Xpert Bladder Cancer Monitor for the Early Detection of Non-Muscle Invasive Bladder Cancer Recurrences: Could Cystoscopy Be Substituted?

XBM was prospectively assessed in spontaneous urine collected just before flexible cystoscopy and washing cytology carried out within the first 2 years follow-up of 337 patients with NMIBC. Recurrences were pathologically confirmed in 49 patients (14.5%), 22 of them being high-risk (6.5%). The XBM sensitivity for detecting any type of recurrence was 69.4% and 63.6% in the cases of high-risk NMIBC. Negative predictive value (NPV) for XBM was 93% for all recurrences and 96.2% for high-risk recurrences. XBM could have avoided 213 invasive controls but missed the detection of 15 recurrences (30.6%)-8 of them of high-risk (36.4%). XBM false positive elevations were detected in 90 patients (26.7%), whereas 10 patients with the invasive method had a false positive result (3%), p <0.001. However, early detection of recurrences during the first year's follow-up after an XBM false positive result was observed in 18 patients (20%). On the other hand, 19 recurrences were detected during this period among the rest of the patients (7.7%)-p = 0.003, and odds ratio (OR) 3.0 (95% CI 1.5-6.0). Regarding one-year follow-up recurrences, 10% were high-risk recurrences in the XBM false positive group and 3.2% in the rest of the patients-p = 0.021, and OR 3.3 (95% CI 1.2-8.9). Additionally, 11.3% of the patients without false positive results developed a recurrence, p = 0.897, for any recurrence, being 10% and 5.2%, respectively, and high-risk and low-risk recurrences, p = 0.506. After searching for the best XBM cutoff for detecting the 38 high-risk initial recurrences and the early high-risk recurrences after a one-year follow-up, a linear discriminant analysis (LDA) of 0.13 could have avoided 11.3% of cystoscopies and bladder wash cytologies, as this cutoff missed only 1 high-risk recurrence (2.6%). More extensive and well-designed studies will confirm if XBM can improve the surveillance of NMIBC.

[Optimization biomarkers in the surveillance of non muscle invasive bladder cancer.] / Optimización del seguimiento de tumores vesicales no músculo invasivo con biomarcadores.

INTRODUCTION: Bladder cancer is thefifth most common tumor in the world. Moreover, it isone of the most expensive due to its high recurrencerate. Urinary biomarkers for surveillance of non muscleinvasive bladder cancer is a promising and growingfield due to the invasiveness of the actual methods, basedon cystoscopy and cytology. Although current EuropeanGuidelines only consider the use of biomarkersin the low risk scenario as an alternative to cystoscopywhen the patient declines invasive methods for the follow-up after surgery, there is increasing evidence oftheir safety in high risk tumors. MATERIAL AND METHODS: We have performeda review of the main urinary biomarkers, includingFDA-approved ones, protein-based and genetic biomarkers.We have also described the different options to incorporatethe biomarkers in the clinical practice. RESULTS: There are not randomized control trialscomparing any biomarker with the gold standard follow-up. Most of the papers published so far are cohortstudies, limitating the evidence of the results. Biomarkerscan be used as an alternative of cystoscopy, in a noninvasive follow-up, or alternating both tests. There arefew economical studies comparing both options, but theevidence supports the efficiency of the main biomarkers. CONCLUSIONS: Cystoscopy and cytology are the goldstandard for non muscle invasive bladder cancer surveillance.2021 European Guidelines suggest, for the firsttime, an alternative use of biomarkers in a concrete lowgrade scenario to avoid invasive explorations to patientswith low risk of progression. Paradoxically, biomarkers(mainly genetic ones) have a very good profile of sensitivityand negative predictive value in the high risk scenario.Although there is increasing evidence to supporttheir implementation, the lack of fase IV trials hinderstheir daily use.

