The clinical meaning of lymphovascular invasion: preoperative predictors and postoperative implications in prostate cancer - a retrospective study.

Introduction: Lymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI. Methods: We retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively. Results: Numerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001). Conclusion: Our findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, to reveal the association between LVI and the number of positive lymph nodes in pN+ patients.

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.

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.

Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer-Lateralization Concept.

BACKGROUND: Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. METHODS: Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). RESULTS: Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). CONCLUSIONS: Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

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.

Lymph Node Dissection in Testicular Cancer: The State of the Art and Future Perspectives.

PURPOSE OF REVIEW: This narrative review provides a comprehensive overview of the evolving role of retroperitoneal lymph node dissection (RPLND) in the management of testicular cancer (TC). It explores the significance of RPLND as both a diagnostic and therapeutic tool, highlighting its contribution to accurate staging, its impact on oncological outcomes, and its influence on subsequent treatment decisions. RECENT FINDINGS: RPLND serves as an essential diagnostic procedure, aiding in the precise assessment of lymph node involvement and guiding personalized treatment strategies. It has demonstrated therapeutic value, particularly in patients with specific risk factors and disease stages, contributing to improved oncological outcomes and survival rates. Recent studies have emphasized the importance of meticulous patient selection and nerve-sparing techniques to mitigate complications while optimizing outcomes. Additionally, modern imaging and surgical approaches have expanded the potential applications of RPLND. In the context of TC management, RPLND remains a valuable and evolving tool. Its dual role in staging and therapy underscores its relevance in contemporary urological practice. This review highlights the critical role of RPLND in enhancing patient care and shaping treatment strategies, emphasizing the need for further research to refine patient selection and surgical techniques.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

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.

Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.

PURPOSE OF REVIEW: This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS: Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.

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.

Artificial Intelligence in Urooncology: What We Have and What We Expect.

INTRODUCTION: Artificial intelligence is transforming healthcare by driving innovation, automation, and optimization across various fields of medicine. The aim of this study was to determine whether artificial intelligence (AI) techniques can be used in the diagnosis, treatment planning, and monitoring of urological cancers. METHODOLOGY: We conducted a thorough search for original and review articles published until 31 May 2022 in the PUBMED/Scopus database. Our search included several terms related to AI and urooncology. Articles were selected with the consensus of all authors. RESULTS: Several types of AI can be used in the medical field. The most common forms of AI are machine learning (ML), deep learning (DL), neural networks (NNs), natural language processing (NLP) systems, and computer vision. AI can improve various domains related to the management of urologic cancers, such as imaging, grading, and nodal staging. AI can also help identify appropriate diagnoses, treatment options, and even biomarkers. In the majority of these instances, AI is as accurate as or sometimes even superior to medical doctors. CONCLUSIONS: AI techniques have the potential to revolutionize the diagnosis, treatment, and monitoring of urologic cancers. The use of AI in urooncology care is expected to increase in the future, leading to improved patient outcomes and better overall management of these tumors.

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.

Diagnostic Value of the Sentinel Lymph Node Technique in Patients with Muscle-Invasive Bladder Cancer.

BACKGROUND: The optimal limits of the bilateral pelvic lymph node dissection (PLND) template in bladder cancer treatment remain controversial. This study aimed to investigate whether radio-guided sentinel node (SLN) detection is a reliable technique for the perioperative localisation of potential lymphatic metastasis during cystectomy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We studied 54 patients with pT2-pT4 MIBC who underwent cystectomy with extended PLND (ePLND) augmented by the SLN technique. The identification of SLN was performed by preoperative SPECT/CT hybrid lymphoscintigraphy using peritumoral injection of nanocolloid-Tc-99m, followed by intraoperative navigation with a handheld γ-probe. All nodal specimens were collected separately and then fixed in formalin, stained with haematoxylin and eosin, and examined by an experienced uropathologist. RESULTS: A total of 1414 LNs were resected and examined for the presence of metastases. The mean number of harvested LNs was 26 (range: 11-50) per patient. In 51 of 54 patients, 192 SLNs were resected. In addition, 20/192 (10.4%) SLNs were located outside of the ePLND area. Overall, 72 metastatic LNs (LN+) were found in 22 of 54 patients (40.7%) and in 24/192 SLNs (12.5%). The SLN technique detected LN+ in 14 of 22 (64%) patients. The SLNs were the only sites of metastasis (SLN+ = LN+) in 6 of 22 (27.3%) LN+ patients, including two cases with foci located in the pararectal region. The diagnostic values for the sensitivity, specificity, positive predictive value, and false-negative rate for the SLN technique were 66.66%, 4.16%, 28.57%, and 33.33%, respectively. Extended lymphadenectomy and its combination with the SLN technique enabled the correct assessment in 96.3 and 100% of patients, respectively. CONCLUSIONS: The combination of ePLND and SLN provides a better pN assessment compared to ePLND alone. Although the SLN technique has restrictions that limit its diagnostic value, its use as an addition to lymphadenectomy allows for the visualisation of nonstandard lymph drainage pathways that may be potential metastatic routes.

Sentinel Lymph Node Techniques in Urologic Oncology: Current Knowledge and Application.

Lymph node (LN) metastases have a significant negative impact on the prognosis of urological malignancies. Unfortunately, current imaging modalities are insufficient when it comes to detecting micrometastases; thus, surgical LN removal is commonly used. However, there is still no established ideal lymph node dissection (LND) template, leading to unnecessary invasive staging and the possibility of missing LN metastases located outside the standard template. To address this issue, the sentinel lymph node (SLN) concept has been proposed. This technique involves identifying and removing the first group of draining LNs, which can accurately stage cancer. While successful in breast cancer and melanoma, the SLN technique in urologic oncology is still considered experimental due to high false-negative rates and lack of data in prostate, bladder, and kidney cancer. Nevertheless, the development of new tracers, imaging modalities, and surgical techniques may improve the potential of the SLN procedures in urological oncology. In this review, we aim to discuss the current knowledge and future contributions of the SLN procedure in the management of urological malignancies.