EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2024 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.

CONTEXT: The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. OBJECTIVE: To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. EVIDENCE ACQUISITION: A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. EVIDENCE SYNTHESIS: We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. CONCLUSIONS: Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. PATIENT SUMMARY: We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.

[Usefulness of the g8 questionnaire in predicting frailty in elderly patients with metastatic or castration-resistant prostate cancer.] / Utilidad de cuestionario G8 en la predicción de fragilidad en pacientes ancianos con cáncer de próstata metastásico o resistente a castración.

OBJECTIVE: to assess the capacityof the G8 questionnaire for the detection of frailty inpatients over 75 years of age with metastatic or castrationresistant prostate cancer and the relationshipof the results of this questionnaire with clinical variables,laboratory data, quality of life, functional statusand comorbidity. MATERIAL AND METHODS: Patients over the ageof 75 with metastatic or castration-resistant prostatecancer were evaluated using the G8 questionnaire.Those with a G8 15 were subjected to comprehensivegeriatric assessment in order to evaluate the abilityof this questionnaire to predict frailty. We studiedthe relationship between G8 score and functionalstatus (ECOG), comorbidity (Charlson index), qualityof life (FACT-P and EQ5D 3L questionnaires), diseasecharacteristics and common analytical variables. RESULTS: 64 patients were included in the study,of whom 26 scored 15 in the G8 questionnaireand were referred to geriatrics. 89% (23/26) of thepatients with a G8 score pre-fragile and 7 fragile) and only 11% (3/26) wereconsidered robust. The multivariate model showsthat the Charlson index and the EQ5D 3L score areindependent predictors of frailty. The Charlson index(OR=1.68, p=0.022) increases the probability thatthe patient has a G8 score the EQ5D-3L score (OR-0.64, p-0.021) decreases thatprobability. Both quantitative variables were recodedinto binary variables from the most predictivepoint obtained from the ROC curves and included ina model: patients with Charlson index ≥4 (OR=3.17,p=0.047) and those with EQ5D- 3L score (OR=3.35, p=0.037) increased the likelihood of obtaininga G8 scoreconditions (neither Charlson ≥4 nor EQ5D-3L score 15. However, the presence of the two conditions increasesthe probability to 71.5%. CONCLUSIONS: The score obtained in the G8questionnaire is a good predictor of frailty in elderlypatients with advanced prostate cancer. Comorbidity,as measured by Charlson's index, and quality of life,as measured by the EQ5D-3L questionnaire, are independentpredictors of frailty (score on the G8 questionnairebelow 15).

OBJETIVO: Valorar la capacidad delcuestionario G8 para la detección de fragilidad enpacientes mayores de 75 años con cáncer de próstatametastásico o resistente a castración y la relación de losresultados de este cuestionario con variables clínicas,datos de laboratorio, calidad de vida, estado funcionaly comorbilidad.MATERIAL Y MÉTODOS: Se evaluó a pacientes ≥ 75años con cáncer de próstata metastásico o resistente acastración mediante el cuestionario G8. Aquellos conuna puntuación menor de 15 fueron sometidos a valoracióngeriátrica integral. Se evaluó la capacidad dedicho cuestionario para predecir fragilidad y se relacionaronlos hallazgos con el estado funcional (ECOG),comorbilidad (índice de Charlson), calidad de vida(cuestionarios FACT-P y EQ5D 3L), características de laenfermedad y variables analíticas habituales. RESULTADOS: Se incluyeron en el estudio 64 pacientes,de los cuales 26 obtuvieron una puntuación inferior a 15 en el cuestionario G8 y fueron remitidosal servicio de geriatría. El 89% (23/26) de los pacientescon una puntuación en el G8 por debajo de 15 presentabandatos de fragilidad (11 prefrágiles y 7 frágiles) ysolo el 11% (3/26) fueron considerados robustos. Elmodelo multivariado muestra, que de manera independiente,el índice de Charlson (OR=1,68, p=0,022)aumenta la probabilidad de que el paciente tenga unapuntuación en el cuestionario G8 por debajo de 15 y lapuntuación en el EQ5D-3L (OR=0,64, p=0,021) disminuyadicha probabilidad. Ambas variables cuantitativasse recodificaron en variables de tipo binario a partir delpunto más predictivo obtenido de las curvas ROC y seincluyeron en un modelo en el cual se objetivó, que pacientescon índice de Charlson ≥4 (OR= 3,17, p=0,047)y aquellos con puntuación en el cuestionario EQ5D-3Lde presentar una puntuación en el cuestionario G8Los pacientes que no presentan ninguna de estas condiciones(ni Charlson ≥4 ni EQ5D-3L score un 19% de probabilidad de presentar una puntuaciónen el cuestionario G8 condiciones aumenta la probabilidad hasta el 71,5%. CONCLUSIONES: La puntuación obtenida en elcuestionario G8 es un buen predictor de fragilidad enpacientes con cáncer de próstata avanzado con edad≥ 75 años. La comorbilidad, medida por el índice deCharlson, y la calidad de vida, medida por el cuestionarioEQ5D-3L, son predictores independientes de fragilidad,entendida como la obtención de una puntuaciónen el cuestionario G8 por debajo de 15.

Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group.

Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients.

Conventional white light imaging-assisted transurethral resection of bladder tumour (TURBT) versus IMAGE1S-assisted TURBT in non-muscle-invasive bladder cancer patients: trial protocol and 18 months results.

PURPOSE: White light (WL) is the traditional imaging modality for transurethral resection of bladder tumour (TURBT). IMAGE1S is a likely addition. We compare 18-mo recurrence rates following TURBT using IMAGE1S versus WL guidance. METHODS: Twelve international centers conducted a single-blinded randomized controlled trial. Patients with primary and recurrent non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by IMAGE1S or WL. Eighteen-month recurrence rates and subanalysis for primary/recurrent and risk groups were planned and compared by chi-square tests and survival analyses. RESULTS: 689 patients were randomized for WL-assisted (n = 354) or IMAGE1S-assisted (n = 335) TURBT. Of these, 64.7% had a primary tumor, 35.3% a recurrent tumor, and 4.8%, 69.2% and 26.0% a low-, intermediate-, and high-risk tumor, respectively. Overall, 60 and 65 patients, respectively, completed 18-mo follow-up, with recurrence rates of 31.0% and 25.4%, respectively (p = 0.199). In patients with primary, low-/intermediate-risk tumors, recurrence rates at 18-mo were significantly higher in the WL group compared with the IMAGE1S group (31.9% and 22.3%, respectively: p 0.035). Frequency and severity of adverse events were comparable in both treatment groups. Immediate and adjuvant intravesical instillation therapy did not differ between the groups. Potential limitations included lack of uniformity of surgical resection, central pathology review, and missing data. CONCLUSION: There was not difference in the overall recurrence rates between IMAGE1S and WL assistance 18-mo after TURBT in patients with NMIBC. However, IMAGE1S-assisted TURBT considerably reduced the likelihood of disease recurrence in primary, low/intermediate risk patients. REGISTRATION: ClinicalTrials.gov Identifier NCT02252549 (30-09-2014).

New frontiers in focal therapy for prostate cancer: Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging.

Imaging has a central role in the context of focal therapy (FT) for prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET. Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios. Limited evidence on PSMA PET/MRI is available in the setting of FT. PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa. PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence. The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography. PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT. Further studies are needed to confirm its applications in this specific clinical setting.

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines.

CONTEXT: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. EVIDENCE SYNTHESIS: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. CONCLUSIONS: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.

Genetic testing for the clinician in prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is one of the most common cancers worldwide and a leading cause of cancer-related mortality. Although the diagnosis and treatment of prostate cancer has improved substantially in recent years, new molecular biomarkers are needed to further prolong survival and improve the quality of life in these patients. AREAS COVERED: This review analyzes the current evidence for prognostic and predictive molecular biomarkers that can be applied across different clinical scenarios, ranging from localized disease to metastatic castration-resistant PCa, with a particular emphasis on the biomarkers likely to become available in routine clinical practice in the near future. EXPERT OPINION: There is a growing need for molecular testing to identify the most indolent types of prostate cancer to help optimize treatment strategies and spare treatment in these patients when possible. Current trends in the treatment of prostate cancer underscore the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting.

Invasive management of renal cell carcinoma in von Hippel-Lindau disease.