INTRODUCCIÓN: El carcinoma vesicales el quinto tumor más frecuente en el mundo. Dehecho, es uno de los que más recursos económicosconsume debido a su alta tasa de recurrencia. Los biomarcadoresurinarios para el seguimiento del tumorvesical no músculo invasivo es un campo prometedory en pleno crecimiento debido a la invasividad de losactuales métodos de seguimiento, basados en la cistoscopiay la citología de orina. A pesar de que las actualesGuías Europeas sólo consideran el uso de biomarcadoresen el escenario del tumor vesical de bajoriesgo como alternativa a la cistoscopia cuando el pacienteno desee procedimientos invasivos para el seguimientotras la cirugía, existe creciente evidencia desu seguridad en los tumores de alto riesgo.MATERIAL Y MÉTODOS: Se ha realizado una revisiónnarrativa de los principales biomarcadores urinarios,incluyendo los aprobados por la FDA, los basados enproteínas y los marcadores genéticos. Se han descritoigualmente las diferentes opciones para la incorporaciónde los biomarcadores en la práctica clínica diaria.RESULTADOS: No existen ensayos clínicos randomizadosque comparen los biomarcadores urinariosfrente al gold estándar en el seguimiento. La mayoría delos artículos hasta la fecha son estudios de cohortes, limitandola evidencia de los resultados. Los biomarcadores pueden ser utilizados como alternativa a la cistoscopia,en un seguimiento no invasivo, o alternandoambas pruebas. Existen pocos estudios económicosque comparen ambas opciones, pero la evidencia parecesoportar la eficiencia de los principales biomarcadores.CONCLUSIONES: La cistoscopia y la citología son elgold estándar para el seguimiento del tumor vesicalno músculo infiltrante. Las Guías Europeas de 2021sugieren, por primera vez, el uso alternativo de losbiomarcadores urinarios en el escenario concreto delbajo grado con el fin de evitar exploraciones invasivasa pacientes con muy bajo riesgo de progresión. Paradójicamente,los biomarcadores (principalmente losgenéticos) presentan un mejor perfil de sensibilidad yvalor predictivo negativo en el escenario del alto riesgo.A pesar de que existe creciente evidencia para recomendarsu implementación, la ausencia de ensayosclínicos fase IV dificulta su aplicación en la práctica diaria.

Optimización del seguimiento de tumores vesicales no músculo-invasivos con biomarcadores / Optimization biomarkers in the surveillance of non muscle invasive bladder cáncer

INTRODUCCIÓN: El carcinoma vesical es el quinto tumor más frecuente en el mundo. Dehecho, es uno de los que más recursos económicosconsume debido a su alta tasa de recurrencia. Los biomarcadores urinarios para el seguimiento del tumorvesical no músculo invasivo es un campo prometedory en pleno crecimiento debido a la invasividad de losactuales métodos de seguimiento, basados en la cistoscopia y la citología de orina. A pesar de que las actuales Guías Europeas sólo consideran el uso de biomarcadores en el escenario del tumor vesical de bajoriesgo como alternativa a la cistoscopia cuando el paciente no desee procedimientos invasivos para el seguimiento tras la cirugía, existe creciente evidencia desu seguridad en los tumores de alto riesgo.MATERIAL Y MÉTODOS: Se ha realizado una revisiónnarrativa de los principales biomarcadores urinarios,incluyendo los aprobados por la FDA, los basados enproteínas y los marcadores genéticos. Se han descritoigualmente las diferentes opciones para la incorporación de los biomarcadores en la práctica clínica diaria.RESULTADOS: No existen ensayos clínicos randomizados que comparen los biomarcadores urinariosfrente al gold estándar en el seguimiento. La mayoría delos artículos hasta la fecha son estudios de cohortes, limitando la evidencia de los resultados. Los biomarcadores pueden ser utilizados como alternativa a la cistoscopia, en un seguimiento no invasivo, o alternandoambas pruebas. Existen pocos estudios económicosque comparen ambas opciones, pero la evidencia parece soportar la eficiencia de los principales biomarcadores.CONCLUSIONES: La cistoscopia y la citología son elgold estándar para el seguimiento del tumor vesicalno músculo infiltrante. Las Guías Europeas de 2021sugieren, por primera vez, el uso alternativo de losbiomarcadores urinarios en el escenario concreto de

