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Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas. (C) 2019 Elsevier Inc. All rights reserved.

BACKGROUND A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Objectives To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. Patients and methods We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. Results In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. Conclusion Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS.

Context The oncological efficacy of routine lymphadenectomy (lymph node dissection [LND]) at the time of radical nephroureterectomy (RNU) remains controversial. Objective To systematically review the available literature assessing the impact of LND in upper tract urothelial carcinoma (UTUC) patients. Evidence acquisition Embase, Medline, and Cochrane databases were searched for all studies comparing outcomes of patients undergoing RNU without LND versus any form of LND. We identified nine retrospective studies eligible for inclusion in this systematic review. We took cancer-specific survival (CSS) as the primary end point, and performed a narrative review and risk of bias assessment. Evidence synthesis Six studies compared outcomes of no LND versus LND. Three studies compared complete LND versus incomplete LND versus no LND. The incidence of pN+ in patients with high-stage (≥pT2) tumours ranged from 14.3% to 40%. Pre- and postoperative characteristics differed among the study groups, potentially biasing the results, as demonstrated by the risk of bias assessment, potentially favouring the LND group. Oncological outcomes such as cancer-specific, overall, recurrence-free, and metastasis-free survival were reviewed, demonstrating a survival benefit with LND in high-stage disease of the renal pelvis. Conclusions Template-based and complete LND improves CSS in patients with high-stage (≥pT2) UTUC and reduces the risk of local recurrence. The impact of LND in ureteral tumours remains uncertain. Patient summary Studies comparing radical nephroureterectomy with or without the removal of nodes (lymph node dissection [LND]) were analysed. LND improves survival in patients with high-stage disease of the renal pelvis, if it is performed according to an anatomical template-based approach.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non–muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004–2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from 40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non–muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. The updated European Association of Urology prognostic factor risk groups for patients with non–muscle-invasive bladder cancer provide urologists with information that they should take into account when choosing a patient's treatment and scheduling follow-up.

The authors regret that a co-author was mistakenly missed from the authorship. The following co-author should have been included in the authorship: Peter-Paul M. Willemse Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands

Objectives To analyze the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methods A descriptive retrospective study of RP was conducted at our center from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. Results A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25–75 37.92–135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% C I 86.7–92.9%), 73.3% (95% CI 68–78.6%) and 51.4% (95% CI 43.8–59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4–97.2%), 84.0% (95% CI 79.3–88.7%) and 75.5% (95% CI 68.8–82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1–90.7%), 72.2% (95% CI 66.7–77.7%) and 61.7% (95% CI 54.3–69.1%), respectively. A total of 120 patients of 477 analyzed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. Conclusions RP plus extended lymphadenectomy should be the first therapeutic maneuver when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Resumen Objetivos Analizar los resultados oncologicos mas relevantes en el tratamiento mediante prostatectomia radical (PR) en el cancer de prostata de alto riesgo (CPAR) en un hospital oncologico. Material y metodos Estudio retrospectivo descriptivo de las PR realizadas en nuestro centro desde 1986 a 2017 en CPAR para conocer como objetivo primario las supervivencia global (SG) y cancer especifica (SCE), y como objetivos secundarios las supervivencias libre de progresion bioquimica (SLPB), libre de progresion metastatica (SLPM), la necesidad de tratamiento de rescate (SLTR), la necesidad de hormonoterapia (SLHT) y finalmente el desarrollo de cancer de prostata resistente a la castracion. Se realizan analisis de regresion de Cox para establecer modelos predictivos y conocer el peso de cada variable definitoria de alto riesgo. Resultados Se realizaron 2.093 PR de las cuales 480 (22,9%) fueron en CPAR. La mediana de seguimiento de la serie global fue 79,57 meses (P25-75 37,92-135,16). No se realizo linfadenectomia (LDN) en el 6,5% de los casos, mientras que fue LDN obturatriz en 51,2% y extensa en 42,3%. La SG a 5, 10 y 15 anos fue de 89,8% (IC 95%: 86,7-92,9%), 73,3% (IC 95%: 68-78,6%) y 51,4% (IC 95%: 43,8-59%). La SCE a 5, 10 y 15 anos fue de 94,8% (IC 95%: 92,4-97,2%), 84,0% (IC 95%: 79,3-88,7%) y 75,5% (IC 95%: 68,8-82,2%) La SLPM a 5, 10 y 15 anos fue de 87,4% (IC 95%: 84,1-90,7%), 72,2% (IC 95%: 66,7-77,7%) y 61,7% (IC 95%: 54,3-69,1%) respectivamente. Se requirio radioterapia de rescate en 120 pacientes de 477 analizados (25,1%) y 293/477 nunca han requerido hormonoterapia (61,4%). En relacion con el uso de HT en los 93 pacientes pN1, 33 (35,5%) no la han necesitado. El tiempo desde la PR a la progresion bioquimica es la variable de mayor peso pronostico para la SLPM, la SCE y la SG. Conclusiones La PR mas LDN extensa deberia ser la primera maniobra terapeutica cuando es factible dentro de una estrategia multimodal. Es necesario un seguimiento mayor de la serie para validar la hipotesis de unos mejores resultados oncologicos basandose en una aplicacion mas precoz de la RT de rescate, una LDN extensa y los farmacos prolongadores de supervivencia en la fase de CPRC.

