Bladder cancer recurrence surveillance by urine metabolomics analysis.

Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence.

Cálculo del riesgo biológico de multirrecidiva y progresión del carcinoma urotelial no músculo-invasivo mediante nuevos modelos matemáticos / Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models

Objetivo: El carcinoma urotelial de vejiga no músculo-invasivo (CVNMI) se caracteriza por eventos repetidos en forma de recidiva tumoral o la aparición de progresión tumoral. La aplicación del modelo de Cox para analizar estos eventos no es válido, ya que los tiempos entre recurrencias de un mismo paciente pueden estar fuertemente correlacionados, y se requiere otro tipo de modelización matemática. El objetivo del estudio es aplicar nuevos modelos matemáticos apropiados a las características biológicas del CVNMI. Material y métodos: Novecientos sesenta pacientes con diagnóstico de CVNMI con una media de seguimiento de 48,1 (3-160) meses y validación del modelo con 240 pacientes de otro centro. Se realizó resección transuretral con biopsias aleatorias. Las variables analizadas fueron: número y tamaño tumoral, edad, tratamiento adyuvante y características anatomopatológicas del tumor (grado y estadio). Para el análisis estadístico se utilizaron extensiones del modelo de Cox como el modelo de fragilidad conjunta para la multirrecidiva y progresión tumoral. Para la validación del modelo se utilizó el índice de concordancia. Resultados: Cuatrocientos sesenta y ocho (48,8%) pacientes tuvieron una recidiva tumoral y 52 (5,4%) presentaron progresión tumoral. Las variables que formaron parte del modelo para múltiple recidiva fueron la edad, el grado, el número, el tratamiento empleado y el número previo de recidivas, mientras que para progresión fueron la edad, el estadio y el grado. El índice de concordancia fue 0,64 para la multirrecidiva y 0,85 para la progresión. Conclusión: La alta concordancia obtenida y la validación con una fuente externa permite predecir con mayor precisión el riesgo de multirrecidiva y progresión

Objective: To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. Materials and methods: 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). Results: 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. Conclusion: the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases

Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

OBJECTIVE: To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. MATERIALS AND METHODS: 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). RESULTS: 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. CONCLUSION: the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases.

Reconstrucción del glande con injerto cutáneo libre según técnica de Bracka / Reconstruction of the Glans With Free-Skin Graft Applying the Bracka Technique

Introducción: Analizamos nuestra experiencia en el manejo conservador y reconstructivo de los pacientes tratados de cáncer de pene y/o patologías cutáneas del pene en nuestra institución. Material y métodos: Hemos revisado retrospectivamente todos los procedimientos de injerto cutáneo realizados en la cirugía peneana a lo largo de los últimos 8 años. Se presentan las indicaciones y resultados de estas cirugías y el procedimiento quirúrgico detallado descrito originalmente por Bracka. Resultados: Diez pacientes fueron sometidos a extirpación parcial del pene seguida de técnica quirúrgica reconstructiva con injerto libre de piel creando un neoglande. No se han registrado casos de complicaciones mayores; dos pacientes tuvieron pérdida parcial del injerto y ninguno ha presentado recidiva local. Seis pacientes comunicaron haber reanudado su actividad sexual después de la curación completa. Conclusión: Existe un grupo importante de pacientes con cáncer de pene y/o otras patologías en el glande donde es posible realizar una cirugía reconstructiva peneana no mutilante con resultados oncológicos, estéticos y funcionales satisfactorios (AU)

Introduction: We analyse our experience in the conservative surgical management of penile cancer and/or penile skin pathologies at our institution. Material and methods: We have retrospectively reviewed all the skin grafting procedures performed in penile surgery in the last eight years. We show the indications and results of these surgical procedures and the detailed surgical technique originally described by Bracka. Results: Ten patients had several types of partial penile removal surgery followed by free-skin graft resurfacing, creating a neoglans. There were no relevant or major complications; two patients suffered partial necrosis of the skin graft. There was no local recurrence. 6 Patients returned to normal sexual activity after complete healing. Conclusions: There is a significant number of patients with penile cancer and/or other penile skin pathologies who can undergo definitive and non-mutilating surgery with excellent oncologic, cosmetic and functional results with skin grafting (AU)

[Reconstruction of the glans with free-skin graft applying the Bracka technique]. / Reconstrucción del glande con injerto cutáneo libre según técnica de Bracka.

