain, and dyspareunia were not observed. CONCLUSIONS: The EndoFast Reliant™ system was found successful with high success rates, short learning time and very low complication rates in our study. However, further prospective studies with higher patient numbers and longer follow-up durations are needed to reach definitive conclusions.

Genito-urinary genomics and emerging biomarkers for immunomodulatory cancer treatment.

Immunotherapy is gradually becoming a key factor in the therapeutic algorithm for patients with genito-urinary (GU) cancers at different stages of disease. Robust and reliable biomarkers are crucial for an appropriate inclusion of patients in clinical trials and for a reliable patient selection for treatments with immunomodulatory drugs. The increasing knowledge on the genomic landscape of GU cancers supports stratification of patients for targeted therapies. This review focusses on emerging biomarkers and the role of genomics in predicting clinical benefit to immunomodulatory agents in GU cancers. Based on cancer incidences and available data we restricted this overview to bladder, prostate and renal cancer.

Impact of neoadjuvant chemotherapy on short-term complications and survival following radical cystectomy.

OBJECTIVES: To compare perioperative and short-term postoperative complication rates between patients receiving radical cystectomy (RC) after neoadjuvant chemotherapy (NAC) and patients undergoing RC alone. Secondary objectives were to compare overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS: Clinico-pathological data of all patients who received RC between 1996 and 2015 were retrospectively collected. Only patients with RC for muscle-invasive bladder cancer were included in the final analysis. Short-term (30-day) postoperative complications were assessed by registering the Clavien-Dindo classification (CDC) and dividing into sub-groups: low-grade (LGC) CDC 1-2 and high-grade (HGC) CDC 3-5. To compare populations with similar age, comorbidities and preoperative creatinine, we used a propensity score-adjusted statistical model. Pre- and perioperative predictors of short-term complications were identified using uni- and multivariable models. Survival was assessed using Kaplan-Meier analysis. RESULTS: A total of 491 patients undergoing RC were included, of whom 102 (20.8%) received NAC. After propensity score covariate adjustment, there was no significant difference in postoperative complications between patients undergoing NAC plus RC and RC alone with an overall complication rate of 69% and 66%, respectively. No significant differences in the 30-day HGC rates (11.76% and 11.83%, respectively) were observed. NAC plus RC patients had worse prognostic factors at baseline; nevertheless, after correction for group differences OS and CSS did not differ from RC only group (5-year OS 61.3% vs. 50.2%, and 5-year CSS 61.8% vs. 57.9% respectively, p > 0.05 for all). CONCLUSION: In appropriately selected patients, exposure to NAC is not associated with increased short-term complications.

The effect of bladder sensation on uroflowmetry parameters in healthy young men.

AIMS: To investigate the effect of the bladder sensation grade on uroflowmetry parameters. METHODS: Fifty healthy volunteering young men were enrolled in the present study. In total, three uroflowmetry evaluations were made. Qmax , Qave , VV, and PVR urine was obtained three times in three described bladder sensation grades, nearly at the same time of the day. RESULTS: The mean age of the participants in the present study is 29.08 ± 3.8 years. The mean Qmax values of the volunteers were 17.4 ± 4.8 ml/s, 24.1 ± 6.0 ml/s, and 29.6 ± 6.5 ml/s in the first, second, and third, voiding desire grades, respectively. The mean Qave values were 9.9 ± 2.1 ml/s, 12.9 ± 2.9 ml/s, and 15.9 ± 4.0 ml/s for each of the voiding desire grades mentioned. A statistically significant difference was obvious for all three bladder sensation grades in terms of Qmax and Qave values (P = 0.000). However, no statistically significant difference was seen regarding the PVR urine volumes. The mean voided volume in the first, second and third uroflowmetry were 140 ± 42 ml, 245 ± 64 ml, and 449 ± 105 ml, respectively. The highest Qmax and Qave values were obtained when the desire to void was urgent. CONCLUSIONS: The findings of the study show that, uroflowmetry evaluations are to be made if the patients have a strong desire to void. Only thus the highest Qmax values can be obtained; yet, the degree of perceived bladder sensation does not have a statistically significant impact on PVR quantity. Neurourol. Urodynam. 35:622-624, 2016. © 2015 Wiley Periodicals, Inc.