INTRODUCTION: Patients affected by von Hippel-Lindau (VHL) disease experience an increased risk for bilateral, synchronous, and metachronous renal cell carcinoma (RCC). Oncologic and functional outcomes are the main goals in the management of renal masses. We present our protocol for patients with VHL disease-associated RCC alongside functional and oncologic results observed in our series. MATERIAL AND METHODS: We performed a retrospective analysis of our clinical database of patients with VHL disease-associated RCC referred to our department between June 2005 and December 2017. We offer surveillance for lesions <2 cm and active management with radiofrequency ablation (RFA) for lesions 2-3 cm, and nephron-sparing surgery (NSS), RFA or embolization techniques for lesions >3 cm or growth rate >1 cm/year. RESULTS: Our series comprises 14 patients, of whom 13 had undergone at least one invasive procedure for RCC, mean age at first intervention was 27 years (range 18-60). Overall, 30 interventions were performed in 21 kidneys: four radical nephrectomies, 13 RFAs, 12 NSSs, and one embolization. During follow-up (median time: 41 months, range: 6-149), eight patients (57%) presented with new lesions that required treatment, with a mean time between treatments of 32 ±18.5 months. No metastatic progression or need for dialysis was recorded; the success rate for RFA was 85%. CONCLUSIONS: Management of VHL kidney disease by NSS is the standard of care with a cut-off at 3 cm, ablative procedures should be offered to lesions ranging 2-3 cm in size. Follow-up should be done strictly in referral centers that can provide all treatment options to renal function and control oncologic progression.

European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

CONTEXT: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies. OBJECTIVE: To provide updated practical recommendations for the diagnosis and management of PUC. EVIDENCE ACQUISITION: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed. EVIDENCE SYNTHESIS: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated. CONCLUSIONS: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC. PATIENT SUMMARY: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.

Clinical Applications of Molecular Biomarkers in Prostate Cancer.

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients. In this review, we evaluate current data on molecular biomarkers for PCa, with an emphasis on the biomarkers and gene panels with the most robust evidence to support their application in routine clinical practice.

Renal cell carcinoma and COVID-19 pandemia: Management strategies adapted to current practice. / Pandemia Covid-19 y cáncer renal: implicaciones y adaptación para un manejo óptimo de la enfermedad.

The COVID-19 pandemic caused by SARS-CoV-2 virus has caused an important health impact that has affected renal cell carcinoma management, among other urology areas. The high cancellation rate of surgeries, including those related to renal cancer, will cause an inevitable healthcare overload and probably a potential negative impact on its oncological outcomes, especially in locally advanced and metastatic renal cancer. Kidney cancer scenarios are quite different depending on their stage, distinguishing mainly between low priority of localized disease or high priority of locally advanced and metastatic under active treatment. The unknown pandemic duration and possibly fluctuating prevalence of the virus are likely to force an adaptation in the management of renal cell carcinoma among urology and oncology departments, ideally individualized ona case-by-case basis within multidisciplinary units. To this end, we present algorithms and tables regarding renal cell carcinoma management adapted to the COVID-19 period and stratified according to oncological stage, which might be useful for specialists dedicated to this uro-oncology area.

La pandemia COVID-19 causada por el virus SARS-CoV-2 ha provocado un importante impacto sanitario que ha afectado, entre otras áreas de la urología, al manejo del cáncer renal, tanto en su ámbito diagnóstico como de tratamiento. La elevada suspensión de intervenciones quirúrgicas, incluidas aquellas destinadas al tratamiento de esta patología, ocasionará una inevitable sobrecarga asistencial y quizá un potencial efecto deletéreo sobre sus resultados oncológicos, en especial en el cáncer renal localmente avanzado y en el metastásico. Los escenarios clínicos del carcinoma de células renales son bien distintos en función de su estadiaje, distinguiendo principalmente entre la baja prioridad de la enfermedad localizada o la alta prioridad del localmente avanzado y el metastásico en tratamiento activo. La duraciónin determinada y prevalencia posiblemente oscilante de la pandemia previsiblemente obligue a adaptar el manejo del cáncer renal en los servicios de urología y oncología, debiendo ser idealmente invidualizados según cada caso en el seno de unidades multidisciplinares. Para ello, se presentan algoritmos y tablas de manejo del cáncer renal adaptadas al periodo COVID-19 y estratificados según el estadio de la enfermedad, que puedan ser de utilidad para los especialistas dedicados a esta área de la uro-oncología.

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma.

BACKGROUND: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. OBJECTIVE: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. RESULTS AND LIMITATIONS: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. CONCLUSIONS: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. PATIENT SUMMARY: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

Salvage robot-assisted radical prostatectomy following failed local treatments.

