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Posterior rhabdosphincter reconstruction (PRR) has been proposed to improve early urinary continence (UC) recovery after radical prostatectomy (RP). In order to generate level 1b evidence, we designed a double-blind randomised controlled trial powered to detect a 20% increase in early UC recovery after robot-assisted RP (RARP). A group of 153 patients with cT1c–3a N0M0 prostate cancer were randomised (73 to control arm and 80 to PRR arm) and 152 completed 12-mo follow-up. For UC defined as no pad use, the recovery hazard ratio at 1-mo follow-up was 2.312 (95% confidence interval [CI] 1.081–4.937; p = 0.030). UC recovery was observed in 33.8% of patients in the PRR arm and 18.1% of patients in the control arm (p = 0.022). At 3-mo follow-up the corresponding rates were 58.8% and 43.1% (p = 0.038). The median time to UC recovery was 106 d (95% CI 73–139) in the control arm and 64 d (95% CI 39–89) in PRR arm (p = 0.897). No differences in pathological outcomes or early and late surgical complications were observed between the arms. We conclude that PRR is safe and increases early UC recovery after RARP. Patient summary We investigated reconstruction of a muscular ring that controls the flow of urine, called the rhabdosphincter, after removal of the prostate in robot-assisted surgery. The procedure is safe and increases early recovery of urinary continence. This trial is registered at ClinicalTrials.gov as NCT03302169.

Background: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation “Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer” was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available. Objective: To assess current ADT use before prostate cancer surgery in Europe. Design, setting, and participants: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres. Outcome measurements and statistical analysis: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence. Results and limitations: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0–32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0–43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated. Conclusions: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued. Patient summary: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it.

Poly (ADP-ribose) polymerase (PARP) inhibitors have antitumor activity in advanced prostate cancer associated with loss of homologous recombination repair (HRR) function. About 20% of all patients with advanced prostate cancer present germline or tumor mutations in HRR-related genes, the most common being BRCA2, mutated in approximately 10% of all advanced prostate cancers. Challenges related to sample availability, tumor heterogeneity and access to NGS technology need to be addressed for a successful implementation of genomic stratification in routine clinical practice. The recent regulatory approvals of PARP inhibitors olaparib and rucaparib represent the first molecular biomarker-guided drugs for men with prostate cancer. While these findings represent a significant advance in the field of precision medicine and prostate cancer, there are still many unsolved questions on the optimal use of PARP inhibitors in this disease. Several clinical trials have shown that different mutations in various genes are associated with distinct magnitudes of sensitivity to PARP inhibitors, with BRCA2 mutations associating with more frequent and durable responses, questioning the benefit for subset of patients with mutations in other HRR-associated genes. In this review, we scrutinize the clinical development of different PARP inhibitors for the treatment of advanced prostate cancer, and we discuss how the study of additional biomarkers and the design of rational drug combinations can maximize patient benefit from this drug class.

Resumen Introduccion Se recomienda realizar una biopsia prostatica (PBx) de repeticion ante una sospecha persistente de cancer de prostata (PCa) o cuando se identifica proliferacion acinar atipica (ASAP), neoplasia intraepitelial de alto grado (HGPIN) extensa (≥ 3 zonas de biopsia) o HGPIN con celulas atipicas sospechosas de adenocarcinoma (PIN-ATYP). Actualmente se recomienda realizar una resonancia magnetica multiparametrica (mpMRI) y PBx guiada por mpMRI (MRI-TBx) en una PBx de repeticion. Nuestro objetivo fue analizar el valor actual para predecir el riesgo de PCa clinicamente significativo (csPCa) del hallazgo de ASAP, mHGPIN, PIN-ATYP y otros hallazgos histologicos. Metodos Se realizo un analisis retrospectivo de 377 PBx de repeticion. Se realizo MRI-TBx cuando la puntuacion PI-RADS fue ≥ 3 y PBX sistematicas de 12 cilindros guiadas por ecografia transrectal (TRUS) cuando fue ≤ 2. ASAP, HGPIN, HGPIN multifocal (mHGPIN), PIN-ATYP y otros 8 hallazgos histologicos fueron reportados prospectivamente en las PBx negativas. El csPCa fue definido como grado ISUP ≥ 2. Resultados La incidencia de ASAP, mHGPIN y PIN-ATYP fue 4,2%, 39,7% y 3,7% respectivamente, y la tasa de csPCa fue estadisticamente similar en los pacientes con estos hallazgos histologicos. Sin embargo, las tasas de csPCa con atrofia proliferativa inflamatoria (PIA) presente y ausente fueron 22,2% y 36,1%, respectivamente. La PIA fue el unico hallazgo histologico que predijo un menor riesgo de csPCa, con OR de 0,54 (IC 95%: 0,308-0,945, p = 0,031). La PIA fue, tambien, un factor predictor independiente en un modelo combinando variables clinicas y mpMRI, que obtuvo un area bajo la curva de 0,86 (95% IC: 0,83-0,90). Conclusiones La PIA resulto ser el unico hallazgo histologico predictor del riesgo de csPCa, y puede contribuir en un modelo predictivo; mHGPIN no fue predictor de riesgo de csPCa. La baja incidencia de ASAP (4,2%) y PIN-ATYP (3,7%) impidio que pudieramos obtener conclusiones sobre estas lesiones.

