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.

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.

(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.

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.

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 [...].

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.

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.

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.

Systematic Review and Meta-analysis of Minimally Invasive Procedures for Surgical Inguinal Nodal Staging in Penile Carcinoma.

CONTEXT: There are several procedures for surgical nodal staging in clinically node-negative (cN0) penile carcinoma. OBJECTIVE: To evaluate the diagnostic accuracy, perioperative outcomes, and complications of minimally invasive surgical procedures for nodal staging in penile carcinoma. EVIDENCE ACQUISITION: A systematic review of the Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov was conducted. Published and ongoing studies reporting on the management of cN0 penile cancer were included without any design restriction. Outcomes included the false negative (FN) rate, the number of nodes removed, surgical time, and postoperative complications. EVIDENCE SYNTHESIS: Forty-one studies were eligible for inclusion. Four studies comparing robot-assisted (RA-VEIL) and video-endoscopic inguinal lymphadenectomy (VEIL) to open inguinal lymph node dissection (ILND) were suitable for meta-analysis. A descriptive synthesis was performed for single-arm studies on modified open ILND, dynamic sentinel node biopsy (DSNB) with and without preoperative inguinal ultrasound (US), and fine-needle aspiration cytology (FNAC). DSNB with US + FNAC had lower FN rates (3.5-22% vs 0-42.9%) and complication rates (Clavien Dindo grade I-II: 1.1-20% vs 2.9-11.9%; grade III-V: 0-6.8% vs 0-9.4%) in comparison to DSNB alone. Favourable results were observed for VEIL/RA-VEIL over open ILND in terms of major complications (2-10.6% vs 6.9-40.6%; odds ratio [OR] 0.18; p < 0.01). Overall, VEIL/RA-VEIL had lower wound-related complication rates (OR 0.14; p < 0.01), including wound infections (OR 0.229; p < 0.01) and skin necrosis (OR 0.16; p < 0.01). The incidence of lymphatic complications varied between 20.6% and 49%. CONCLUSIONS: Of all the surgical staging options, DSNB with inguinal US + FNAC had the lowest complication rates and high diagnostic accuracy, especially when performed in high-volume centres. If DSNB is not available, favourable results were also found for VEIL/RA-VEIL over open ILND. Lymphatic-related complications were comparable across open and video-endoscopic ILND. PATIENT SUMMARY: We reviewed studies on different surgical approaches for assessing lymph node involvement in cases with penile cancer. The results show that a technique called dynamic sentinel node biopsy with ultrasound guidance and fine-needle sampling has high diagnostic accuracy and low complication rates. For lymph node dissection in penile cancer cases, a minimally invasive approach may offer favourable postoperative outcomes.

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.

Prostate Cancer in Transplant Receivers-A Narrative Review on Oncological Outcomes.

Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population.

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.

Efficacy of Fractional CO2 Laser Treatment for Genitourinary Syndrome of Menopause in Short-Term Evaluation-Preliminary Study.

The postmenopausal state covers 40% of modern women's lives and 50-70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent inflammations, lack of elasticity, or dyspareunia. Consequently, a safe and effective method of treatment is crucial. In a group of 125 patients, a prospective observational study was performed. The aim was to evaluate the clinical effectiveness of fractional CO2 laser in the treatment of GSM symptoms using a protocol of three procedures in 6-week intervals. The vaginal pH, VHIS, VMI, FSFI, and treatment satisfaction questionnaire were used. The fractional CO2 laser treatment was effective in improving all the objective forms of evaluation: vaginal pH (from 5.61 ± 0.50 at the baseline up to 4.69 ± 0.21 in the 6-week follow-up after the third procedure); VHIS (12.02 ± 1.89 at the baseline vs. 21.50 ± 1.76); VMI (21.5 ± 5.66 vs. 48.4 ± 4.46). Similar results were obtained for FSFI: 12.79 ± 5.351 vs. 24.39 ± 2.733, where 79.77% of patients were highly satisfied. Fractional CO2 laser therapy increases the quality of life by having a beneficial effect on the sexual function of women with GSM symptoms. This effect is obtained by restoring the correct structure and proportions of the cellular composition of the vaginal epithelium. This positive effect was confirmed by both objective and subjective forms of evaluating GSM symptom severity.

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.

Telemedicine in Urology: Where Have We Been and Where Are We Heading?

Context: Humanity is facing significant challenges, and in 2019, a new coronavirus caused an unprecedented global disease outbreak. The coronavirus disease 2019 (COVID-19) pandemic vastly impacted health care delivery, generating devastating economic, social, and public health disruption. Although previously underutilized, it was not until recently that telemedicine emerged and amassed tremendous popularity. Objective: To examine and assess telemedicine's past, present, and future roles in urology. Evidence acquisition: We queried relevant literature investigating the role of telemedicine in urology using the electronic PubMed database and mainly focused on English-language studies of any design. Evidence synthesis: Growing attention has been paid to the widespread adoption of novel telehealth technologies for managing various diseases. Meanwhile, solid evidence supports the meaningful use of telemedicine for most urological diagnoses. Existing literature delineates telemedicine as a viable, safe, and convenient alternative to in-person clinical visits. Conclusions: The present article overviews the evolution of telemedicine in urology, and discusses its application in outpatient and physician's office settings. In addition, it highlights the technical, legal, ethical, and financial aspects of telemedicine while providing valuable insights and practical considerations for the future of telehealth in urology. Patient summary: Urologists must adopt telemedicine carefully in daily practice, always adhering to predefined regulatory frameworks.

European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update.

CONTEXT: Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines. OBJECTIVE: To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer. EVIDENCE ACQUISITION: Comprehensive literature searches were performed for each section topic. In addition, three systematic reviews were conducted. Levels of evidence were assessed, and a strength rating for each recommendation was assigned according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. EVIDENCE SYNTHESIS: Penile cancer is a rare disease but its global incidence is increasing. Human papillomavirus (HPV) is the main risk factor for penile cancer and pathology should include an assessment of HPV status. The main aim of primary tumour treatment is complete tumour eradication, which has to be balanced against optimal organ preservation without compromising oncological control. Early detection and treatment of lymph node (LN) metastasis is the main determinant of survival. Surgical LN staging with sentinel node biopsy is recommended for patients with a high-risk (≥pT1b) tumour with cN0 status. While (inguinal) LN dissection remains the standard for node-positive disease, multimodal treatment is needed in patients with advanced disease. Owing to a lack of controlled trials and large series, the levels of evidence and grades of recommendation are low in comparison to those for more common diseases. CONCLUSIONS: This collaborative penile cancer guideline provides updated information on the diagnosis and treatment of penile cancer for use in clinical practice. Organ-preserving surgery should be offered for treatment of the primary tumour when feasible. Adequate and timely LN management remains a challenge, especially in advanced disease stages. Referral to centres of expertise is recommended. PATIENT SUMMARY: Penile cancer is a rare disease that significantly impacts quality of life. While the disease can be cured in most cases without lymph node involvement, management of advanced disease remains challenging. Many unmet needs and unanswered questions remain, underlining the importance of research collaborations and centralisation of penile cancer services.

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.