Application of nitroxoline in urologic oncology - a review of evidence.

The persistence of high incidence and mortality rates associated with urologic cancers underscores the urgent need for effective and safe treatments. Conventional chemotherapy regimens are often limited by their high toxicity, the cancer's drug resistance, and the challenge of managing independently evolving multifocal spread. In this context, a repurposing strategy is particularly enticing. It allows for the introduction of a drug with a known safety profile, thus significantly reducing the costs and time necessary to introduce a new treatment. Nitroxoline (NIT), a drug with a well-established pharmacokinetic profile known for over 50 years and utilised in treating uncomplicated urinary tract infections, has recently garnered attention for its potential oncologic applications. Given the pharmacokinetic properties of NIT, our focus was specifically on urologic cancers in which its excretion profile is most advantageous. We examined all available studies, demonstrating significant effectiveness of NIT in inhibiting angiogenesis, tissue invasion, metastasis formation, and counteracting multidrug resistance. The efficacy and mechanism of action of NIT were found to vary across different cell lines. The findings to date are promising, suggesting that NIT or its derivatives could play a role in oncology, although further research is necessary to fully understand its potential and applicability in cancer treatment.

Retrograde intrarenal surgery using the ILY robotic flexible ureteroscope: a single centre experience.

Introduction: The ILY robotic flexible ureteroscope has been introduced in order to improve intraoperative ergonomics, reduce operator distance from radiation and shorten the learning curve. In this study we aimed to assess the clinical performance and feasibility of the ILY robot during retrograde intrarenal surgery (RIRS) and combined endoscopic procedures (miniECIRS). Material and methods: The RIRS procedures were performed using the ILY robotic arm in 57 adult patients (46 RIRS and 11 miniECIRS) from 2022 to 2023. All procedures were performed in the supine position. Pre-stenting was not the standard of care. Results: Turning on and calibration of the device took approximately 100 s. Average draping time was 93 s using original ILY drapes and 47 s using classic drapes designed for C-arm covering. Mean docking time was 73 s in procedures with ureteral access sheath (UAS) and 61 s in procedures without it. The undocking took less than 60 s in every case. Average procedure time was 63 min for RIRS and 55 min for miniECIRS. Endoscopically proven stone-free rate was achieved in 37 (80.4%) RIRS and 10 (90.9%) miniECIRS patients. A total of 17 (36.9%) RIRS and 8 (72.7%) miniECIRS procedures required conversion in order to perform basketing and stone fragments retrieval/transposition. Conclusions: The use of ILY robot during endourological procedures is feasible and urologists that are familiar with the device controller do not require extensive training. The time needed for device draping, docking and undocking was approximately 4 minutes. Moreover, use of the robot resulted in satisfactory stone-free rates.

Clinical and Oncological Outcomes Following Percutaneous Cryoablation vs. Partial Nephrectomy for Clinical T1 Renal Tumours: Systematic Review and Meta-Analysis.

Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN.

The Impact of Venous Thromboembolism on Upper Tract Urothelial Carcinomas Undergoing Open or Minimally Invasive Radical Nephroureterectomy in the USA: Perioperative Outcomes and Health Care Costs from Insurance Claims Data.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context. METHODS: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined. KEY FINDINGS AND LIMITATIONS: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging. CONCLUSIONS AND CLINICAL IMPLICATIONS: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting. PATIENT SUMMARY: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE.

Preoperative Factors for Lymphovascular Invasion in Prostate Cancer: A Systematic Review and Meta-Analysis.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical recurrence (BCR), and lymph node metastasis (LNM). The ability to predict LVI preoperatively in PCa may be useful for proposing variations in the diagnosis and management strategies. We performed a systematic review and meta-analysis to identify preoperative clinicopathological factors that correlate with LVI in final histopathological specimens in PCa patients. Systematic literature searches of PubMed, Embase, and Web of Science were performed up to 31 January 2023. A total of thirty-nine studies including 389,918 patients were included, most of which were retrospective and single-center. PSA level, clinical T stage, and biopsy Gleason score were significantly correlated with LVI in PCa specimens. Meta-analyses revealed that these factors were the strongest predictors of LVI in PCa patients. Prostate volume, BMI, and age were not significant predictors of LVI. A multitude of preoperative factors correlate with LVI in final histopathology. Meta-analyses confirmed correlation of LVI in final histopathology with higher preoperative PSA, clinical T stage, and biopsy Gleason score. This study implies advancements in risk stratification and enhanced clinical decision-making, and it underscores the importance of future research dedicated to validation and exploration of contemporary risk factors in PCa.

Is the Urinary and Gut Microbiome Associated With Bladder Cancer?