Cathepsin D; Magnetic resonance imaging; Proclarix Catepsina D; Imatges per ressonància magnètica; Proclarix Catepsina D; Imágenes por resonancia magnética; Proclarix Proclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm3), respectively. Among 100 men with negative mpMRI (PI-RADS

Resumen Contexto y objetivo La incontinencia urinaria es el efecto secundario con mayor impacto en la calidad de vida despues de la prostatectomia radical. El objetivo de nuestro articulo es revisar la evidencia cientifica actual sobre las variaciones quirurgicas descritas para preservar la continencia urinaria despues de la prostatectomia radical. Adquisicion de la evidencia Se realizo una revision sistematica de la literatura en PubMed, Cochrane y ScienceDirect segun los criterios PRISMA (Preferred reporting items for systematic reviews and meta-analyses), utilizando los terminos: urinary continence, urinary incontinence, urinary leakage, radical prostatectomy, open radical prostatectomy, laparoscopic prostatectomy, robot assisted laparoscopic prostatectomy, robotic prostatectomy y los criterios de seleccion PICO. Se identificaron 1.603 referencias de las que se seleccionaron 27 publicaciones que cumplieron los criterios de inclusion, 6 fueron ensayos clinicos aleatorizados y 4 metaanalisis. Sintesis de la evidencia Las tecnicas mas empleadas para alcanzar una continencia urinaria precoz son la preservacion del cuello vesical, de las bandeletas neurovasculares y la reconstruccion del rabdoesfinter, siendo esta la tecnica con mayor evidencia, ya que existen 3 ensayos clinicos aleatorizados. Pese que algunas variaciones tecnicas han conseguido mejorias en los resultados funcionales, la ausencia de consenso en la definicion de incontinencia urinaria y la manera de evaluarla no permiten elaborar recomendaciones tecnicas basadas en evidencia cientifica de calidad. Conclusiones La reconstruccion del rabdoesfinter es la unica tecnica que ha demostrado mejoria en la recuperacion precoz de la continencia urinaria tras la prostatectomia radical. La evidencia cientifica actual es heterogenea y limitada, por lo que son necesarios estudios aleatorizados bien disenados para evaluar las modificaciones tecnicas.

Background and objective Urinary incontinence is the adverse effect with more impact on patients’ quality of life after undergoing radical prostatectomy. The objective of this study is to review the present evidence that describes the variations on surgical techniques which aim to preserve urinary continence after radical prostatectomy. Evidence acquisition We searched the literature on PubMed, Cochrane, and ScienceDirect according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement, using the PICO review protocol. The search terms were urinary continence, urinary incontinence, urinary leakage, radical prostatectomy, open radical prostatectomy, laparoscopic prostatectomy, robot-assisted laparoscopic prostatectomy, robotic prostatectomy. We identified 1603 registers, and 27 articles were reviewed for meeting the inclusion criteria. Six of them are randomized clinical trials and 4 of them, meta-analysis. Evidence synthesis The surgical techniques more frequently used to achieve early urinary continence are bladder neck and neurovascular bundles preservation, as well as the reconstruction of the rhabdosphincter. The latter has been presented in three randomized clinical trials. Even though some approaches have obtained improved functional outcomes, the lack of consensus on the definition of urinary incontinence and its measurement methods have not advocated for the creation of technical recommendations based on scientific evidence. Conclusions The reconstruction of the rhabdosphincter is the only technique that has shown improved functional results through randomized trials. The current evidence is limited and heterogenous, and more studies with consistent criteria are needed in order to establish a standard surgical technique.