A novel cannulation technique for difficult urethral catheterization.

INTRODUCTION: To propose a novel cannulation technique for difficult urethral catheterization procedures. TECHNIQUE: The sheath tip of an intravenous catheter is cut off, replaced to the needle tip and pushed through the distal drainage side hole to Foley catheter tip, and finally withdrawn for cannulation. In situations making urethral catheterization difficult, a guide wire is placed under direct vision. The modified Foley catheter is slid successfully over the guide wire from its distal end throughout the urethral passage into the bladder. RESULTS: The modified Foley catheter was used successfully in our clinic in cases requiring difficult urethral catheterization. CONCLUSIONS: This easy and rapid modification of a Foley catheter may minimize the potential complications of blind catheter placement in standard catheterization.

Transperitoneal versus extraperitoneal robot-assisted laparoscopic radical prostatectomy: A prospective single surgeon randomized comparative study.

OBJECTIVES: To compare operative, pathological, and functional results of transperitoneal and extraperitoneal robot-assisted laparoscopic radical prostatectomy carried out by a single surgeon. METHODS: After having experience with 32 transperitoneal laparoscopic radical prostatectomies, 317 extraperitoneal laparoscopic radical prostatectomies, 30 transperitoneal robot-assisted laparoscopic radical prostatectomies and 10 extraperitoneal robot-assisted laparoscopic radical prostatectomies, 120 patients with prostate cancer were enrolled in this prospective randomized study and underwent either transperitoneal or extraperitoneal robot-assisted laparoscopic radical prostatectomy. The main outcome parameters between the two study groups were compared. RESULTS: No significant difference was found for age, body mass index, preoperative prostate-specific antigen, clinical and pathological stage, Gleason score on biopsy and prostatectomy specimen, tumor volume, positive surgical margin, and lymph node status. Transperitoneal robot-assisted laparoscopic radical prostatectomy had shorter trocar insertion time (16.0 vs 25.9 min for transperitoneal robot-assisted laparoscopic radical prostatectomy and extraperitoneal robot-assisted laparoscopic radical prostatectomy, P < 0.001), whereas extraperitoneal robot-assisted laparoscopic radical prostatectomy had shorter console time (101.5 vs 118.3 min, respectively, P < 0.001). Total operation time and total anesthesia time were found to be shorter in extraperitoneal robot-assisted laparoscopic radical prostatectomy, without statistical significance (200.9 vs 193.2 min; 221.8 vs 213.3 min, respectively). Estimated blood loss was found to be lower for extraperitoneal robot-assisted laparoscopic radical prostatectomy (P = 0.001). Catheterization and hospitalization times were observed to be shorter in extraperitoneal robot-assisted laparoscopic radical prostatectomy (7.3 vs 5.8 days and 3.1 vs 2.3 days for transperitoneal robot-assisted laparoscopic radical prostatectomy and extraperitoneal robot-assisted laparoscopic radical prostatectomy, respectively, P < 0.05). The time to oral diet was significantly shorter in extraperitoneal robot-assisted laparoscopic radical prostatectomy (32.3 vs 20.1 h, P = 0.031). Functional outcomes (continence and erection) and complication rates were similar in both groups. CONCLUSIONS: Extraperitoneal robot-assisted laparoscopic radical prostatectomy seems to be a good alternative to transperitoneal robot-assisted laparoscopic radical prostatectomy with similar operative, pathological and functional results. As the surgical field remains away from the bowel, postoperative return to normal diet and early discharge can be favored.

Laparoscopic pudendal nerve decompression and transposition combined with omental flap protection of the nerve (Istanbul technique): technical description and feasibility analysis.