Background: Microbiome dysbiosis plays a role in the pathogenesis of many urological diseases, including bladder cancer (BC). The aim of the study was to compare the urinary and gut microbiota of patients with BC with a healthy control (HC) group. Methods: The study group included patients hospitalized in 2020 to 2021 with diagnosed BC and HC. Prior to the transurethral resection of bladder tumor, patients collected their urine and stool which was then subjected to 16S rRNA gene sequencing. Results: Overall, 25 patients were enrolled in the study: 18 in the BC group and 7 in the HC group. Analysis of the urine and stool microbiome showed no statistically significant differences between patients with BC and HC in alpha diversity, beta diversity, and difference in taxa relative abundance. Detailed analysis of urine and stool microbiome depending on patient- and tumor-related characteristics also showed no statistically significant differences in alpha diversity and beta diversity. Differences in abundance (ANCOM) were noted in both types of samples in patients with BC. In the urine test, genus Lactobacillus was more common in patients with a positive history of Bacillus Calmette-Guérin (BCG) therapy, while genus Howardella and the strain Streptococcus anginosus were more common in women. In stool samples, abundance of phylum Desulfobacterota was most abundant in Grade G1 and least in G2. Class Alphaproteobacteria, order Rhodospirillales, order Flavobacteriales, and family Flavobacteriaceae were more common in women. Conclusions: The microbiome of urine and stool of patients with BC does not differ significantly from that of HC; however, its composition in patients with BC varies according to the patient's sex.

Comparative analysis of GOLPH3 expression in lymph node-positive prostate cancer: immunohistochemistry staining patterns and clinical significance.

Introduction: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression. Methods: The study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed. Results: A positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP - the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05). Conclusion: GOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes.

Urinary Microbiome in Bladder Diseases-Review.

The microbiome is the totality of microorganisms found in a specific biological niche. It has been proven that in the human body, the microbiome is responsible for its proper functioning. Dysbiosis, i.e., a disturbance in the composition of the microbiome, may be associated with the pathogenesis of many human diseases. Until recently, studies did not focus on the microbiome of the urinary tract, because, since the 19th century, there had been a dogma that urine in healthy people is sterile. Yet, advances in molecular biology techniques have allowed this dogma to be overthrown. The use of DNA sequencing has shown that the urinary tract has its own endogenous microbiome. This discovery enabled further research on the characteristics of the urine microbiomes of healthy people, as well as on the role of the urine microbiome in the pathogenesis of many urological diseases, including bladder diseases. The aim of this review is to summarize the current knowledge on the urinary microbiome in bladder diseases and to identify potential directions for further research.

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.

Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found-expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.

Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis.

BACKGROUND: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. METHODS: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. RESULTS: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. CONCLUSION: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models.

BACKGROUND: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential therapeutic agent against bladder cancer (BC). Also, we aimed to determine whether Degrasyn is more effective in terms of anti-cancer activity compared to the non-selective DUB inhibitor PR-619. To facilitate the translational value of the obtained results, our experiments were performed using both human and canine in vitro models of BC. METHODS: Human T24 (urothelial grade III BC) and SV-HUC-1 (non-tumorigenic urothelial cell line), as well as canine K9TCC-PU-NK and RDSVS-TCC1 (both derived from invasive grade III urothelial bladder tumors) cell lines, were used in the present study. Cell proliferation was determined using the MTT assay and Ki-67 proliferation assay, and the level of apoptosis induced by Degrasyn and PR-619 was evaluated by Annexin V-FITC staining and caspase 3/7 activation assay. Western blot was used to assess DNA damage and key proteins involved in apoptosis. RESULTS: Degrasyn inhibited the proliferation of all BC cell lines in a concentration- and time-dependent manner. Lower concentrations of Degrasyn were more potent against human and canine BC cell lines compared to PR-619. Degrasyn induced caspase-dependent apoptosis and triggered DNA damage. PR-619 did not show a significant pro-apoptotic effect. CONCLUSIONS: Our results demonstrate that Degrasyn significantly impairs the growth of in vitro models of human and canine BC. Selective USP inhibition with Degrasyn seems to be more effective in reducing BC cell proliferation and inducing apoptosis and DNA damage than non-selective USP inhibition with PR-619.

Current methods facilitating diagnosis of upper tract urothelial carcinoma: a comprehensive literature review.

PURPOSE OF REVIEW: Currently, kidney-sparing surgeries are considered the preferred approach in low-risk tumours and in selected high-risk patients. Therefore, accurate diagnosis of UTUC is crucial for further management. The purpose of this review is to summarize available methods facilitating the diagnosis of upper tract urothelial carcinoma (UTUC). RECENT FINDINGS: Recent articles propose numerous techniques of UTUC diagnosis. In this review, imaging, as well as, urine-based and endoscopic methods have been described and assessed. SUMMARY: Regarding imaging, computed tomography urography remains a gold standard, while PET is superior in search for small lesions and nodal metastases. However, contrast-enhanced ultrasonography also shows promise. On the contrary, available urine tests, such as urinary cytology, fluorescent in-situ hybridization, Xpert, DNA methylation analysis, urine-based liquid biopsy, p16/Ki-67 dual immunolabelling, ImmunoCyt and NMP22 are either poorly researched, or not accurate enough to use solely. Finally, during ureterorenoscopy, photodynamic diagnosis and narrow-band imaging can facilitate proper visualization of the tumor. Endoluminal ultrasonography and confocal laser endomicroscopy can potentially improve staging and grading of UTUC. Also, the 'form tackle' biopsy should be performed using a basket in papillary lesions and cold-cup biopsy of flat or sessile lesions. Even though cryobiopsy shows promise in UTUC diagnosis, in-vivo studies are necessary before it is introduced into clinical practice.

Interleukin 17 and Its Involvement in Renal Cell Carcinoma.

Nowadays, molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms has been taken under 'the molecular magnifying glass' and, therefore, it is possible to discover complex relationships between the cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17)-an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancers because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relationship with tumors is extremely complex and constitutes a recent topic for numerous studies. What is worth highlighting is IL-17's dual character in cancer development-it could be pro- as well as anti-tumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.

Assessment of Preoperative TSH Serum Level and Thyroid Cancer Occurrence in Patients with AUS/FLUS Thyroid Nodule Diagnosis.

Thyroid-stimulating hormone (TSH) is a growth factor associated with the initiation and progression of well-differentiated thyroid cancer (WDTC). Atypia of undetermined significance and follicular lesion of undetermined significance (AUS/FLUS) are the most uncertain cytological diagnoses of thyroid nodules. The aim of the study was to determine the association of histopathological diagnosis with preoperative serum TSH levels in patients with AUS/FLUS thyroid nodule diagnosis. Among 5028 individuals with thyroid nodules, 342 (6.8%) with AUS/FLUS diagnoses were analyzed. The frequency of all histopathology diagnoses was assessed for associations with preoperative serum TSH levels. The median TSH concentration was significantly higher in patients with AUS/FLUS diagnosis and histopathology of WDTC than in patients with the same cytology result and histopathology of a benign tumor (p < 0.0001). The diagnostic potential of serum TSH level was determined to evaluate risk of malignancy in patients with thyroid nodules classified into the Bethesda III category. ROC analysis showed the TSH concentration at a cutoff point of 2.5 mIU/L to be an acceptable prognostic factor for WDTC. For this optimal cutoff point, the AUC was 0.877, the sensitivity was 0.830, and the specificity was 0.902. Preoperative serum TSH levels in patients with AUS/FLUS thyroid tumor diagnosis should be taken into consideration in the decision-making process and clinical management.

The Impact of Surgical Waiting Time on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy: A Systematic Review.

Radical nephroureterectomy (RNU) with bladder cuff excision is a standard of care in patients with high-risk upper tract urothelial carcinoma (UTUC). Although several recommendations and guidelines on the delayed treatment of urologic cancers exist, the evidence on UTUC is scarce and ambiguous. The present systematic review aimed to summarize the available evidence on the survival outcomes after deferred RNU in patients with UTUC. A systematic literature search of the three electronic databases (PubMed, Embase, and Cochrane Library) was conducted until 30 April 2022. Studies were found eligible if they reported the oncological outcomes of patients treated with deferred RNU compared to the control group, including those patients treated with RNU without delay. Primary endpoints were cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In total, we identified seven eligible studies enrolling 5639 patients. Significant heterogeneity in the definition of "deferred RNU" was found across the included studies. Three out of five studies reporting CSS showed that deferring RNU was associated with worse CSS. Furthermore, three out of four studies reporting OS found a negative impact of delay in RNU on OS. One out of three studies reporting RFS found a negative influence of delayed RNU on RFS. While most studies reported a 3 month interval as a significant threshold for RNU delay, some subgroup analyses showed that a safe delay for RNU was less than 1 month in patients with ureteral tumors (UT) or less than 2 months in patients with hydronephrosis. In conclusion, long surgical waiting time for RNU (especially more than 3 months after UTUC diagnosis) could be considered as an important risk factor having a negative impact on oncological outcomes in patients with UTUC; however, the results of the particular studies are still inconsistent. The safe delay for RNU might be shorter in specific subsets of high-risk patients, such as those with UT and/or hydronephrosis at the time of diagnosis. High-quality additional studies are required to establish evidence for valid recommendations.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Utility of Lymphadenectomy in Prostate Cancer: Where Do We Stand?

The purpose of this review is to summarize the current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, the utility and therapeutic and prognostic value of such an approach, as well as the optimal extent of LND, remain unsolved issues. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature, which limits the possibility of establishing clear recommendations. This indicates the need for further robust and adequately designed high-quality clinical trials.