INTRODUCTION: Bladder cancer is thefifth most common tumor in the world. Moreover, it isone of the most expensive due to its high recurrencerate. Urinary biomarkers for surveillance of non muscle invasive bladder cancer is a promising and growingfield due to the invasiveness of the actual methods, based on cystoscopy and cytology. Although current European Guidelines only consider the use of biomarkersin the low risk scenario as an alternative to cystoscopywhen the patient declines invasive methods for the follow-up after surgery, there is increasing evidence oftheir safety in high risk tumors. MATERIAL AND METHODS: We have performeda review of the main urinary biomarkers, includingFDA-approved ones, protein-based and genetic biomarkers. We have also described the different options to incorporate the biomarkers in the clinical practice.RESULTS: There are not randomized control trialscomparing any biomarker with the gold standard follow-up. Most of the papers published so far are cohortstudies, limitating the evidence of the results. Biomarkers can be used as an alternative of cystoscopy, in a noninvasive follow-up, or alternating both tests. There arefew economical studies comparing both options, but theevidence supports the efficiency of the main biomarkers.CONCLUSIONS: Cystoscopy and cytology are the goldstandard for non muscle invasive bladder cancer surveillance. 2021 European Guidelines suggest, for the firsttime, an alternative use of biomarkers in a concrete lowgrade scenario to avoid invasive explorations to patientswith low risk of progression. Paradoxically, biomarkers(mainly genetic ones) have a very good profile of sensitivity and negative predictive value in the high risk scenario. Although there is increasing evidence to supporttheir implementation, the lack of fase IV trials hinderstheir daily use.

Perioperative and Functional Outcomes of Robot-assisted Ureteroenteric Reimplantation: A Multicenter Study of Seven Referral Institutions.

BACKGROUND: Open revision of ureteroenteric strictures (UESs) is associated with considerable morbidity. There is a lack of data evaluating the feasibility of robotic revisions. OBJECTIVE: To analyze the perioperative and functional outcomes of robot-assisted ureteroenteric reimplantation (RUER) for the management of UESs after radical cystectomy (RC). DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study of 61 patients, who underwent 63 RUERs at seven high-volume institutions between 2009 and 2020 for benign UESs after RC, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Variables associated with being stricture free after an RUER were evaluated using a multivariate Cox regression analysis. RESULTS AND LIMITATIONS: Among 63 RUERs, 22 were right sided (35%), 34 left sided (54%), and seven bilateral (11%). Twenty-seven (44%) had prior abdominal/pelvic surgery and five (8%) radiotherapy (RT). Thirty-two patients had American Society of Anesthesiologists (ASA) scores I-II (52%) and 29 ASA III (48%). Forty-two (68%) RUERs were in ileal conduits, 18 (29%) in neobladders, and two (3%) in Indiana pouch. The median time to diagnosis of a UES from cystectomy was 5 (3-11) mo. Of the UESs, 28 (44%) failed an endourological attempt (balloon dilatation/endoureterotomy). The median RUER operative time was 195 (175-269) min. No intraoperative complications or conversions to open approach were reported. Twenty-three (37%) patients had postoperative complications (20 [32%] were minor and three [5%] major). The median length of hospital stay was 3 (1-6) d and readmissions were 5%. After a median follow-up of 19 (8-43) mo, 84% of cases were stricture free. Lack of prior RT was the only variable associated with better stricture-free survival after RUER (hazard ratio 6.8, 95% confidence interval 1.10-42.00, p = 0.037). The study limitations include its retrospective nature and the small number of patients. CONCLUSIONS: RUER is a feasible procedure for the management of UESs. Prospective and larger studies are warranted to prove the safety and efficacy of this technique. PATIENT SUMMARY: In this study, we investigate the feasibility of a novel minimally invasive technique for the management of ureteroenteric strictures. We conclude that robotic reimplantation is a feasible and effective procedure.

The future of bladder cancer therapy: Optimizing the inhibition of the fibroblast growth factor receptor.

Therapeutic options for metastatic bladder cancer (BC) have seen minimal evolution over the past 30 years, with platinum-based chemotherapy remaining the mainstay of standard of care for metastatic BC. Recently, five immune checkpoint inhibitors (ICIs) have been approved by the FDA as second-line therapy, and two ICIs are approved as first-line treatment in selected patients. Molecular alterations of muscle-invasive bladder cancer (MIBC) have been reported by The Cancer Genome Atlas. About 15% of patients with MIBC have molecular alterations in the fibroblast growth factor (FGF) axis. Several ongoing trials are testing novel FGF receptor (FGFR) inhibitors in patients with FGFR genomic aberrations. Recently, erdafitinib, a pan-FGFR inhibitor, was approved by the FDA in patients with metastatic BC who have progressed on platinum-based chemotherapy. We reviewed the literature over the last decade and provide a summary of current knowledge of FGF signaling, and the prognosis associated with FGFR mutations in BC. We cover the role of FGFR inhibition with non-selective and selective tyrosine kinase inhibitors as well as novel agents in metastatic BC. Efficacy and safety data including insights from mechanism-based toxicity are reported for selected populations of metastatic BC with FGFR aberrations. Current strategies to managing resistance to anti-FGFR agents is addressed, and the importance of developing reliable biomarkers as the therapeutic landscape moves towards an individualized therapeutic approach.

Comparison of standard vs. palliative management for bladder cancer in patients older than 85 years: multicenter study of 317 de novo tumors.

BACKGROUND: The peak incidence of bladder cancer (BCa) occurs at 85 years but data on treatment and outcome are sparse in this age group. We aimed to compare the outcomes of high-grade nonmuscle invasive BCa (HG NMIBC) and muscle invasive BCa (MIBC) treated with standard therapies vs. palliative management in patients >85 years. METHODS: Retrospective multicenter study of 317 patients >85 years who underwent transurethral resection (TURB) for de novo BCa between 2014 and 2016. Standard management consisted in following EAU-guidelines and palliative in monitoring patients without applying oncological treatments after TURB. Low-grade tumors were not compared because all of them were considered to have followed a standard management. RESULTS: Median age was 87 years (85-97). ASA-score was as follows: II, 34.7%; III, 52.1%; IV, 13.2%. Pathological examination showed: 86 Low-grade NMIBC (27.1%), 156 HG NMIBC (49.2%), and 75 MIBC (23.7%). Median follow-up of the series was 21 months (3-61) and median overall survival (OS) 29 (24-33). Among HG NMIBC, 77 patients (49.4%) received standard treatments (BCG, restaging TURB) and 79 (50.6%) palliative management. Among MIBC, 24 (32%) received standard management (cystectomy, radiotherapy, chemotherapy) and 51 (68%) palliative. Applying standard management in HG NMIBC was an independent prognostic factor of OS (44 months vs. 24, HR 1.95; P = 0.013) and decreased the emergency visit rate (33% vs. 43%). In MIBC, the type of management was not a related to OS (P = 0.439) and did not decrease the emergency visit rate (33% vs. 33%). ASA and Charlson-score were not predictors of OS in HG NMIBC (P = 0.368, P = 0.386) and MIBC (P = 0.511, P = 0.665). CONCLUSIONS: Chronological age should not be a contraindication for applying standard therapies in NMIBC. In MIBC the survival is low regardless of the type of management. The lack of correlation between OS and ASA or Charlson-score raises the necessity of a geriatric assessment for selecting the best treatment strategy.

A Robot-Assisted Complete Urinary Tract Extirpation in a Patient with Simultaneous Panurothelial Carcinoma: A Case Report.

Background: Despite concomitant bladder and upper urinary tract cancers are present in 17% of cases, the simultaneous affection of the urethra, bladder, and both upper urinary tracts is extremely rare. Treatment decisions in this setting could be challenging because of the lack of evidence in the literature. Case Presentation: A 65-year-old Caucasian man with a history of nine low-grade (LG) and multifocal bladder tumor recurrences during the past 4 years is referred to our department with a newly diagnosed panurothelial carcinoma involving the bladder, urethra, and both upper urinary tracts. Because of the large and recurrent LG bladder tumor, the urethral involvement and the presence of bilateral pyelocaliceal tumors >4 cm the patient underwent a robot-assisted complete urinary tract extirpation (CUTE). Operating time was 360 minutes and blood loss 460 mL. No intraoperative complications were reported and blood transfusion was not required. The patient developed a surgical site infection in the glans that was solved with antibiotics without any other postoperative complication. He started renal replacement therapy and was discharged 6 days after the surgery. Pathologic analysis showed multifocal urothelial carcinomas; pTa LG involving the bladder and the prostatic-bulbar-membranous-penile urethra, pT3 high grade (HG) in right renal pelvis, pT1 HG in left renal pelvis, and pN0 in pelvic lymph node dissection. After a reasonable free-recurrence period of time the patient could be evaluated for a robot-assisted intracorporeal urinary diversion in preparation for a later renal transplantation. Conclusion: Robot-assisted CUTE could be a feasible and safe technique for selected patients with simultaneous panurothelial carcinoma. Further multicentric studies are warranted to determine the safety of this minimally invasive approach in patients with different comorbidities.