Resumen Objetivos Evaluar la eficacia y la eficiencia de la biopsia prostatica sistematica (BPS) y la biopsia de prostata por fusion cognitiva (BPFC) para diagnosticar el cancer de prostata (CaP) y el CaP significativo (CaPs) y analizar si la BPFC podria reemplazar con seguridad a la BPS. Material y metodos Una cohorte de 314 hombres consecutivos que tenian PI-RADS ≥ 2 en una biopsia previa 3T resonancia magnetica multiparametrica se sometieron prospectivamente a BPFC ecografica transrectal (dos nucleos por area sospechosa hasta un maximo de tres areas) y una BPS de 12 nucleos perifericos. Se considero CaPs cuando el grado de la OMS fue superior a 2 (Gleason 4 + 3 o superior). Resultados Se diagnostico CaP en 133 pacientes (42,4%), de los que 83 (62,4%) fueron CaPs. La BPS detecto CaP en 114 hombres (85,7%) y BPFC en 103 (77,4%), p Conclusiones Las BPFC son mas efectivas y tambien mas eficientes que las BPS para detectar CaPs. Sin embargo, las BPFC aun no pueden reemplazar las BPS de manera segura porque no pueden detectar hasta el 15% de los CaPs.

Prostate cancer (PC) suspicion is based on prostate-specific antigen (PSA) and digital rectal examination (DRE). Multiparametric magnetic resonance imaging (mpMRI) increases prostate biopsy (PBx) specificity and sensitivity for detection of aggressive PC.To identify who benefits from mpMRI according to biopsy scenario (initial biopsy [IBx] vs repeated biopsy [RBx]) and the risk of aggressive PC according to PSA-DRE groups (G1, PSA10ng/ml and -DRE; G2, PSA10ng/ml and +DRE; G3, PSA ≥10ng/ml and -DRE; G4, PSA ≥10ng/ml and +DRE).We carried out a retrospective analysis for 768 consecutive men with PC suspicion and scheduled for PBx in a referral institution in 2016 and 2017.Pelvic 3-T mpMRI scanning, targeted biopsy (TBx) for suspicious lesions (Prostate Imaging-Reporting and Data System [PI-RADS] score1), and 12-core systematic biopsy (SBx).We measured the rate of PBx procedures that could be avoided and the rate of high-grade PC (HGPC) that would be missed among men with negative mpMRI, and the increase in HGPC detection due to TBx. Univariate and multivariate analyses were performed.The rate of avoidable biopsies (PI-RADS3) was 24.2% overall, with 25.7% for IBx and 20.5% for RBx (p=0.057). The IBx and RBx rates were 31.2% and 19.8% in G1, 13.5% and 30.4% in G2, 23.7% and 21.9% in G3, and 2.5% and 0% in G4, respectively. The overall rate of missed HGPC was 1.0% for IBx and 6.5% for RBx (p=0.170), while the IBx and RBx rates were 1.1% and 5.2% for G1, 2.0% and 11.1% for G2, 0% and 7.7% for G3, and 0% and 0% for G4, respectively (p0.001). The rate of HGPC (PI-RADS 3-5) diagnosed following TBx increased to 23.9% for IBx and to 32.6% for RBx overall (p0.001), while the IBx and RBx rates were 29.0% and 45.5% for G1, 20.0% and 33.3% for G2, 40.0% and 38.9% for G3, and 0% and 0% for G4, respectively (p0.001). Limitations are the single-institution design, the lack of randomisation, and small samples for subgroup analyses.mpMRI was of no benefit for men with PSA ≥10ng/ml and +DRE. Among the other men, mpMRI was of benefit in IBx and RBx as would reduce the biopsy rate by up to 25.7% and increase the net HGPC detection rate by up to 28.4%.All men with suspected prostate cancer could benefit from multiparametric prostate cancer and targeted biopsy except for those with prostate-specific antigen ≥10ng/ml and positive digital rectal examination. The benefits include avoiding unnecessary prostate biopsy procedures and increasing the detection of aggressive cancer.