INTRODUCTION: We analyse our experience in the conservative surgical management of penile cancer and/or penile skin pathologies at our institution. MATERIAL AND METHODS: We have retrospectively reviewed all the skin grafting procedures performed in penile surgery in the last eight years. We show the indications and results of these surgical procedures and the detailed surgical technique originally described by Bracka. RESULTS: Ten patients had several types of partial penile removal surgery followed by free-skin graft resurfacing, creating a neoglans. There were no relevant or major complications; two patients suffered partial necrosis of the skin graft. There was no local recurrence. 6 Patients returned to normal sexual activity after complete healing. CONCLUSIONS: There is a significant number of patients with penile cancer and/or other penile skin pathologies who can undergo definitive and non-mutilating surgery with excellent oncologic, cosmetic and functional results with skin grafting.

Expresión inmunohistoquímica de la densidad microvascular y de la anhidrasa carbónica IX en carcinoma renal. Relación con el tipo histológico y con la progresión tumoral / Immunohistochemical expression of microvascular density and carbonic anhidrase IX in renal carcinoma. Relation to histological type and tumoral progression

Objetivos: relacionar la expresión inmunohistoquímica (IHQ) de la densidad microvascular (DMV) y de la anhidrasa carbónica IX (ACIX) con los tipos histológicos de carcinoma renal (CR) y con su progresión. Material y métodos: se estudiaron 93 pacientes operados por CR entre 1990-2008. Anticuerpos: CD31 (1: 40, Dako) y CD34 (1: 50, Dako) para DMV y ACIX (1: 100, Santa Cruz). ACIX se valoró semicuantitativamente; intensamente positivos (>85%), débilmente positivos (10-85%) y negativos (< 10%), independientemente de la intensidad de la tinción. La DMV se valoró independientemente con anti-CD31 y anti-CD34. Campo de bajo aumento (x100) con mayor densidad de vasos teñidos; se contabilizó el número de vasos en un campo fotográfico de 0,53mm2. Resultados expresados como número máximo de vasos/ mm2 de tejido tumoral. Resultados: mediana seguimiento; 40 meses (1-160). No encontramos diferencias IHQ para ninguno de los 3 marcadores entre tumores que progresan (49) y no progresan (44). La expresión de ACIX estaba relacionada con la DMV (p<0,0001). La DMV se relacionó inversamente con el tamaño tumoral y con el grado de Fuhrman de forma significativa. Así mismo, fue significativamente mayor en los CR de células claras, tanto medida con CD31 (p=0,001) como con CD34 (p=0,003) frente al resto de subtipos histológicos. Conclusiones: la DMV y la expresión de ACIX no se relacionan con la progresión, pero sí con el tipo tumoral. Ello y su coexpresividad permitiría usar la expresión de ACIX como medida orientativa rápida y fácil para medir DMV y su posible relación con la respuesta a antiangiogénicos (AU)

Purpose: to correlate the immunohistochemical expression of microvascular density (MVD) and the carbonic anhydrase IX (CAIX) with the different histological subtypes of renal carcinoma and its progression. Material and methods: we studied 93 patients with renal cell carcinoma operated between 1990 and 2008. Antibodies employed for immunohistochemistry (IHC); CD31 (1: 40, Dako) and CD34 (1: 50, Dako) for MVD and CAIX (1: 100, Santa Cruz). CAIX was validated semiquantitatively as: strongly positive (>85%); weakly positive (10% -85%); and negative (< 10%), independently of the intensity of the stain. MVD was validated with both anti-CD31 and anti-CD34 by means of a whole section, to select the microscopic field (x100) with highest density of stained vessels, counting the number of vessels in a photographic field of 0.53mm2. Results are expressed as the maximal number of vessels by mm2 of tumour tissue. Results: median follow up was 40 months (1-160). We found no differences of expression with any of the 3 IHC markers between tumours that progressed (49) and tumours that did not progress (44). The IHC expression of CAIX was strongly related to MVD, measured for both CD31 and CD34 (p<0.0001). MVD with both antibodies was inversely related to tumour size and Fuhrman grade and was also stronger in clear cell carcinomas compared to the rest of histological subtypes, measured by CD31 (p=0.001) and CD34 (p=0.003). Conclusions: neither MVD nor CAIX expressions were related to tumour progression, but were related to histological subtypes. This fact, added to their co-expression, could prompt the use of the CAIX expression, which is far more reproducible, as a quick and easy approximation to MVD. More research should be done to use it as marker for targeted therapy (AU)

[Immunohistochemical expression of microvascular density and carbonic anhidrase IX in renal carcinoma. Relation to histological type and tumoral progression]. / Expresión inmunohistoquímica de la densidad microvascular y de la anhidrasa carbónica IX en carcinoma renal. Relación con el tipo histológico y con la progresión tumoral.