BACKGROUND: We aimed in this study to investigate the efficacy of laparoscopic pudendal nerve decompression and transposition (LaPNDT) in the treatment of chronic pelvic pain due to pudendal neuralgia. Pudendal nerve entrapment (PNE) between the sacrospinous and sacrotuberous ligaments is the most frequent etiology. We describe the technical details, feasibility, and advantages of a laparoscopic approach in patients with PNE. METHODS: Consecutive patients (n = 27) with a diagnosis of PNE underwent LaPNDT with omental flap protection in an effort to prevent re-fibrosis around the nerve in the long term. The degree of pain and pain impact were evaluated pre- and postoperatively using the visual analog pain scale (VAS) and the Impact of Symptoms and Quality of Life. RESULTS: The mean (± standard deviation [SD]) follow-up of the 27 patients was 6.8 ± 4.2 months; 16 of the 27 were followed-up for more than 6 months. The mean (SD) operation time was 199.4 ± 36.1 (155-300) min, and the mean estimated blood loss was 39.7 ml. All patients were ambulated on the first postoperative day, and the mean (SD) hospitalization time was 2.1 ± 1.0 (1-6) days. The mean VAS scores of 27, 23, 16, and 6 patients were 1.5, 1.4, 1.6, and 2.0, postoperatively, at the first, third, sixth, and twelfth months (p < 0.0001). A more than reduction in VAS score (>80 %) was achieved in 13 of the 16 patients (81.2 %) who were followed-up for more than 6 months. CONCLUSIONS: LaPNDT seems a feasible surgical modality for cautiously selected patients with PNE. In addition, using an omental flap for protection of the nerve is one of the most important technical advantages of laparoscopy. As a minimally invasive surgery, the laparoscopic approach can be technically feasible, with its promising preliminary results in the treatment of PNE. With further analysis, in the future it may open new frontiers for pudendal nerve neuromodulation as a new treatment modality in some intractable functional problems of the genitourinary tract.

Skin-to-stone distance has no impact on outcomes of percutaneous nephrolithotomy.

OBJECTIVE: Skin-to-stone distance (SSD) is a stronger factor than body mass index in predicting the success of shock wave lithotripsy. We aimed to evaluate the impact of SSD on outcomes of percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: The medical records of 1,280 patients who had undergone PCNL between April 2007 and February 2012 were evaluated retrospectively. 192 patients who had had preoperative non-contrasted computed tomography and single renal access were included the study. According to this median SSD value, patients were divided into two groups: group 1 (SSD ≤94 mm) (n = 92) and group 2 (SSD >94 mm) (n = 90). The groups were compared according to operative and postoperative parameters. RESULTS: We found no significant differences between the two groups with regard to stone-free rate, operation time, fluoroscopy time, hospitalization time, visual analog score of pain, stone burden, transfusion rates and complication rates. On the other hand, the mean body mass index of group 1 was significantly lower than that of group 2 (p < 0.05). CONCLUSIONS: In this retrospective review of patients undergoing PCNL, we found that SSD has no impact on operative and postoperative outcomes. These results were in accordance with the safety of PCNL in obese patients.

Prototol for the Prospective Sample Collection for Cancer of Bladder (ProCaB) Trial by the Cancer of the Bladder Leuven (CaBLe) Consortium.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease categorized as low, intermediate, high, or very high risk, for which recurrence and progression rates and thus management strategies differ. Current molecular subclassification of bladder cancer (BC) is mainly based on data for muscle-invasive disease, with very few data for NMIBC. A more accurate classification system is needed for better stratification of NMIBC using multiomics and immunohistopathological molecular data alongside clinical data collected in a prospective cohort. ProCaB (Prospective Sample Collection for Cancer of Bladder) is a single-center non-interventional, prospective study recruiting all eligible patients diagnosed with BC in a tertiary center in the Flanders region of Belgium. Clinical data have been collected in a prospective registry since August 2013. Biosamples (blood, urine, and BC tissue) are collected from each patient at diagnosis and are stored at -80°C at BioBank UZ Leuven after appropriate processing according to the protocol. Multiomics (genomics, epigenetics, transcriptomics, proteomics, lipidomics, metabolomics) and immunohistopathology analyses will be performed on appropriate samples. The target is to enroll 300 patients over a 5-yr period, and all patients will be followed for 5 yr. The objective is to create a biobank of samples from patients diagnosed with BC for use in multiomics and immunohistopathological analyses. Results from these analyses, together with long-term clinical data, can be used for comprehensive multilayered molecular characterization of disease recurrence and progression in intermediate- and (very) high-risk NMIBC, identification of multibiomarker panels for better stratification, and identification of a patient subgroup that does not respond to bacillus Calmette-Guérin treatment. This trial is registered on ClinicalTrials.gov as NCT04167332.