Comparison of Outcomes between Standard and Palliative Management for High Grade Non-Muscle Invasive Bladder Cancer in Patients Older than 85 Years.

OBJECTIVES: To analyze outcomes of patients > 85 years with de novo bladder cancer (BCa). To compare outcomes of high grade (HG) non-muscle invasive BCa (NMIBC) treated with standard therapies versus palliative management. METHODS: Retrospective revision of 65 patients > 85 years who underwent transurethral resection of the bladder (TURB) for de novo BCa. According to functional status each patient was offered a standard or palliative management after TURB. RESULTS: Median age was 87.3 years (85.2-95.4) and 51 were men (78.5%). Twenty-eight (43%) were American Society of Anesthesiologists (ASA) II and 37 ASA III-IV (57%). Pathological examination: 29 pTx-pTa (44.6%), 28 pT1 (43.1%) and 8 pT2 (12.3%). Twenty were low grade (30.8%) and 45 HG (69.2%). Among 37 HG NMIBC patients, 43% followed standard therapies (BCG or re-staging TURB + BCG), and 57% a palliative management (no oncological treatments). With a median follow-up of 20 months (3-108), 2 (12.5%) died in standard group compared to 11 (52.4%) in palliative. In univariate analysis, age (p = 0.024), stage (p = 0.009), and standard management (p = 0.019) were related to overall survival (OS). In multivariate, standard management was an independent prognostic factor of OS (hazard ratio 0.164, 95% CI 0.036-0.744, p = 0.048). CONCLUSIONS: Advanced age should not be a contraindication for standard therapies in BCa. A geriatric assessment could identify patients who may benefit from adjuvant therapies after TURB.

Use of an acellular collagen-elastin matrix to support bladder regeneration in a porcine model of peritoneocystoplasty.

INTRODUCTION: Bladder reconstruction without using the intestine remains a challenge to this day despite the development of new biomaterials and cell cultures. Human bladder engineering is merely anecdotic, and mostly in vitro and animal studies have been conducted. MATERIAL AND METHODS: In our study using a porcine model, we performed a bladder augmentation using an autologous parietal peritoneum graft (peritoneocystoplasty) and determined whether the attachment of an acellular collagen-elastin matrix (Group 1) or lack of (Group 2) had better histologic and functional results. Thus far, peritoneocystoplasty has rarely been performed or combined with a biomaterial. RESULTS: After 6 weeks, we observed different degrees of retraction of the new bladder wall in both groups, although the retraction was lower and the histological analysis showed more signs of regeneration (neoangiogenesis and less fibrosis) in Group 1 than when compared with Group 2. No transitional cells were found in the new bladder wall in any of the groups, and no differences were observed in the functional test results. CONCLUSIONS: Performing a peritoneocystoplasty is an easy and safe procedure. The data supports the benefit of an acellular collagen-elastin matrix to reinforce bladder regeneration. However, in our study we observed too much retraction of the new wall and the histologic results were not acceptable to consider it an appropriate cystoplasty technique.

Comparison of the initial robot-assisted radical prostatectomy results with laparoscopic radical prostatectomy.

OBJECTIVES: To evaluate and compare the functional results of an established technique, laparoscopic radical prostatectomy(LRP), and the initial learning curve of robot assisted laparoscopic radical prostatectomy (RALRP). METHODS: This is a transversal case-control hybrid studio including all patients undergoing RALRP (39 ) and similar number of patients undergoing LRP (37) from November 2009 to June 2011. We used a transversal phone interrogatory to evaluate functional outcome. RESULTS: The groups were comparable for IMC, age, serum PSA, prostatic ultrasound volume, biopsy Gleason, following time and clinical stage. For operative variables, there was no difference in estimated blood loss, hospital stay, days of drainage, time to catheter removal, transfusion rate and surgical margins. Median operative time was 216 min for RALRP, and 153 min for LRP (p < 0,001). There were no differences in erectile function or continence at 12 months. Mean time to continence was 5.7 weeks in RALRP and 8.9 week in LRP (p < 0,001). There was no difference in time to normal erectile function. CONCLUSIONS: Even in the beginning of RALRP we did obtain results comparable to LRP.