Item does not contain fulltext PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

An early single instillation of intravesical chemotherapy (SICI) used immediately after transurethral resection of the bladder (TURB) can significantly reduce the recurrence rate in selected patients with non-muscle-invasive bladder cancer (NMIBC). SICI should be used in patients with low-risk and with selected intermediate-risk tumours, in particular for multiple primary small papillary tumours, single primary papillary tumours >3cm, and single recurrent papillary tumours recurring >1yr after the previous resection. The available data do not support any recommendation to reduce the role of SICI in patients after fluorescence cystoscopy-guided TURB or en bloc TURB. SICI can even provide some benefit in patients with intermediate-risk tumours subsequently treated with further instillations. During instillation, contraindications should be taken into account and safety measures should be applied. PATIENT SUMMARY: An early single instillation of intravesical chemotherapy immediately after transurethral resection of the bladder can significantly reduce the recurrence rate in selected patients with non-muscle-invasive bladder cancer. It should be used in patients with low-risk and selected intermediate-risk tumours.

To evaluate the efficacy of the Advance® and AdvanceXP® slings in men with stress urinary incontinence (SUI) post-radical prostatectomy and to identify predictive factors for outcome. Included were male patients with SUI following radical prostatectomy who had a positive “repositioning test”, 24 h-pad weight (PW) test

Resumen Objetivos Determinar el comportamiento del PCA3 como un marcador de segunda linea en un programa de cribado oportunista de cancer de prostata (CaP) y su comparacion con la calculadora de riesgo 3 del cribado aleatorizado europeo en cancer de prostata (ERSPC RC-3). Material y metodos Un total de 5.199 hombres de 40-75 anos se hicieron la prueba del antigeno prostatico especifico (PSA) y un tacto rectal (TR). Aquellos con TR normal y PSA ≥ 3 ng/ml se realizaron un PCA3. Todos los hombres con PCA3 ≥ 35 se hicieron biopsia inicial (BxI) —12 cilindros—. Aquellos con PCA3 Resultados PCA3 se testo en 838 hombres (16,1%). En los grupos PCA3(+) y PCA3(–), las tasas de deteccion global de CaP fueron del 40,9 y del 14,7% a una mediana de seguimiento de 21,7 meses (p Conclusiones Cuando se usa PCA3-35 como biomarcador de segunda linea en hombres con PSA ≥ 3 ng/ml y TR normal, se puede obviar la BxI un 12,5% menos que usando la ERSPC RC-3, pero reduciendo los falsos negativos un 36,2%. A un seguimiento de 21,7 meses, este protocolo dual no hubiera detectado un 9,1% de CaP clinicamente significativo, por lo que el seguimiento con estrictos criterios de biopsia basados en PSA y TR es obligatorio en casos con PCA3

Context There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Objective To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. Evidence acquisition A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Evidence synthesis Seven studies compared KSS overall ( n =547) versus RNU ( n =1376). Information on the comparison of SU ( n =586) versus RNU ( n =3692), URS ( n =162) versus RNU ( n =367), and PC ( n =66) versus RNU ( n =114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Conclusions Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. Patient summary We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.

BackgroundAlthough guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.ObjectiveTo bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DesignA steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SettingOnline Delphi survey and consensus conference.ParticipantsThe European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysisStatements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), and 7–9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).Results and limitationsOverall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.ConclusionsThese consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.Patient summaryThis report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Aims Artificial urinary sphincter (AUS) AMS-800® is an effective treatment for male stress urinary incontinence. The aim of the study was to assess the long-term effectiveness and complications of artificial urinary sphincter placement preserving the bulbospongiosus muscle. Methods From April 2004 to March 2014, all consecutive male patients with urinary incontinence who underwent an AUS prosthesis insertion were prospectively evaluated. Surgical technique consisted of a perineal incision for cuff placement around the bulbous urethra preserving the bulbospongiosus muscle. Cure rate was defined as no pad use. Results A total of 82 consecutive patients (median age 68 years, range: 54-78) were prospectively evaluated (median follow-up 46 months, range: 12-135). Bulbospongiosus muscles were preserved intact in all cases with no intraoperative complications. Postoperative complications were reported in 14 patients (1 urethral erosion). The overall cure rate (dry rate) was 76.8% and the median ICIQ-UI score improved from 18 (range: 8-21) to 4 (range: 0-17) (P

To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital.A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk.A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (PRP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Objectives: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). Material and methods: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA >= 3 ng/ml had a PCA3 test done. All men with PCA3 >= 35 underwent an initial biopsy (IBx) 12 cores. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. We compared them to those obtained with ERSPC RC-3. Results: PCA3 test was performed on 838 men (16.1%). In PCA3(+) and PCA3(-) groups, global PCa detection rates were 40.9% and 14.7% with a median follow-up (FU) of 21.7 months (P= 3 ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protocol would miss 9.1% of clinically significant PCa, so strict FU is mandatory with established biopsy criteria based on PSA and DRE in cases with PCA3 < 35. (C) 2016 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.

Resumen Objetivos Conocer la informacion necesaria para reproducir los resultados de la literatura en vigilancia activa (VA) en cancer de prostata (CaP) en nuestro propio centro, de tal forma que dicha informacion sea objetiva y se le pueda dar al paciente de forma fehaciente. Contemplamos estudiar el porcentaje de pacientes candidatos a VA y que la escogen en nuestro ambiente, los datos de infraestadificacion, infragradacion y prediccion de CaP insignificante, depurar el poder predictivo de distintas variables clinicas para mejorar nuestros criterios de seleccion y analizar los resultados de nuestros pacientes en VA. Material y metodos Revision retro y prospectiva de nuestras bases de datos. Se analiza un periodo de un ano natural seleccionando posibles candidatos a VA. Analisis de nuestras prostatectomias radicales para conocer las tasas de infraestadificacion, infragradacion y tasa de CaP insignificante (criterios de Epstein). Analisis uni/multivariado de variables clinicas en pacientes con tumor insignificante en pieza de prostatectomia radical. Valoracion prospectiva de supervivencia global y libre de tratamiento activo (SLTA) en pacientes en VA. Resultados Entre octubre de 2010 y octubre de 2011, un 44,7% de los CaP cumplian criterios para ser incluidos en VA, y un 11,2% la escogieron. Nuestros porcentajes de infraestadificacion, infragradacion y tasa de CaP insignificante fueron 14%; 31,4%; y 55,7% respectivamente, pero solo 6 pacientes (6,97%) tuvieron CaP ≥ pT3a + Gleason ≥ 7 + volumen > 0,5 cc. En el estudio multivariado para prediccion de tumor insignificante, la densidad de PSA y el numero de cilindros afectos son factores independientes. Con un seguimiento medio de 36 ± 39 meses, de 232 incluidos en VA, 63 pacientes pasaron a tratamiento activo (27,1%), solo 13 por ansiedad sin progresion patologica. La mediana del tiempo de SLTA es de 72,7 meses (IC 95%: 30,9-114,4). La SLTA a los 24 meses es del 76,4% (69,7-83,1%) y a 48 meses es del 58,1% (48,8-67,4%). Solo 10 pacientes (4,3%) fallecieron, 9 por causa diferente al CaP. La supervivencia global estimada a 5 anos es del 92,8% (IC 95%: 86,7-98,9%). Conclusiones El conocimiento exacto de la casuistica de cada centro deberia ser obligatorio para informar a los pacientes verazmente de la rentabilidad de la biopsia y de si los porcentajes de infragradacion, infraestadificacion y de CaP insignificante se adecuan a los de la literatura. A 3 anos reproducimos los resultados de las series mas longevas de VA, por lo que el programa de VA puede seguir implementandose e incluyendo cada vez a mas pacientes.