Prostate cancer represents the most commonly diagnosed cancer in men and is the second-leading cause of cancer related death in the United States. Primary treatment for prostate cancer includes radiotherapy or ablative procedures such as cryotherapy, and high-intensity focused ultrasound (HIFU). Unfortunately, a large proportion of these patients, especially with high risk features, may experience disease recurrence within 10 years. Management of recurrent localized prostate cancer is heterogeneous, and radical surgery remains as a salvage option in these patients. The purpose of this article is to offer oncological arguments in favor of salvage robotic radical prostatectomy (sRARP), which could benefit a certain group of patients. Tips and tricks in order to perform a challenging salvage surgery are summarized, as evidence of modern series with acceptable morbidity rates.

ARTICULO SOLO EN INGLES. El cáncer de próstata es la neoplasia  más común diagnosticada en hombres y es el segundoen frecuencia en causa de muerte relacionada conel cáncer en los Estados Unidos. Aparte de la cirugía,el tratamiento primario para el cáncer de próstata incluyeradioterapia o procedimientos ablativos comola crioterapia, y ultrasonido focalizado de alta intensidad(HIFU). Sin embargo, una proporción de estospacientes, especialmente aquellos con criterios de altoriesgo, pueden experimentar recurrencia de la enfermedad.Como opción de tratamiento de rescate, existela posibilidad de ofrecer la prostatectomía radical aestos pacientes. El propósito de este artículo es ofrecerargumentos oncológicos a favor de la prostatectomíaradical robótica de rescate, lo que podría beneficiara un determinado grupo de pacientes. Se resumen lasseries más relevantes con abordaje mínimamente invasivopublicadas hasta la fecha demostrando tasas demorbilidad aceptables.

High sensitivity detection of extracellular vesicles immune-captured from urine by conventional flow cytometry.

Extracellular vesicles (EVs) provide an invaluable tool to analyse physiological processes because they transport, in biological fluids, biomolecules secreted from diverse tissues of an individual. EV biomarker detection requires highly sensitive techniques able to identify individual molecules. However, the lack of widespread, affordable methodologies for high-throughput EV analyses means that studies on biomarkers have not been done in large patient cohorts. To develop tools for EV analysis in biological samples, we evaluated here the critical parameters to optimise an assay based on immunocapture of EVs followed by flow cytometry. We describe a straightforward method for EV detection using general EV markers like the tetraspanins CD9, CD63 and CD81, that allowed highly sensitive detection of urinary EVs without prior enrichment. In proof-of-concept experiments, an epithelial marker enriched in carcinoma cells, EpCAM, was identified in EVs from cell lines and directly in urine samples. However, whereas EVs isolated from 5-10 ml of urine were required for western blot detection of EpCAM, only 500 µl of urine were sufficient to visualise EpCAM expression by flow cytometry. This method has the potential to allow any laboratory with access to conventional flow cytometry to identify surface markers on EVs, even non-abundant proteins, using minimally processed biological samples.

Impact of Metabolic Diseases, Drugs, and Dietary Factors on Prostate Cancer Risk, Recurrence, and Survival: A Systematic Review by the European Association of Urology Section of Oncological Urology.

CONTEXT: To date, established risk factors for prostate cancer (PCa) are limited to age, race, family history, and certain genetic polymorphisms. Despite great research efforts, available evidence on potentially modifiable risk factors is conflicting. Moreover, most studies on PCa risk factors did not consider the impact of prostate-specific antigen (PSA) testing on PCa diagnosis. OBJECTIVE: To provide a detailed overview of the latest evidence on the role of metabolic diseases, drugs, and dietary factors for risk of PCa incidence, recurrence, and survival in men exposed to PSA testing. EVIDENCE ACQUISITION: A systematic review of the English-language literature was performed using the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Randomized, case-control, or cohort studies published during the periods 2008-2017 (on drugs and metabolic diseases) and 2003-2017 (on dietary factors), with extensive follow-up (≥8-10yr for studies on PCa risk; ≥2-5yr for studies on PCa recurrence, progression, and survival, depending on the review subtopic) and adjusting of the analyses, beyond established risk factors, for either rate of PSA testing (for risk analyses) or PCa stage and primary treatment (for survival analyses), were eligible for inclusion. EVIDENCE SYNTHESIS: Overall, 39 reports from 22 observational studies were included. Studies were heterogeneous regarding definitions of exposure or outcomes, length of follow-up, risk of bias, and confounding. For some risk factors, evidence was insufficient to assess potential effects, while for others there was no evidence of an effect. For selected risk factors, namely metformin, aspirin and statin use, diabetes, obesity, and specific dietary intakes, there was low-quality evidence of modest effects on PCa risk. CONCLUSIONS: Current evidence from long-term observational studies evaluating the effect of drugs, metabolic diseases, and dietary factors for PCa risk considering the impact of PSA testing is still not conclusive. Future research is needed to confirm the associations suggested by our review, exploring their potential biological explanations and selecting those risk factors most likely to trigger effective public health interventions. PATIENT SUMMARY: We reviewed the available studies published in the recent literature on the potential role of drugs, metabolic diseases, and food and dietary factors for the risk of prostate cancer, considering the impact of prostate-specific antigen testing on prostate cancer diagnosis. We found that for some factors data are currently insufficient to make definitive conclusions, while for others available studies seem to indicate an effect on the risk of prostate cancer.