The efficacy of tools for selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (MRI) varies across Prostate Imaging-Reporting and Data System (PI-RADS) categories. The new Proclarix test performs better than prostate-specific antigen density and the European Randomized Study of Screening for Prostate Cancer MRI predictive model in the challenging PI-RADS 3 category. Proclarix guaranteed 100% detection of clinically significant prostate cancer (PCa), avoiding almost one-quarter of prostate biopsies and decreasing overdetection of insignificant PCa from 16.6% to 11.2%. Prostate Imaging-Reporting and Data System (PI-RADS) category 3 is a challenging scenario for detection of clinically significant prostate cancer (csPCa) and some tools can improve the selection of appropriate candidates for prostate biopsy. To assess the performance of the European Randomized Study of Screening for Prostate Cancer (ERSPC) magnetic resonance imaging (MRI) model, the new Proclarix test, and prostate-specific antigen density (PSAD) in selecting candidates for prostate biopsy among men in the PI-RADS 3 category. We conducted a head-to-head prospective analysis of 567 men suspected of having PCa for whom guided and systematic biopsies were scheduled between January 2018 and March 2020 in a single academic institution. A PI-RADS v.2 category 3 lesion was identified in 169 men (29.8%). csPCa, insignificant PCa (iPCa), and unnecessary biopsy rates were analysed. csPCa was defined as grade group ≥2. Receiver operating characteristic (ROC) curves, decision curve analysis curves, and clinical utility curves were plotted. PCa was detected in 53/169 men (31.4%) with a PI-RADS 3 lesion, identified as csPCa in 25 (14.8%) and iPCa in 28 (16.6%). The area under the ROC curve for csPCa detection was 0.703 (95% confidence interval [CI] 0.621-0.768) for Proclarix, 0.657 (95% CI 0.547-0.766) for the ERSPC MRI model, and 0.612 (95% CI 0.497-0.727) for PSAD (p = 0.027). The threshold with the highest sensitivity was 10% for Proclarix, 1.5% for the ERSPC MRI model, and 0.07 ng/ml/cm 3 for PSAD, which yielded sensitivity of 100%, 91%, and 84%, respectively. Some 21.3%, 26.2%, and 7.1% of biopsies would be avoided with Proclarix, PSAD, and the ERSPC MRI model, respectively. Proclarix showed a net benefit over PSAD and the ERSPC MRI model. Both Proclarix and PSAD reduced iPCa overdetection from 16.6% to 11.3%, while the ERSPC MRI model reduced iPCa overdetection to 15.4%. Proclarix was more accurate in selecting appropriate candidates for prostate biopsy among men in the PI-RADS 3 category when compared to PSAD and the ERSPC MRI model. Proclarix detected 100% of csPCa cases and would reduce prostate biopsies by 21.3% and iPCa overdetection by 5.3%. We compared three methods and found that the Proclarix test can optimise the detection of clinically significant prostate cancer in men with a score of 3 on the Prostate Imaging-Reporting and Data System for magnetic resonance imaging scans

Background: Lymph node (LN) status is a key prognostic factor in the decision-making process of prostate cancer (PCa) management. Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies.Methods: To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria.Results: Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques.Conclusion: OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence encourages its usage in PCa patients to improve LN staging and prognosis.

INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-making process for prostate cancer (PC) management. Sectioning and haematoxylin-eosin (HE) staining tech...