Comparación de los resultados iniciales de la prostatectomía radical robótica frente a la laparoscopia convencional / Comparison of the initial robot-assisted radical prostatectomy results with laparoscopic radical prostatectomy

OBJETIVO: Evaluar y comparar los resultados funcionales entre una técnica estandarizada, la prostatectomía radical laparoscópica (PRL), y la curva de aprendizaje inicial de la prostatectomía radical laparoscópica asistida por robot (PRLaR). MÉTODOS: Este es un estudio de transversal híbrido de casos y controles de todos los pacientes sometidos a PRLaR (39) y un muestreo por densidad de similar número de pacientes sometidos a PRL (37), entre noviembre de 2009 y junio de 2011. Se realizó una encuesta telefónica transversal para evaluar los resultados funcionales. RESULTADOS: Los grupos fueron estadísticamente similares en cuanto a IMC, edad, PSA sérico, volumen prostático por ecografía, Gleason de la biopsia, tiempo de seguimiento y estadio clínico. En cuanto a variables quirúrgicas, no hubo diferencia en estimación de sangrado, estancia hospitalaria, días de drenaje, días de sonda vesical, transfusión sanguínea o márgenes quirúrgicos. El tiempo quirúrgico promedio fue de 216 min para la PRLaR y de 153 min para la PRL, (p<0,001). No hubo diferencia estadística en cuanto a función eréctil y continencia a los 12 meses. El tiempo de recuperación de continencia fue significativamente menor (p<0,001) en la PRLaR (5,7 sem) en comparación con la PRL (8,9 sem). No hubo diferencia en tiempo de recuperación de la función eréctil. CONCLUSIÓN: incluso en el inicio de la PRLaR obtuvimos resultados comparables a la PRL

OBJECTIVES: To evaluate and compare the functional results of an established technique, laparoscopic radical prostatectomy (LRP), and the initial learning curve of robot assisted laparoscopic radical prostatectomy (RALRP). METHODS: This is a transversal case-control hybrid studio including all patients undergoing RALRP (39) and similar number of patients undergoing LRP (37) from November 2009 to June 2011. We used a transversal phone interrogatory to evaluate functional outcome. RESULTS: The groups were comparable for IMC, age, serum PSA, prostatic ultrasound volume, biopsy Gleason, following time and clinical stage. For operative variables, there was no difference in estimated blood loss, hospital stay, days of drainage, time to catheter removal, transfusion rate and surgical margins. Median operative time was 216 min for RALRP, and 153 min for LRP (p<0,001). There were no differences in erectile function or continence at 12 months. Mean time to continence was 5.7 weeks in RALRP and 8.9 week in LRP (p<0,001). There was no difference in time to normal erectile function. CONCLUSIONS: Even in the beginning of RALRP we did obtain results comparable to LRP