Salvage robotic-assisted radical prostatectomy: oncologic and functional outcomes from two high-volume institutions.

INTRODUCTION: While no consensus on the optimal salvage treatment exists, only 3% of these patients will get salvage radical prostatectomies due to the assumed technical challenges of this procedure. OBJECTIVES: Our goal is to analyze the perioperative, oncologic and functional outcomes of patients undergoing salvage robotic-assisted radical prostatectomy (sRARP) after primary treatment failure. MATERIALS AND METHODS: Data were prospectively collected and retrospectively reviewed from a combined database of more than 14,800 patients who had undergone RARP. We identified 96 patients who underwent sRARP after RT or ablative techniques. Primary cancer characteristics, surgical data, pathology results, perioperative complications, oncologic and functional outcomes were analyzed. RESULTS: Sixty-eight patients (70.8%) received some source of RT as a primary treatment. The remaining 28 patients: 18 (18.75%) received cryotherapy, seven (7.92%) HIFU, one electroporation, one microwave and one Tookad. complication was seen in 25 (26%) patients (21 minor and 4 major complications). Anastomotic leak was the most common complication, found in 14 (14.6%) of the cases. No rectal injuries occurred. Fourteen (15%) patients had a biochemical failure after a median follow-up of 14 (IQR 5-24) months. Fifty-five (57.3%) of them self-reported to be pad-free at 12 months. Seventeen (55%) of 31 pre-operative potent patients (SHIM score > 21), were potent with or without the use of PDE5i at 12 months. CONCLUSIONS: sRARP is a feasible alternative for PCa recurrence. Technically the procedure is challenging and should be performed by experienced PCa surgeons. Major complications are uncommon. Continence and potency recovery is possible, but at lower rates than for non-salvage patients.

Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and Progression: A Systematic Review of the Literature by the European Association of Urology Section of Oncological Urology (ESOU).

CONTEXT: Smoking, sexual activity, and physical activity (PA) are discussed as modifiable lifestyle factors associated with prostate cancer (PCa) development and progression. OBJECTIVE: To evaluate the available evidence concerning the association of smoking, sexual activity, and sports and exercise on PCa risk, treatment outcome, progression, and cancer-specific mortality. EVIDENCE ACQUISITION: A systematic review of studies published between 2007 and 2017 using MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement criteria was conducted. EVIDENCE SYNTHESIS: While data concerning the impact of smoking on PCa development remain conflicting, there is robust evidence that smoking is associated with aggressive tumor features and worse cancer-related outcome, which seems to be maintained for 10 yr after smoking cessation. Less convincing and limited evidence exists for the association of sexual activity with PCa risk. The findings related to PA and PCa support the inference that exercise might be a useful factor in the prevention of PCa and tumor progression, while it is not finally proved under which specific conditions PA might be protective against disease development. CONCLUSIONS: Smoking is associated with aggressive tumor features and worse cancer-related prognosis; as this negative impact seems to be maintained for 10yr after smoking cessation, urologists should advise men to quit smoking latest at PCa diagnosis to improve their prognosis. As several studies indicate a positive impact of exercise on tumor development, progression, and treatment outcome, it is certainly reasonable to advocate an active lifestyle. Least convincing evidence is available for the interaction of sexual activity and PCa, and well-conducted and longitudinal studies are clearly necessary to evaluate whether the suggested associations between PCa risk and sexual behavior are real or spurious. PATIENT SUMMARY: In this systematic review, we looked at the impact of smoking, sexual activity, and sports and exercise on prostate cancer risk and outcome after treatment. While the evidence for sexual activity is not overall clear, we found that smoking might lead to more aggressive cancers and result in worse treatment outcome. Physical activity might prevent prostate cancer and improve cancer-related outcomes as well. Hence, it is certainly reasonable to advocate an active lifestyle and advise men to quit smoking.