Resumen Introduccion Las biopsias prostaticas (BP) de repeticion, ante la persistencia de la sospecha de cancer de prostata (CP), son frecuentes y su rendimiento bajo. En el contexto de una BP negativa existe un escenario microscopico (EM), que definimos como el conjunto de lesiones no neoplasicas identificable. La existencia de algunas de estas lesiones incrementa el riesgo de deteccion de CP en BP sucesivas, mientras que otras parecen tener un efecto protector. El objetivo de esta revision sistematica es identificar el conjunto de lesiones que puede formar parte del EM de una BP negativa y analizar la evidencia actual de su asociacion con el riesgo de deteccion de CP en BP sucesivas. Adquisicion de la evidencia Dos revisores independientes realizaron una busqueda bibliografica en Medline, Embase y Central Cochrane, con los terminos de busqueda: small acinar proliferation or ASAP or prostatic intraepithelial neoplasia or HGPIN or adjacent small atypical glands or pinatyp or atrophy or proliferative inflammatory atrophy or pia or prostatic inflammation or prostatitis and prostate cancer. Se identificaron 1.015 referencias y siguiendo los principios de la declaracion PRISMA y de seleccion PICO, se identificaron 57 articulos originales validos para esta revision. Sintesis de la evidencia La proliferacion acinar atipica de celula pequena se asocia a una tasa de deteccion de CP en BP sucesivas que oscila entre el 32 y 48%. La neoplasia intraepitelial prostatica de alto grado (HGPIN) se asocia a CP entre el 13 y 42%, siendo su multifocalidad la que define el incremento en el riesgo de deteccion. La atrofia prostatica, la atrofia proliferativa inflamatoria y la infamacion prostatica parecen tener un efecto protector sobre la deteccion de CP en BP sucesivas. Por otra parte, el riesgo de deteccion de CP en varones con HGPIN multifocal se reduce significativamente si coexiste atrofia proliferativa inflamatoria. Conclusiones El EM de una BP negativa puede estar compuesto por las lesiones de proliferacion acinar atipica de celula pequena, HGPIN, atrofia prostatica, atrofia proliferativa inflamatoria e infamacion prostatica ya que todas parecen estar asociadas al riesgo de deteccion de CP en BP sucesivas. Esta revision nos permite generar la hipotesis de que el EM de una BP negativa puede ser de utilidad en la decision indicar BP de repeticion.

Introduction In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyze the current evidence of their association with the risk of detecting PC in subsequent PBs. Evidence acquisition Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. Evidence synthesis Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13–42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. Conclusions The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB.

Resumen Introduccion y objetivos La incontinencia urinaria es una de las principales complicaciones tras la prostatectomia radical. El objetivo del estudio fue describir las caracteristicas anatomicas, evaluadas preoperatoriamente mediante resonancia magnetica, que permitan predecir la recuperacion precoz de la continencia urinaria tras la prostatectomia radical asistida por robot. Material y metodos Se analizo prospectivamente a 72 pacientes tratados mediante prostatectomia radical asistida por robot. Los resultados funcionales se evaluaron mediante los cuestionarios EPIC (1, 6 y 12 meses) y la fecha de primera continencia autoinformada. La longitud de la uretra membranosa (LUM) y el angulo entre la LUM y el eje prostatico (aLUMP) fueron evaluados preoperatoriamente en imagenes sagitales ponderadas en T2. Resultados La tasa de continencia fue del 67,2, el 92,6 y el 95,2% a 1, 6 y 12 meses, respectivamente. Los pacientes con valores de aLUMP inferiores alcanzaron continencia urinaria temprana: al mes, los continentes habian tenido una aLUMP media de 107,21° (IC del 95% 90,3-124,6), mientras que entre los que presentaban incontinencia era de 118,5° (IC del 95% 117,7-134); p = 0,014. Hemos encontrado diferencias en el aLUMP entre los grupos segun la continencia a los 6 meses: angulo en continentes de 114,24° (IC del 95% 104,6-123,9), mientras que en los incontinentes habia sido 142° (IC del 95% 126,5-157,6), p = 0,015. A los 12 meses, los continentes tenian una LUM preoperatoria significativamente superior a los incontinentes. En el analisis multivariante solamente el aLUMP fue un predictor independiente de continencia urinaria a los 6 meses OR 0,007 (IC del 95% 0,002-0,012), p = 0,012. Conclusiones La evaluacion de parametros anatomicos preoperatorios previos a la cirugia puede ayudar a definir que pacientes recuperaran la continencia urinaria precozmente, auxiliando a la toma de decisiones terapeuticas.