Deciphering the molecular heterogeneity of intermediate- and (very-)high-risk non-muscle-invasive bladder cancer using multi-layered -omics studies.

Bladder cancer (BC) is the most common malignancy of the urinary tract. About 75% of all BC patients present with non-muscle-invasive BC (NMIBC), of which up to 70% will recur, and 15% will progress in stage and grade. As the recurrence and progression rates of NMIBC are strongly associated with some clinical and pathological factors, several risk stratification models have been developed to individually predict the short- and long-term risks of disease recurrence and progression. The NMIBC patients are stratified into four risk groups as low-, intermediate-, high-risk, and very high-risk by the European Association of Urology (EAU). Significant heterogeneity in terms of oncological outcomes and prognosis has been observed among NMIBC patients within the same EAU risk group, which has been partly attributed to the intrinsic heterogeneity of BC at the molecular level. Currently, we have a poor understanding of how to distinguish intermediate- and (very-)high-risk NMIBC with poor outcomes from those with a more benign disease course and lack predictive/prognostic tools that can specifically stratify them according to their pathologic and molecular properties. There is an unmet need for developing a more accurate scoring system that considers the treatment they receive after TURBT to enable their better stratification for further follow-up regimens and treatment selection, based also on a better response prediction to the treatment. Based on these facts, by employing a multi-layered -omics (namely, genomics, epigenetics, transcriptomics, proteomics, lipidomics, metabolomics) and immunohistopathology approach, we hypothesize to decipher molecular heterogeneity of intermediate- and (very-)high-risk NMIBC and to better stratify the patients with this disease. A combination of different -omics will provide a more detailed and multi-dimensional characterization of the tumor and represent the broad spectrum of NMIBC phenotypes, which will help to decipher the molecular heterogeneity of intermediate- and (very-)high-risk NMIBC. We think that this combinatorial multi-omics approach has the potential to improve the prediction of recurrence and progression with higher precision and to develop a molecular feature-based algorithm for stratifying the patients properly and guiding their therapeutic interventions in a personalized manner.

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.

Laparoscopic radical prostatectomy. Impact of the learning curve on positive surgical margins.

OBJECTIVES: The study was conducted to assess the incidence of positive surgical margins (PSMs ) in our series of laparoscopic radical prostatectomy (LRP ) performed by a fellowship trained surgeon in independent practice. METHODS: In this series, 300 patients underwent LRP by the same surgeon at our institution. The prospectively created records of all consecutive LRPs were reviewed. The patients were divided into three groups based on the time of surgery: group I included the first 100 cases;group II included the second 100 cases; and group III the last 100 cases. We compared the incidence rate and the location of PSMs among the groups. As additional variables, prostate-specific antigen (PSA ) level, biopsy/specimen Gleason score, clinical/pathological stage and pathologic tumor volume were also evaluated. RESULTS: Patient demographics and preoperative staging variables were comparable among the three groups, with no statistically significant differences among them. The PSM rates were 27%, 22% and 27% for groups I, II and III, respectively. The difference in overall PSM rates in the three groups was statistically insignificant (p: 0.966 ) . PSM rates decreased specifically at the posterolateral region and in pT3b stage with non/significant difference when comparing the first 100 patients to the last 100 patients. CONCLUSION: Pathologic surgical margin safety can be achieved with laparoscopic fellowship/training (LFT ) from the initial cases in independent practice.

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.