Genetic predisposition to early recurrence in clinically localized prostate cancer.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Currently available nomograms to predict preoperative risk of early biochemical recurrence (EBCR) after radical prostatectomy are solely based on classic clinicopathological variables. Despite providing useful predictions, these models are not perfect. Indeed, most researchers agree that nomograms can be improved by incorporating novel biomarkers. In the last few years, several single nucleotide polymorphisms (SNPs) have been associated with prostate cancer, but little is known about their impact on disease recurrence. We have identified four SNPs associated with EBCR. The addition of SNPs to classic nomograms resulted in a significant improvement in terms of discrimination and calibration. The new nomogram, which combines clinicopathological and genetic variables, will help to improve prediction of prostate cancer recurrence. OBJECTIVES: To evaluate genetic susceptibility to early biochemical recurrence (EBCR) after radical prostatectomy (RP), as a prognostic factor for early systemic dissemination. To build a preoperative nomogram to predict EBCR combining genetic and clinicopathological factors. PATIENTS AND METHODS: We evaluated 670 patients from six University Hospitals who underwent RP for clinically localized prostate cancer (PCa), and were followed-up for at least 5 years or until biochemical recurrence. EBCR was defined as a level prostate-specific antigen >0.4 ng/mL within 1 year of RP; preoperative variables studied were: age, prostate-specific antigen, clinical stage, biopsy Gleason score, and the genotype of 83 PCa-related single nucleotide polymorphisms (SNPs). Univariate allele association tests and multivariate logistic regression were used to generate predictive models for EBCR, with clinicopathological factors and adding SNPs. We internally validated the models by bootstrapping and compared their accuracy using the area under the curve (AUC), net reclassification improvement, integrated discrimination improvement, calibration plots and Vickers' decision curves. RESULTS: Four common SNPs at KLK3, KLK2, SULT1A1 and BGLAP genes were independently associated with EBCR. A significant increase in AUC was observed when SNPs were added to the model: AUC (95% confidence interval) 0.728 (0.674-0.784) vs 0.763 (0.708-0.817). Net reclassification improvement showed a significant increase in probability for events of 60.7% and a decrease for non-events of 63.5%. Integrated discrimination improvement and decision curves confirmed the superiority of the new model. CONCLUSIONS: Four SNPs associated with EBCR significantly improved the accuracy of clinicopathological factors. We present a nomogram for preoperative prediction of EBCR after RP.

[Holmium laser enucleation of the prostatic adenoma]. / Enucleación del adenoma prostático mediante el láser de Holmio (HOLEP).

Holmium laser enucleation of the prostatic adenoma (HoLEP) represents an innovative surgical option for the treatment of bladder outlet obstruction caused by benign prostatic hypertrophy. The results of numerous randomized prospective studies and clinical case series have confirmed that HoLEP is a procedure that attains immediate bladder outlet obstruction release, that improvement of symptomatic and uroflowmetry parameters is maintained in the midterm and, it is associated with less morbidity than conventional surgery. On the other hand, the shortage of urologists with experience in this procedure, and its technical difficulty have limited its spread in our environment. In this article we describe in detail the technique we use in our center for the performance of HoLEP, emphasizing the modifications we have introduced with time to make the operation easier and to avoid complications.

Enucleación del adenoma prostático mediante el láser de holmio (HOLEP) / No disponible

La enucleación del adenoma prostático mediante el láser de holmio (HoLEP) representa una novedosa alternativa quirúrgica para el tratamiento de la obstrucción infravesical ocasionada por el crecimiento prostático benigno. Los resultados de numerosos estudios prospectivos aleatorizados y de series de casos clínicos han confirmado que HoLEP es un procedimiento que logra una desobstrucción infravesical inmediata, que la mejoría de los parámetros sintomáticos y flujométricos que consigue se mantiene a medio plazo y que se asocia a menor morbilidad que la cirugía convencional. Por contra, la escasez de urólogos con experiencia en el procedimiento y su dificultad técnica han limitado su difusión en nuestro medio. En el presente trabajo describimos detalladamente la técnica que empleamos en nuestro centro para la realización de HoLEP, haciendo hincapié en las modificaciones que hemos ido realizando con el tiempo para facilitar la cirugía y evitar las complicaciones(AU)

Holmium laser enucleation of the prostatic adenoma (HoLEP) represents an innovative surgical option for the treatment of bladder outlet obstruction caused by benign prostatic hypertrophy. The results of numerous randomized prospective studies and clinical case series have confirmed that HoLEP is a procedure that attains immediate bladder outlet obstruction release, that improvement of symptomatic and uroflowmetry parameters is maintained in the midterm and, it is associated with less morbidity than conventional surgery. On the other hand, the shortage of urologists with experience in this procedure, and its technical difficulty have limited its spread in our environment. In this article we describe in detail the technique we use in our center for the performance of HoLEP, emphasizing the modifications we have introduced with time to make the operation easier and to avoid complications(AU)