Resumen Contexto y objetivo En los ultimos anos se han producido avances significativos en el conocimiento de la carcinogenesis renal. Hoy en dia los tumores renales se clasifican en funcion de su perfil genetico, y ademas se han desarrollado tratamientos especificos basados en la identificacion de dianas terapeuticas. Sin embargo, todavia no se han identificado marcadores pronosticos. El objetivo de esta revision es analizar la literatura que ha evaluado la expresion de la proteina STAT3 como marcador molecular en el carcinoma renal de celula clara (ccRCC). Adquisicion de evidencia En enero de 2018 se realizo una busqueda sistematica de la literatura en Pubmed, Cochrane Library y Sciencedirect de las publicaciones realizadas desde 1990. Los terminos de busqueda fueron renal cell carcinoma and STAT3 or STAT-3 and prognostic factor. Se siguieron los principios de la declaracion PRISMA y la estrategia de seleccion PICO, seleccionandose los articulos originales con series de pacientes diagnosticados de ccRCC localizado o metastasico, donde se analiza la actividad de STAT3 como marcador pronostico. Se identificaron 132 publicaciones de las que finalmente se han revisado 10 por cumplir los criterios de inclusion. Sintesis de evidencia La activacion (fosforilacion) de STAT3 (pSTAT3) en el residuo Ser727 es importante en el desarrollo y progresion de ccRCC. La expresion de pSTAT3 parece ser un marcador pronostico y predictor de resistencia a algunos tratamientos en pacientes con enfermedad diseminada. Existe poca evidencia de su utilidad como un marcador pronostico en pacientes con enfermedad localizada. Conclusiones La expresion de pSTAT3(Ser727) en el nucleo de las celulas del ccRCC puede ser un marcador pronostico y de respuesta al tratamiento en pacientes con ccRCC. La evidencia cientifica actual es limitada y son necesarios mas estudios que demuestren su utilidad.

Context and objective There have been significant advances in the knowledge of renal carcinogenesis in the last years. Nowadays, renal tumours are classified according to their genetic profile and specific treatments based on the identification of therapeutic targets have also been developed. However, no prognostic markers have yet been identified. The aim of this review is to analyze literature that has evaluated the expression of the STAT3 protein as a molecular marker in clear cell renal carcinoma (ccRCC). Evidence acquisition In January 2018 a systematic review was conducted in Pubmed, Cochrane library and Sciencedirect databases, from papers published from 1990. Search terms were “renal cell carcinoma” and “STAT3” or “STAT-3” and prognostic factor. Following the principles of the PRISMA declaration and the PICO selection strategy, original articles with series of patients diagnosed with localized or metastatic ccRCC, and where the activity of STAT3 is analyzed as a prognostic marker, were selected. A total of 132 publications were identified, of which 10 were finally revised, for they met the inclusion criteria. Evidence synthesis STAT3 activation (phosphorylation) through Ser727 is important during ccRCC development and progression. PSTAT3 expression seems to be a prognostic marker and an antiangiogenic-resistance marker in metastatic patients. There is little evidence as prognostic marker in patients with localized disease. Conclusions STAT3 (Ser 727) expression in the nucleus of the ccRCC cells can be a prognostic marker and an antiangiogenic-resistance marker. Current scientific evidence is limited and more studies are needed to demonstrate its usefulness.

Diagnosis; Proclarix; Prostate cancer Diagnóstico; Proclarix; Cáncer de próstata Diagnòstic; Proclarix; Càncer de pròstata Purpose To analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE). Materials and Methods Proclarix score (0%–100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs. Results The area under the curve of Proclarix was 0.701 (95% CI 0.637–0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701–0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed. Conclusions Proclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection.