Aims Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor recently described to be mutated in prostate cancer (PCa). Hence, studying the gene expression profile and the presence of SPOP mutations in PCa and understanding its clinico-pathological significance as prognostic and therapeutic biomarker are important to further understand its role in PCa development. Patients and methods A cohort of 265 paraffin-embedded PCa samples from patients with more than 5years of follow-up and treated with radical prostatectomy were collected at our institution for SPOP evaluation. RT-qPCR analysis was performed for expression studies while mutations were assessed by next generation sequencing. Relationship with prognosis was analysed using log-rank analysis and multivariable Cox regression. Results SPOP was found to be strongly down-regulated in PCa (median=0.24; range=0.04–9.98) and its expression was associated with both, biochemical ( p =0.003) and clinical progression free survival ( p =0.023), the very low SPOP expression levels being associated to the worst prognosis. Multivariate analysis demonstrated that low levels of SPOP independently predicted a worse prognosis for both, biochemical (Hazard ratio (HR)=0.5; confidence interval (CI) 95% [0.4–0.9], p =0.011) and clinical progression (HR=0.6; IC 95% [0.4–1], p =0.046). SPOP mutations were found in 10% of TMPRSS2-ERG (T2E)-negative cases. Log-rank tests showed that mutations were significantly associated with biochemical progression free survival (BPFS) ( p =0.009) and also were significant in the multivariable analysis (HR=3.4; IC 95% [1.5–7.6], p =0.004). Conclusions The present study demonstrates that prognosis varies depending on SPOP expression and mutational status, hence, defining a new biotype of PCa associated with a worse prognosis.

Objectives To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. Materials and methods A retro- and prospective review of our databases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. Results Between October-2010 and October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% chose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had ≥pT3a + Gleason ≥7 + volume >0.5 cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36 ± 39 months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9–114.4). SFAT at 24 months was 76.4% (69.7–83.1%) and at 48 months 58.1% (48.8–67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7–98.9%). Conclusions It should be mandatory to have the exact knowledge of the local data of each center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

Objectives To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. Material and methods We performed a prospective evaluation of PCA3 as a second-line biomarker in an opportunistic screening for prostate cancer (PCa). From September 2010 until September 2012, 2,366 men, aged 40–74 years and with >10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA > 3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) —12cores—. Men with PCA3 .5 ng/ml at 4-6months or PSAv > .75 ng/ml/year. Results With a median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (p Conclusions PCA3 as a second-line biomarker within an opportunistic dual screening protocol can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa.

Resumen Objetivos Reducir el numero de biopsias (Bx) innecesarias en un programa de cribado oportunista en cancer de prostata (CaP). Material y metodos Estudio prospectivo y aleatorizado evaluando el PCA3 como biomarcador de segunda linea. De septiembre de 2010 a septiembre de 2012 2.366 hombres con edad en rango 40-74 anos, y mas de 10 anos de expectativa de vida, fueron estudiados mediante PSA y tacto rectal (TR), excluyendo los biopsiados previamente o con infeccion urinaria reciente. Ante un TR sospechoso y/o PSA > 3 ng/ml se les realizo un PCA3. A todos aquellos con PCA3 ≥ 35 se les realizo una Bx inicial (IBx) —12 cilindros—. Con PCA3 0,5 ng/ml a 6 meses o PSAv > 0,75 ng/ml/ano. Resultados Con un seguimiento medio de 10,1 meses se testo el PCA3 en 321/2.366 hombres (13,57%), 289 en la primera visita y 32 durante el seguimiento. Entre los 110 hombres con PCA3+ (34,3%) se identifico CaP en 43 en IBx (39,1%). En el brazo aleatorizado 110 se observaron y 101 se biopsiaron, encontrando 12 CaP (11,9%), mostrando un reduccion en la deteccion de CaP estadisticamente significativa en esta cohorte (p Conclusiones El PCA3 como biomarcador de segunda linea en un programa de cribado oportunista podria potencialmente evitar un 65,7% de IBx y 50,1% a 10 meses de seguimiento, dejando de diagnosticar 3,2% de CaP de alto grado.