33% radius evaluation to assess bone mineral density in prostate cancer patients.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the standard method to assess bone mineral density (BMD). The International Society for Clinical Densitometry recommends the measurement of BMD at lumbar spine, total hip and femoral neck, but in certain circumstances the 33% radius may be the recommended area to measure BMD. The aim of this study has been to analyze whether 33% radius should be considered the recommended area to assess BMD in prostate cancer patients. METHODS: This is a retrospective study where BMD was assessed by DXA at 33% radius, lumbar spine, total hip, and femoral neck (cDXA) in 141 prostate cancer patients. Twenty-eight patients were hormone naïve while 113 were subjected to androgen suppression (AS) during the mean period of 29 months. Osteoporosis was diagnosed when T-score was lower than -2.5 and osteopenia when it ranged between -1 and -2.5. RESULTS: The osteoporosis rate was 29.8% at 33% radius, 23.4% at femoral neck, 19.9% at lumbar spine, and 12.8% at total hip. The overall osteoporosis rate at cDXA was 29.1%. Osteoporosis was detected in 52.2% at 33% radius and 36.2% at cDXA. Normal BMD was found in 17.7% at 33% radius and 34.8% at cDXA. The 33% radius was the only site where a significant increase in the osteoporosis rate was detected in patients subjected to AS compared to those hormone naïve (33 and 13.8%). CONCLUSIONS: The 33% radius seems more sensible than the central skeleton areas to detect bone mass loss in patients with prostate cancer.

Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

OBJECTIVE: An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. PATIENTS AND METHODS: The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). RESULTS: The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. CONCLUSIONS: The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PURPOSE: Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. RESULTS: The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. CONCLUSIONS: Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information.

Preoperative prediction of pathologically insignificant prostate cancer in radical prostatectomy specimens: the role of prostate volume and the number of positive cores.

INTRODUCTION: To determine clinical and biopsy features with predictive capacity to identify pathologically insignificant prostate cancer (pIPCa). MATERIAL AND METHODS: pIPCa was defined as cancer volume <0.5 cm(3) and a Gleason score (GS) of or=45 cm(3) to d'Amico's criteria. This allows to preoperatively distinguish between patients that most probably would benefit from radical treatment and patients that might be offered active surveillance.

Evaluation of the serum testosterone to prostate-specific antigen ratio as a predictor of prostate cancer risk.

OBJECTIVE: To analyse the ratio of serum testosterone (sT) to prostate-specific antigen (PSA) as a predictor of prostate cancer risk, as low levels of sT have been related to a greater risk of prostate cancer, and its ratio with serum PSA level was recently proposed as a new tool to increase the specificity of PSA. PATIENTS AND METHODS: In all, 439 consecutive men with a normal digital rectal examination and a serum PSA level of 4.1-20 ng/mL had a transrectal ultrasonography-guided biopsy using a 10-core scheme, with an additional 1-8 cores according to prostate volume and patient age. The sT level was determined before the procedure using a chemiluminescent assay, and the ratio of sT to PSA (sT/PSA) was calculated after transforming sT measurements from ng/dL to ng/mL. The percentage free PSA (%fPSA) and PSA density were also included in this analysis. RESULTS: The overall cancer detection rate was 42.1%. The median sT level was 469 ng/dL in men with cancer and 499 ng/dL in those without (P = 0.521). The median sT/PSA was 0.68 and 0.74, respectively (P = 0.215). However, the median %fPSA was 14 in men with cancer and 17 in men without (P < 0.001) and the median PSA density was 0.22 and 0.16, respectively (P < 0.001). The multivariate analysis confirmed the independent predictive value only for %fPSA (odds ratio 0.94, 95% confidence interval 0.91-0.98) and PSA density (5.8, 3.42-19.8). CONCLUSION: These results do not support the use of sT/PSA for predicting the risk of prostate cancer and to increase the specificity of PSA.

Risk factors for positive findings in patients with high-grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette-Guérin therapy and the decision for a repeat TUR.

OBJECTIVE: To determine factors predictive of positive findings at the 3-month follow-up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette-Guérin [BCG] therapy) in patients with initial high-grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy. PATIENTS AND METHODS: In all, 138 patients with initial HGT1-transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG-TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi-squared, Mann-Whitney U and multivariate logistic regression. RESULTS: Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG-TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG-TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002). CONCLUSIONS: In initial HGT1-TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1-TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five-fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.