PURPOSE: to correlate the immunohistochemical expression of microvascular density (MVD) and the carbonic anhydrase IX (CAIX) with the different histological subtypes of renal carcinoma and its progression. MATERIAL AND METHODS: we studied 93 patients with renal cell carcinoma operated between 1990 and 2008. Antibodies employed for immunohistochemistry (IHC); CD31 (1: 40, Dako) and CD34 (1: 50, Dako) for MVD and CAIX (1: 100, Santa Cruz). CAIX was validated semiquantitatively as: strongly positive (>85%); weakly positive (10% -85%); and negative (< 10%), independently of the intensity of the stain. MVD was validated with both anti-CD31 and anti-CD34 by means of a whole section, to select the microscopic field (x100) with highest density of stained vessels, counting the number of vessels in a photographic field of 0.53 mm(2). Results are expressed as the maximal number of vessels by mm(2) of tumour tissue. RESULTS: median follow up was 40 months (1-160). We found no differences of expression with any of the 3 IHC markers between tumours that progressed (49) and tumours that did not progress (44). The IHC expression of CAIX was strongly related to MVD, measured for both CD31 and CD34 (p<0.0001). MVD with both antibodies was inversely related to tumour size and Fuhrman grade and was also stronger in clear cell carcinomas compared to the rest of histological subtypes, measured by CD31 (p = 0.001) and CD34 (p = 0.003). CONCLUSIONS: neither MVD nor CAIX expressions were related to tumour progression, but were related to histological subtypes. This fact, added to their co-expression, could prompt the use of the CAIX expression, which is far more reproducible, as a quick and easy approximation to MVD. More research should be done to use it as marker for targeted therapy.

Progresión metastática, mortalidad cáncer específica y necesidad de tratamientos de segunda línea en pacientes con cáncer de próstata de alto riesgo tratados inicialmente mediante prostatectomía radical / Metastatic progression, cancer-specific mortality and need for secondary treatments in patients with clinically high-risk prostate cancer treated initially with radical prostatectomy

Objetivos: Determinar nuestros resultados en pacientes con cáncer de próstata (CaP) de alto riesgo (AR) tratados mediante prostatectomía radical (PR) y establecer criterios pronósticos preoperatorios. Material y métodos: Estudio retrospectivo de 925 PR. El seguimiento medio fue 89,8+/−53,6 meses para el grupo de CaP de AR. Siguiendo los criterios NCCN, operamos 210 (22,7%) PR de AR y 715 (77,3%) de riesgo bajo/intermedio. Se utilizó el método Kaplan-Meier para análisis de supervivencia y el modelo de Cox para el análisis multivariado de factores pronósticos para progresión metastática. Resultados: Periodo revisado; 1986–2007. Cincuenta y cuatro pacientes de AR (25,7%) estaban libres de progresión y 8 pacientes (3,8%) murieron por otras causas libres de enfermedad. El CaP progresó en 148 pacientes (70,5%). Murieron por progresión tumoral 42 pacientes (20%) y por otras causas 25 pacientes (11,9%). Setenta y nueve pacientes de AR (38%) frente a 549 de riesgo bajo/intermedio (78,5%) no necesitaron más líneas de tratamiento (p<0,001). Los análisis uni y multivariados demostraron que tanto el score Gleason en biopsia (RR=1,922; 95% CI 1,106–3,341, p=0,020) como el estadio clínico (RR=2,290; 95% CI 1,269–4,133, p=0,006) mostraron valor pronóstico independiente para progresión metástasica, pero no el PSA. Conclusiones: Un paciente con CaP de AR que se opere tiene un 25% de posibilidades de curarse y podrá necesitar un tratamiento multimodal en más de la mitad de los casos. Recomendamos PR en un paciente joven si el tumor se considera resecable, sobre todo si el único factor pronóstico que lo encasilla como AR es la elevación del PSA (AU)