Objectives To implement the use of nomograms in clinical practice showing how to choose thresholds in nomograms’ predictions to select risk groups. To validate and compare the predictive ability and clinical utility of the Hospital Universitario ‘Miguel Servet’ (HUMS) and the updated Partin Tables 2012 (PT-2012) nomograms to predict organ-confined disease (OCD) after radical prostatectomy (RP). Patients and Methods Cohort of 1285 patients with prostate cancer treated with RP at Instituto Valenciano de Oncologia (IVO) between 1986 and 2011. The predictive value of the nomograms was assessed by means of calibration curves, discrimination ability (area under the receiver operating characteristic (ROC) curve (AUC) and probability density functions). The clinical utility was evaluated through Vickers’ decision curves and thresholds were chosen through probability density functions. Results The calibration curves showed a minimal underestimation in low probabilities ( 50%) in the HUMS nomogram and a regular minimal overestimation in the PT-2012. Their AUC of 0.7285 (95% confidence interval [CI] 0.7010–0.7559) and 0.7288 (95%CI 0.7013–0.7562) respectively, show an adequate discrimination ability for both predictive models in the IVO cohort. The decision curves show similar net benefits for both models. In this study we advocate for a threshold of 53% for the identification of OCD. Conclusions The HUMS-nomogram and the PT-2012 predictions of OCD confirm their utility in a contemporary cohort of patients. Patients with a probability of OCD >53% should be classified as OCD, helping physicians to better counsel their patients. A selection of adequate thresholds, as presented in this paper, makes nomograms more accessible tools.

Bladder cancer is the most common malignancy of the urinary tract. About 75%-85% of patients present with non-muscle-invasive bladder cancer (NMIBC). However, patients with pT1 tumors, as well as all those with high-grade disease, make up a subset with a high-risk of recurrence and disease progression. Although still regarded as the gold standard, clinical evidence from contemporary published series clearly demonstrates that transurethral resection of tumor (TUR) is a procedure far from optimal, highlighting its limitations and the need for further diagnostic accuracy. Routine use of a restaging TUR (re-TUR), supported by the American Urological Association and European Association of Urology guidelines, detects residual tumor in a significant number of cases after initial TUR. It provides a more accurate staging of the disease and, consequently, helps to guide its treatment. Recent years have seen rapid development of novel optical techniques aimed to optimize resection. Routine implementation of these novel techniques in the context of re-TUR is promising and may potentially result in more tumors being identified and completely resected, leading to significantly lower residual tumor rates than with the standard white-light TUR. This article will focus on re-TUR in the management of high-risk NMIBC, with an up-to-date review of the available literature and detailed analysis of the published series.

Background: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Methods: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference’s nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. Results: We detect 28 % of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20 % at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95 %:0.68–0.79) and 0.786 for HGPCa (C.I.95 %:0.71–0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40 % could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31 % for the threshold probability of 40 %. Conclusions: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40 % should be counseled to undergo an IBx if opportunistic screening is required.

To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS.A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS.Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%).It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

Purpose: miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis. Materials and Methods: Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip (R) miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluated for these miRNAs. Results: miR-182 and 187, the miRNAs most differentially expressed between normal and tumor tissue, were selected for further validation. miR-187 inversely correlated with cT (p = 0.125) and pT (p = 0.0002) stages, Gleason score (p = 0.003) and TMPRSS2-ERG status (p = 0.003). The log rank test showed associations of miR-182 with biochemical (p = 0.026) and clinical (p = 0.043) progression-free survival, as also noted on multivariate analysis. A significant independent improvement in the definition of risk of progression was achieved by combining miR-182 expression with Gleason score (p < 0.0001). miR-187 detection in urine provided an independent predictive value for positive biopsy. A prediction model including serum prostate specific antigen, urine PCA3 and miR-187 provided 88.6% sensitivity and 50% specificity (AUC 0.711, p = 0.001). Conclusions: Results show that miR-182 and 187 are promising biomarkers for prostate cancer prognosis to identify patients at risk for progression and for diagnosis to improve the predictive capability of existing biomarkers.

To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer.We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12cores-. Men with PCA335 were randomized 1:1 to either IBx or observation. Re-biopsy(16-18 cores) criteria were PSA increase.5 ng/ml at 4-6 months or PSAv.75 ng/ml/year.With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P.001). Area under the curve for PSA and PCA3 were .601 and .74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment.PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa.