Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

BACKGROUND: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. RESULTS: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). CONCLUSIONS: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Changes in the Urinary Microbiome After Transurethral Resection of Non-muscle-Invasive Bladder Cancer: Insights from a Prospective Observational Study.

BACKGROUND: This study aimed to characterize the urinary and tumor microbiomes in patients with non-muscle-invasive bladder cancer (NMIBC) before and after transurethral resection of the bladder tumor (TURBT). METHODS: This single-center prospective study included 26 samples from 11 patients with low-grade Ta papillary NMIBC. Urine samples were collected at the index TURBT and at a 1-year follow-up cystoscopy. The metagenomic analysis of bacterial and archaeal populations was performed based on the highly variable V3-V4 region of the 16S rRNA gene. RESULTS: Phylogenetic alpha diversity of the bladder microbiome detected in urine was found to be lower at the 1-year follow-up cystoscopy compared to the time of the index TURBT (p < 0.01). Actinomyces, Candidatus cloacimonas, Sphingobacterium, Sellimonas, Fusobacterium, and Roseobacter were more differentially enriched taxa in urine at the follow-up cystoscopy than at the index TURBT. Beta diversity of urine microbiome significantly changed over time (p < 0.05). Phylogenetic alpha diversity of the microbiome was greater in tumor tissues than in paired urine samples (p<0.01). Sphingomonas, Acinetobacter, Candidatus, and Kocuria were more differentially overrepresented in tumor tissues than in urine. The enrichment of the abundance of Corynebacterium and Anaerococcus species in urine collected at TURBT was observed in patients who experienced recurrence within the follow-up period. CONCLUSIONS: In patients with low-grade NMIBC, the urine microbiome undergoes changes over time after removal of the tumor. The microbiome detected in tumor tissues is more phylogenetically diverse than in paired urine samples collected at TURBT. The interplay between bladder microbiome, tumor microbiome, and their alterations requires further studies to elucidate their predictive value and perhaps therapeutic implications.

Cancer-Specific Survival of Patients with Non-Muscle-Invasive Bladder Cancer: A Population-Based Analysis.

BACKGROUND AND PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) constitutes a heterogeneous group of tumors with different prognoses. This population-based study aimed to report real-world cancer-specific survival (CSS) of NMIBC and create a prognostic nomogram based on the identified risk factors. METHODS: The Surveillance, Epidemiology, and End Results database was searched for patients diagnosed with NMIBC from 2004 to 2015, who underwent transurethral resection of the bladder tumor. The dataset was divided into development and validation cohorts. Factors associated with CSS were identified using Cox proportional hazards and used to develop a prognostic nomogram. RESULTS: In total, 98,238 patients with NMIBC were included. At the median follow-up of 124 months (IQR 81-157 months), cancer-specific mortality (CSM) was highest for T1HG (19.52%), followed by Tis (15.56%), similar for T1LG and TaHG (10.88% and 9.23%, respectively), and lowest for TaLG (3.76%). Multivariable Cox regression for CSS prediction was utilized to develop a nomogram including the following risk factors: tumor T category and grade, age, tumor size and location, histology type, primary character, race, income, and marital status. In the validation cohort, the model was characterized by an AUC of 0.824 and C-index that reached 0.795. CONCLUSIONS: To conclude, NMIBC is associated with a significant risk of long-term CSM especially, but not only, in patients with T1HG. Rarely diagnosed TaHG and T1LG tumors should be regarded as high-risk due to approximately 10% CSM. T category, grading, and age remain the most powerful determinants of CSS in NMIBC, but sociodemographic factors might also influence its prognosis.

Magnetic resonance imaging (MRI) for local staging before salvage radical prostatectomy: a meta-analysis.

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.

The Cannabinoid Ligand Arachidonyl-2'-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model.

There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2'-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I-control, II-received CORT, III-received ACEA, and IV-received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-α, IL-1ß and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.

The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms.

Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1ß, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T-H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern.

BACKGROUND: Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed. METHODS: All patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994-1996, 2004-2006, and 2011-2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria. RESULTS: Bacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004-2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90-95%) and its efficacy was even improved by adding vancomycin (97-98%). CONCLUSIONS: Substantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

Patterns of care in patients with muscle-invasive bladder cancer - a retrospective cohort study.

A potential reason for poor survival among patients with muscle-invasive bladder cancer (MIBC) in Poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status. The aim of this study was to describe patterns of care in patients with newly diagnosed MIBC. This is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed MIBC. Therapeutic decisions and potentially underlying clinical factors were analysed. Full clinical data was available for 285 patients. One hundred and sixty-four (57.5%) patients were qualified for radical cystectomy (RC), 32 (11.2%) patients for a second step of transurethral resection of the bladder tumour (TURBT) intentionally followed by systemic chemotherapy, four (1.4%) patients after complete TURBT were qualified for adjuvant intravesical chemotherapy only, while the remaining 85 (29.8%) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care. Patients disqualified from curative treatment were older (78 vs. 69 years, p < 0.02), had lower BMI values (24.5 vs. 25.7 kg/m(2), p < 0.02), lower haemoglobin concentration (11.6 vs. 12.9 mg/l, p < 0.02), declared lower rate of nicotine abuse (50.5% vs. 72.1%, p < 0.02), and had a shorter time interval between first symptom and diagnosis (30 vs. 60 days, p = 0.02). As the majority of Polish patients with primary MIBC receive curative treatment, the stage of the disease alone seems not to be the leading cause of poor survival. However, appropriateness of qualification for RC and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in Poland.

Interobserver variability of Clavien-Dindo scoring in urology.

OBJECTIVES: To assess the interobserver variability of Clavien-Dindo scoring in urology. METHODS: A thematic survey was carried out simultaneously in nine Polish urological centers among 171 responders - 81 urologists and 90 urologists-in-training, made up of 16 women and 155 men. After Clavien-Dindo classification was presented, respondents were asked to grade nine typical urological complications according to Clavien-Dindo classification. Interobserver agreement, reproducibility of answers, as well as the influencing factors were analyzed. Questions in the survey related to complications of variable severity after basic urological operations, including four open, one laparoscopic and four endourological. RESULTS: Agreement on the grade of complication was moderate (κ = 0.45) and it was noticed in 69% of respondents (range 38-87%). No effect of surgical approach (classic vs endoscopic, 70% vs 67%, P = 0.64), or physician professional experience (resident vs urologist, 71% vs 66%, P = 0.77) was observed. The most significant discrepancies were found in cases of local complications after transurethral surgery (accordance in 39%) and laparoscopic radical prostatectomy (accordance in 55%), and in cases of severe general complications after Bricker operation (accordance in 58%). CONCLUSIONS: The variability of Clavien-Dindo classification scoring among urologists is significant. Thus, the Clavien-Dindo classification might require detailing before its eventual implementation in urology, together with appropriate training of specialists. However, despite some disadvantages, the simplicity, reproducibility and logical scheme of the Clavien-Dindo classification make it a promising tool for quality assessment in different fields of urology.

Advances in the Treatment of Kidney and Upper Urinary Tract Cancers.

Kidney and upper tract urinary cancers (UTUC) are diseases of increasing population coverage, the treatment of which is undergoing a continuous process of evolution [...].

Assessing the Predictive Accuracy of EORTC, CUETO and EAU Risk Stratification Models for High-Grade Recurrence and Progression after Bacillus Calmette-Guérin Therapy in Non-Muscle-Invasive Bladder Cancer.

The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette-Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.

Oncologic outcomes of patients treated with kidney-sparing surgery or radical nephroureterectomy for upper urinary tract urothelial cancer: a population-based study.

PURPOSE: Although kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. METHODS: We searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. RESULTS: The study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). CONCLUSION: In this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS.

(A)voiding misdiagnosis: prediction of detrusor underactivity vs. bladder outlet obstruction using pre-urodynamic nomogram in male patients with LUTS.

PURPOSE: Our study aimed to develop a noninvasive model using a combination of the set of clinical data and uroflowmetry (UFL) to differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO) in non-neurogenic male patients with lower urinary tract symptoms (LUTS). METHODS: Data from 229 men with LUTS, diagnosed with DU or BOO on a pressure-flow study (PFS), were retrospectively analyzed, including medical history, Core Lower Urinary Tract Symptoms score (CLSS) questionnaire, UFL and PFS. Uni- and multivariate logistic regression were utilized for the prediction analyses. RESULTS: Of the cohort, 128 (55.9%) patients were diagnosed with DU. A multivariate logistic regression analysis identified less prevalent nocturia (OR 0.27, p < 0.002), more prevalent intermittency (OR 2.33, p = 0.03), less prevalent weak stream (OR 0.14, p = 0.0004), lower straining points in CLSS (OR 0.67, p = 0.02), higher slow stream points in CLSS (OR 1.81, p = 0.002), higher incomplete emptying points in CLSS (OR 1.31, p < 0.02), lower PVR ratio (OR 0.20, p = 0.03), and present features of fluctuating (OR 2.00, p = 0.05), fluctuating-intermittent (OR 3.09, p < 0.006), and intermittent (OR 8.11, p = 0.076) UFL curve shapes as independent predictors of DU. The above prediction model demonstrated satisfactory accuracy (c-index of 0.783). CONCLUSION: Our 10-factor model provides a noninvasive approach to differentiate DU from BOO in male patients with non-neurogenic LUTS, offering a valuable alternative to invasive PFS.

Can We Go beyond Pathology? The Prognostic Role of Risk Scoring Tools for Cancer-Specific Survival of Patients with Bladder Cancer Undergoing Radical Cystectomy.

Radical cystectomy (RC) remains a mainstay surgical treatment for non-metastatic muscle-invasive and BCG-unresponsive bladder cancer. Various perioperative scoring tools assess comorbidity burden, complication risks, and cancer-specific mortality (CSM) risk. We investigated the prognostic value of these scores in patients who underwent RC between 2015 and 2021. Cox proportional hazards were used in survival analyses. Risk models' accuracy was assessed with the concordance index (C-index) and area under the curve. Among 215 included RC patients, 63 (29.3%) died, including 53 (24.7%) cancer-specific deaths, with a median follow-up of 39 months. The AJCC system, COBRA score, and Charlson comorbidity index (CCI) predicted CSM with low accuracy (C-index: 0.66, 0.65; 0.59, respectively). Multivariable Cox regression identified the AJCC system and CCI > 5 as significant CSM predictors. Additional factors included the extent of lymph node dissection, histology, smoking, presence of concomitant CIS, and neutrophil-to-lymphocyte ratio, and model accuracy was high (C-index: 0.80). The internal validation of the model with bootstrap samples revealed its slight optimism of 0.06. In conclusion, the accuracy of the AJCC staging system in the prediction of CSM is low and can be improved with the inclusion of other pathological data, CCI, smoking history and inflammatory indices.

Role of Lutetium Radioligand Therapy in Prostate Cancer.

Theranostics utilize ligands that chelate radionuclides and selectively bind with cancer-specific membrane antigens. In the case of prostate cancer (PCa), the state-of-the-art lutetium-177-PSMA combines the radioactive ß-emitter 177Lu with Vipivotide Tetraxetan, a prostate-specific membrane antigen (PSMA)-binding ligand. Several studies have been conducted, and the therapy is not without adverse effects (e.g., xerostomia, nausea, and fatigue); however, few events are reported as severe. The available evidence supports the use of 177Lu-PSMA in selected metastatic castration-resistant prostate cancer patients, and the treatment is considered a standard of care in several clinical scenarios. Emerging research shows promising results in the setting of hormone-sensitive prostate cancer; however, evidence from high-quality controlled trials is still missing. In this review, we discuss the available evidence for the application of 177Lu-PSMA in the management of PCa patients.

Management of Lymph Node-positive Penile Cancer: A Systematic Review.

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.

The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVES: Although smoking is a well-recognized causative factor of urothelial bladder cancer and accounts for 50% of cases, less is known about the prognostic significance of smoking on non-muscle invasive bladder cancer (NMIBC) prognosis. This systematic review and meta-analysis aimed to evaluate the effect of smoking on the risk of NMIBC recurrence and progression. MATERIALS AND METHODS: We systematically searched Medline, Web of Science and Scopus databases for original articles published before October 2021 regarding the effect of smoking on NMIBC recurrence and progression. Information about smoking status and the number of events or odds ratio or hazard ratio for event-free survival must have been reported to include the study in the analysis. Quality In Prognosis Studies tool was utilized for the risk of bias assessment. RESULTS: We selected 64 eligible studies, including 28 617 patients with NMIBC with available data on smoking status. In a meta-analysis of 28 studies with 7885 patients, we found that smokers (current/former) were at higher risk for recurrence (OR = 1.68; 95% CI 1.34-2.09; P < 0.0001) compared to never smokers. Subgroup analysis of 2967 patients revealed that current smokers were at a 1.24 higher risk of recurrence (OR = 1.24; 95% CI 1.02-1.50; P = 0.03) compared to former smokers. A meta-analysis of the hazard ratio revealed that smokers are at higher risk of recurrence (HR = 1.31; 95%CI 1.15-1.48; P < 0.0001) and progression (HR = 1.18; 95%CI 1.08-1.29; P < 0.001) compared to never smokers. Detrimental prognostic effect of smoking on progression, but not for recurrence risk was also noted in the subgroup analysis of high-risk patients (HR = 1.30; 95%CI 1.09-1.55; P = 0.004) and BCG-treated ones (HR = 1.15; 95%CI 1.06-1.25; P < 0.001). CONCLUSION: In conclusion, patients with non-muscle invasive bladder cancer and a history of smoking have a worse prognosis regarding recurrence-free and progression-free survival compared to non-smokers.