Purpose: To determine our results in high risk (HR) prostate cancer (PCa) patients treated with radical prostatectomy (RP) and to establish preoperative prognosis factors. Material and methods: Retrospective study of 925 RP. Mean follow-up for the HR group was 89.8+/−53.6 months. Following NCCN criteria, we operated 210 (22.7%) HR and 715 (77.3%) low/intermediate risk patients. End point was metastatic progression. Kaplan-Meier method for survival comparison among groups and Cox regression model for multivariate analysis of preoperative prognostic factors were used. Results: Revised period; 1986–2007. Fifty-four patients (25.7%) were free of disease and 8 patients (3.8%) died for other causes free of disease. Disease progressed in 148 patients (70.5%); death due to tumour progression occurred in 42 cases (20%) and due to other causes in 25 patients (11.9%). Seventy-nine patients in HR group (38%) vs 549 low/intermediate risk group (78.5%) did not deserve further treatments (p<0.001). The uni and multivariate analysis for metastatic progression showed both Gleason score at biopsy (RR=1.922; 95% CI 1.106–3.341, p=0.020) and clinical stage (RR=2.290; 95% CI 1.269–4.133, p=0.006) showed independent prognostic value for metastatic progression, but not PSA. Conclusions: A HR patient can be cured in a third of the cases and will need multimodal treatments in more than half of the times. We prompt surgery in a young healthy patient with a resectable tumour, mainly if just one bad prognostic factor is present and defiantly if this is just PSA elevation (AU)

[Metastatic progression, cancer-specific mortality and need for secondary treatments in patients with clinically high-risk prostate cancer treated initially with radical prostatectomy]. / Progresión metastática, mortalidad cáncer específica y necesidad de tratamientos de segunda línea en pacientes con cáncer de próstata de alto riesgo tratados inicialmente mediante prostatectomía radical.

PURPOSE: To determine our results in high risk (HR) prostate cancer (PCa) patients treated with radical prostatectomy (RP) and to establish preoperative prognosis factors. MATERIAL AND METHODS: Retrospective study of 925 RP. Mean follow-up for the HR group was 89.8+/-53.6 months. Following NCCN criteria, we operated 210 (22.7%) HR and 715 (77.3%) low/intermediate risk patients. End point was metastatic progression. Kaplan-Meier method for survival comparison among groups and Cox regression model for multivariate analysis of preoperative prognostic factors were used. RESULTS: Revised period; 1986-2007. Fifty-four patients (25.7%) were free of disease and 8 patients (3.8%) died for other causes free of disease. Disease progressed in 148 patients (70.5%); death due to tumour progression occurred in 42 cases (20%) and due to other causes in 25 patients (11.9%). Seventy-nine patients in HR group (38%) vs 549 low/intermediate risk group (78.5%) did not deserve further treatments (p<0.001). The uni and multivariate analysis for metastatic progression showed both Gleason score at biopsy (RR=1.922; 95% CI 1.106-3.341, p=0.020) and clinical stage (RR=2.290; 95% CI 1.269-4.133, p=0.006) showed independent prognostic value for metastatic progression, but not PSA. CONCLUSIONS: A HR patient can be cured in a third of the cases and will need multimodal treatments in more than half of the times. We prompt surgery in a young healthy patient with a resectable tumour, mainly if just one bad prognostic factor is present and defiantly if this is just PSA elevation.

[Significance of residual hyperplastic cells after radical prostatectomy. A literature review]. / Trascendencia de células hiperplásicas residuales a la prostatectomía radical. Revisión de la literatura.

INTRODUCTION: Radical prostatectomy represents a standard surgical treatment for clinically localized prostate cancer. Classically pathologist and urologist worried about positive surgical margin, but not to the presence of surgery residual hyperplastic cells able to generate prostate specific antigen (PSA) and difficult the follow up of the patients that underwent surgery. We reviewed the literature looking for the incidence, the potential etiology and the influence of these hyperplastic cells in the biochemical evolution of the disease. MATERIAL AND METHOD: The information for this review was compiled by searching the Pubmed database. We used "Mesh", Prostatectomy" and "Prostatic Neoplasms" and "Prostate-Specific Antigen" terms, and we added "biochemical failure" and/or "hyperplasic cells" and/or "benign cells". Furthermore, we select the work in English, Spanish and German, review articles that referenced this work and include the series with more than 50 patients, letters to the editor, editorials and overall reviews. CONCLUSIONS: Benign hyperplasic cells left behind after radical prostatectomy are frequent and probably under-rated. The influence of those cells in the biochemical outcome is a controversial issue. Positive margins for benign cells can come from apex or neck of the bladder, where the prostatic capsule is not well defined, but no from dorso-lateral area, this would imply a technical mistake. We recommend the inspection of the specimen by the surgeon, after prostatectomy in order to detect apex integrity, cranial and dorso-lateral capsule.

Trascendencia de células hiperplásicas residuales a la prostatectomía radical. Revisión de la Literatura / Significance of residual hyperplastic cells after radical prostatectomy. A literature review

Introducción: La Prostatectomía radical es el tratamiento estándar para el cáncer de próstata órgano confinado. Clásicamente se presta atención a los márgenes positivos para células tumorales, pero no a la presencia de células hiperplásicas residuales a la cirugía capaces de generar antígeno prostático específico (PSA) y dificultar el seguimiento de los pacientes intervenidos. Esta situación nos lleva a plantear una revisión de la literatura, donde evaluemos la frecuencia de esta presencia, las posibles causas que lo justifiquen y la influencia de estas células en la evolución bioquímica de la enfermedad. Material y Método: Realizamos una búsqueda bibliográfica a través de la base de datos 'Pubmed' utilizando los términos 'Mesh' 'Prostatectomy' y 'Prostatic Neoplasms' y 'Prostate-Specific Antigen' a los que añadimos los términos 'biochemical failure' y/o 'hyperplasic cells' y/o 'benign cells' . Así mismo, seleccionamos los trabajos en lengua inglesa, española y alemana, revisamos los artículos que dichos trabajos referencian e incluimos las series con más de 50 pacientes, cartas al editor, editoriales y revisiones de conjunto. Conclusiones: La presencia de células hiperplásicas microscópicas residuales a la cirugía prostática radical, es un hecho frecuente que probablemente esté infra-evaluado. Los márgenes positivos para células benignas procederán de lápex o del cuello vesical donde la cápsula prostática no está bien definida, en ningún caso de la zona dorsolateral de la próstata, lo que traduciría un defecto de la técnica quirúrgica. La capacidad de estas células para generar PSA en cantidad suficiente para interferir en el seguimiento de los pacientes operados es controvertida. Recomendamos la inspección macroscópica de la pieza por el cirujano, tras la prostatectomía, para evaluar la integridad del ápex, zona craneal y cápsula dorsolateral (AU)

Introduction: Radical prostatectomy represents a standard surgical treatment for clinically localized prostate cancer. Classically pathologist and urologist worried about positive surgical margin, but not to the presence of surgery residual hyperplastic cells able to generate prostate specific antigen (PSA) and difficult the follow up of the patients that underwent surgery. We reviewed the literature looking for the incidence, the potential etiology and the influence of these hyperplastic cells in the biochemical evolution of the disease. Material and Method: The information for this review was compiled by searching the Pubmed database. We used 'Mesh', 'Prostatectomy' and 'Prostatic Neoplasms' and 'Prostate-Specific Antigen' terms, and we added 'biochemical failure' and/or 'hyperplasic cells' and/or 'benign cells'. Furthermore, we select the work in English, Spanish and German, review articles that referenced this work and include the series with more than 50 patients, letters to the editor, editorials and overall reviews. Conclusions: Benign hyperplasic cells left behind after radical prostatectomy are frequent and probably under-rated. The influence of those cells in the biochemical outcome is a controversial issue. Positive margins for benign cells can come from apex or neck of the bladder, where the prostatic capsule is not well defined, but no from dorso-lateral area, this would imply a technical mistake. We recommend the inspection of the specimen by the surgeon, after prostatectomy in order to detect apex integrity, cranial and dorso-lateral capsule (AU)

[A preliminar mathematical model for patients with a previous negative prostate biopsy]. / Desarrollo de un Modelo Matemático preliminar para la detección de cancer de próstata en los pacientes con biopsias prostáticas de repetición.

INTRODUCTION AND OBJECTIVES: It is usual to identify patients with a negative prostate biopsy who are still at risk of prostate cancer. We try to analyse if the classical variables used in the prostate cancer screening are useful for those patients with a previous negative prostate biopsy, and if there is a possibility for making a nomogram witch would help us in the decision to repeat the biopsy. MATERIAL AND METHODS: We studied 179 patients with at least 1 initial negative biopsy. At each biopsy session we recorded: Patient age, serum prostate specific antigen (PSA), free PSA/total PSA, PSA slope, digital rectal examination, prostate volume, PSA density, cancer suspicion in previous transrectal ultrasounds findings, number of negative cores previously obtained, history of precarcinomatous lesions and time between biopsies. