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.

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.

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.

STAT3 and Its Pathways' Dysregulation-Underestimated Role in Urological Tumors.

Nowadays, molecular research is essential for the better understanding of tumor cells' pathophysiology. The increasing number of neoplasms is taken under 'the molecular magnifying glass'; therefore, it is possible to discover the complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs, which comprises seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration, and angiogenesis. Inhibition of this transcription factor inhibits the previously mentioned effects in cancer cells, whereas normal cells are not affected. Hence, STAT3 might be a viable target for cancer therapy.

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.

Patients with Positive Lymph Nodes after Radical Prostatectomy and Pelvic Lymphadenectomy-Do We Know the Proper Way of Management?

Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required.

The Impact of Primary Tumor Location on Long-Term Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) accounts for up to 10% of all urothelial neoplasms. Currently, various tumor-related factors are proposed to be of importance in UTUC prognostic models; however, the association of the primary UTUC location with oncological outcomes remains controversial. Thus, we sought to perform a systematic review and meta-analysis of the latest available evidence and assess the impact of primary tumor location on long-term oncological outcomes in patients with UTUC undergoing radical nephroureterectomy. MATERIALS AND METHODS: A computerized systematic literature search was conducted in October 2021 through the PubMed, Web of Science, Scopus, and Cochrane Library databases. The primary endpoint was cancer-specific survival (CSS), and the secondary endpoints were overall survival (OS) and disease-free survival (DFS). Effect measures for the analyzed outcomes were reported hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the total number of 16,836 UTUC in 17 included studies, 10,537 (62.6%) were renal pelvic tumors (RPTs), and 6299 (37.4%) were ureteral tumors (UTs). Pooled results indicated that patients with UT had significantly worse CSS (HR: 1.37, p < 0.001), OS (HR: 1.26, p = 0.003, and DFS (HR: 1.51, p < 0.001) compared to patients with RPT. Based on performed subgroup analyses, we identified different definitions of primary tumor location and geographical region as potential sources of heterogeneity. CONCLUSIONS: Ureteral location of UTUC is associated with significantly worse long-term oncological outcomes. Our results support the need for close follow-up and the consideration of perioperative chemotherapy in patients with UTUC located in the ureter. However, further prospective studies are needed to draw final conclusions.

Influence of Virtual Reality Devices on Pain and Anxiety in Patients Undergoing Cystoscopy Performed under Local Anaesthesia.

BACKGROUND: Bladder cancer is one of the most common malignancies. Its diagnosis is based on transurethral cystoscopy. Virtual reality (VR) is a three-dimensional world generated through the projection of images, the emission of sounds and other stimuli. VR has been proven to be a very effective "distractor" and, thus, a useful tool in managing pain. The aim of this study was to determine whether the use of VR sets is technically feasible during the cystoscopy and whether the use of VR devices would reduce the degree of ailments associated with the procedure; Methods: The study prospectively included both men and women who qualified for rigid cystoscopy due to both primary and follow-up diagnostics. The study group underwent rigid cystoscopy with the VR set and the control group underwent the procedure without the VR set. Patients enrolled in both groups were subjected to blood pressure, heart rate and saturation measurements before, during and after the procedure. Additionally, the patients were asked to describe the severity of fear, pain sensations and nausea associated with the procedure. Non-verbal pain manifestations were assessed using the adult adjusted Faces, Legs, Activity, Cry and Consolability (FLACC) scale; Results: The study population included 103 patients (74M/29F; mean age 64.4 years). Pain intensity differed significantly between the groups, reaching lower values in the VR group. In all analyzed subgroups the use of the VR set was associated with higher levels of nausea. The mean FLACC score reached higher values for patients without the VR set. Blood pressure as well as heart rate increased during the procedure and decreased afterwards. The increase in systolic blood pressure and pulse rate was statistically higher in the control group; Conclusions: This study confirmed that cystoscopy is associated with considerable preprocedural fear and severe pain. Blood pressure and heart rate rise significantly during the cystoscopy. VR sets can lower pain perception during cystoscopy, but they may cause moderate nausea.

Pain reduction methods during transurethral cystoscopy.

Transurethral cystoscopy (CS) is a common urological procedure, performed mostly for diagnostic but also for therapeutic purposes. Although CS is generally well tolerated, some patients describe the pain related to the procedure as high or even "unbearable". As a result, many patients fear and avoid both primary and/or follow-up cystoscopies. This may lead to uncontrolled progression of neoplastic disease. Therefore, it is crucial to maximally increase the comfort of the patient and to implement safe and effective analgesia before the procedure. Providing the patients with appropriate care during CS can encourage them to comply with diagnostic schedules and improve their prognosis. The aim of this review is to analyze the available literature on various methods of pain reduction during transurethral CS. The PubMed electronic database limited to English articles published until January 2021 was used in the process. Meta-analyses, systematic reviews, randomized controlled trials, clinical trials, prospective randomized studies, multicenter comparisons, reviews and retrospective comparisons were used. As a result, 65 articles were included in this review.

The Impact of Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND: The incidence of intravesical recurrence (IVR) following radical nephroureterectomy (RNU) is reported in up to 50% of patients with upper tract urothelial carcinoma (UTUC). It was suggested that preoperative diagnostic ureteroscopy (URS) could increase the IVR rate after RNU. However, the available data are often conflicting. Thus, in this systematic review and meta-analysis we sought to synthesize available data for the impact of pre-RNU URS for UTUC on IVR and other oncological outcomes. MATERIALS AND METHODS: A systematic literature search of the PubMed, Embase, and Cochrane Library databases was performed in June 2021. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CI) were conducted. The primary endpoint was intravesical recurrence-free survival (IVRFS), with the secondary endpoints being cancer-specific survival (CSS), overall survival (OS), and metastasis-free survival (MFS). RESULTS: Among a total of 5489 patients included in the sixteen selected papers, 2387 (43.4%) underwent diagnostic URS before RNU and 3102 (56.6%) did not. Pre-RNU diagnostic URS was significantly associated with worse IVRFS after RNU (HR = 1.44, 95% CI: 1.29-1.61, p < 0.001) than RNU alone. However, subgroup analysis including patients without biopsy during URS revealed no significant impact of diagnostic URS on IVRFS (HR = 1.28, 95% CI: 0.90-1.80, p = 0.16). The results of other analyses showed no significant differences in CSS (HR = 0.94, p = 0.63), OS (HR: 0.94, p = 0.56), and MFS (HR: 0.91, p = 0.37) between patients who underwent URS before RNU and those who did not. CONCLUSIONS: The results of this meta-analysis confirm that diagnostic URS prior to RNU is significantly associated with worse IVRFS, albeit with no concurrent impact on the other long-term survival outcomes. Our results indicate that URS has a negative impact on IVRFS only when combined with endoscopic biopsy. Future studies are warranted to assess the role of immediate postoperative intravesical chemotherapy in patients undergoing biopsy during URS for suspected UTUC.

Oncological outcomes of laparoscopic versus open nephroureterectomy for the treatment of upper tract urothelial carcinoma: an updated meta-analysis.

BACKGROUND: During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. MATERIALS AND METHODS: The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. RESULTS: Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60-1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62-1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85-1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94-1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. CONCLUSIONS: Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

Assessment of the oncological outcomes of three different bacillus Calmette-Guérin strains in patients with high-grade T1 non-muscle-invasive bladder cancer.

OBJECTIVE: : To determine whether there are significant differences in oncological outcomes between three different bacillus Calmette-Guérin (BCG) strains used for adjuvant intravesical immunotherapy in patients with high-grade T1 (T1HG) non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: : Data of 590 patients with a diagnosis of primary T1HG NMIBC were retrospectively reviewed. The study included 138 (23.4%) patients who were treated with the Moreau, 272 (46.1%) with the TICE, and 180 (30.5%) with the RIVM strains. All patients included in the analysis received at least five instillations of an induction course and at least two installations of a maintenance course. Due to existing differences in baseline patient characteristics, the association between oncological outcomes and strain groups was investigated by complementary analysis with the implementation of inverse probability weighting (IPW). RESULTS: : The 5-year recurrence-free survival (RFS) rate was 70.5%, 66.7% and 55.2% for the Moreau, TICE and RIVM groups, respectively (P = 0.016). The 5-year progression-free survival (PFS) rates were 84.4%, 85% and 77.8% in the Moreau, TICE and RIVM groups, respectively (P = 0.215). The IPW-adjusted Cox proportional hazard regression analysis did not show any differences in RFS between the Moreau and TICE groups (P = 0.69), whereas the RIVM strain was significantly associated with worse RFS compared to the Moreau (hazard ratio [HR] 1.69 for RIVM; P = 0.034) and TICE (HR 1.87 for RIVM; P = 0.002) strains. The IPW-adjusted analysis did not show any significant differences between study groups in terms of PFS. CONCLUSIONS: : The results of the present study suggest that the Moreau and TICE strains might be superior to the RIVM strain in terms of RFS in patients with T1HG NMIBC.Abbreviations: CIS: carcinoma in situ; IPW: inverse probability weighting; IQR: interquartile range; HR: hazard ratio; HG: high grade; LVI: lymphovascular invasion; MP: muscularis priopria; NMIBC: non-muscle-invasive bladder cancer; PFS: progression-free survival; RCT: randomised controlled trial; RFS: recurrence-free survival; T1HG, high-grade T1; (re-)TURB: (re-staging) transurethral resection of bladder; VH: variant histology.

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes.

PURPOSE: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette-Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The median TTBCG was 95 days (interquartile range (IQR): 71-127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. CONCLUSION: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression.

Urological complications after radiation therapy-nothing ventured, nothing gained: a Narrative Review.

Radiation therapy along with chemotherapy and surgery are the three main treatment modalities used in oncology. The main disadvantage of radiotherapy is the fact that it affects both cancer and healthy cells located in the tumour area. As a consequence, different complications develop. A large proportion of cancers treated with radiotherapy are located in the lower abdomen and pelvis, which is why complications often involve the urinary tract. Due to the anatomy of these areas, urological complications occur not only after radiological treatment of urological cancers, but also after treatment of malignancies of the reproductive or digestive system. The most common radiation-induced complications include haemorrhagic cystitis, urethral and ureteral strictures, urinary fistulae, and secondary primary malignancies. Adverse events significantly degrade the quality of life of the patient, and in severe cases can be life threatening to the patient. Because of impaired tissue healing, the treatment of radiation urological complications is a challenge for urologists and often requires complicated reconstruction techniques. Continuous increase in the effectiveness of cancer treatments and the extension of patients' lives, make complications of radiation therapy an increasingly common clinical problem. The aim of this review is to present the pathophysiology, clinical presentation and methods of treatment for radiation-induced urological complications.