TPS209 Background: Multiple lines of evidence suggest a crosstalk between androgen receptor (AR) signaling and DNA damage repair (DDR) in prostate cancer. Co-targeting both pathways in mHNPC can result in a clinically relevant synergistic effect. ZZFIRST trial is evaluating the combination of TALA –a poly(ADP-ribose) polymerase inhibitor– and EZ –an AR signaling inhibitor– in mHNPC patients. Methods: This is a multicenter, open-label, randomized, investigator-initiated phase 2 clinical trial. Men aged ≥18 years with histologically confirmed mHNPC, an ECOG performance status of 0-1, and a prostate-specific antigen (PSA) ≥4 ng/mL at enrolment are eligible. Patients must have not received previous systemic treatment for locally advanced or mHNPC. A total of 54 patients will start treatment with EZ 160 mg/day for 2 28-day cycles in addition to standard androgen-deprivation therapy (ADT). Patients are then randomized and stratified based on homologous recombination gene alterations on a 1:2 ratio to either continue EZ 160 mg/day, or to receive EZ 160 mg/day plus TALA 0.5 mg/day. In both arms, patients will continue ADT throughout the trial. Treatment will continue until progressive disease (PD) or unacceptable toxicity. PSA will be determined every 4 weeks and radiological tumor extend will be assessed at screening and every 8 weeks for the 6 initial months of treatment and every 12 weeks thereafter until PD. Primary endpoint is PSA-complete response defined as the percentage of patients with PSA < 0.2 ng/mL at 12 months of therapy. Secondary endpoints include PSA-complete response at any time point and at month 7, PSA response ( < 4 ng/ml) at 7 and 12 months, PSA-progression-free survival (PSA-PFS), radiologic PFS, time to castration resistance based on PSA-PFS and rPFS, and overall survival. Safety will be assessed as per NCI-CTCAE 5.0. Exploratory endpoints include analysis of transcriptional changes in AR and DDR pathways and assessment of genomic signatures on tumor and liquid biopsies collected at baseline, 4 weeks, and PD. An imaging sub-study of whole-body diffusion weighted MRI will help to further study antitumor activity and drug resistance mechanisms. This trial was opened to accrual in July 2020. Currently 44 patients have been enrolled (with 37 randomized by cycle 3 day 1) out of 54 expected. Analysis will be assessed with the exact binomial test. At least 11 patients must maintain PSA < 0.2 ng/mL by 12 months of therapy among 32 evaluable patients in the combination arm to justify further investigation of this strategy. A drop-out rate of 10% has been considered. Clinical trial information: NCT04332744.

Background Repeat prostate biopsy (PBx) is recommended under persistent suspicion of prostate cancer (PCa) or in the face of the following findings: atypical small acinar proliferation (ASAP); extense (≥3 biopsy sites) high-grade prostatic intraepithelial neoplasia (HGPIN); or HGPIN with atypical glands; suspicious for adenocarcinoma (PIN-ATYP). Nowadays; multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted PBx (MRI-TBx) are recommended in repeat PBx. Our objective was to analyze the current value of ASAP; mHGPIN; PIN-ATYP and other histological findings to predict clinically significant PCa (csPCa) risk. Methods Retrospective analysis of 377 repeat PBxs. MRI-TBx was performed when Prostate Imaging-Reporting and Data System (PI-RADS) score >3 and 12-core transrectal ultrasound (TRUS) systematic PBx when ≤2. ASAP; HGPIN; mHGPIN; PIN-ATYP; and 8 other histological findings were prospectively reported in negative PBx. CsPCa was defined as ISUP group grade >2. Results Incidence of ASAP; multifocal HGPIN (mHGPIN) and PINATYP was 4.2%; 39.7% and 3.7% respectively; and csPCa rate was statistically similar among men with these histological findings. However; the rate of csPCa was 22.2% when proliferative inflammatory atrophy (PIA) was present; and 36.1% when it was not. PIA was the only histological finding which predicted lower risk of csPCa; with an OR of 0.54 (95%CI: 0.308−0.945; P = .031). In addition; PIA was an independent predictor of a model combining clinical variables and mpMRI which reached area under de ROC curve of 0.86 (95%CI: 0.83−0.90). Conclusion PIA emerged as the only predictive histological finding of csPCa risk and can contribute to a predictive model. mHGPIN failed to predict csPCa risk. The low incidence of ASAP (4.2%) and PIN-ATYP (3.7%) prevented us from drawing conclusions.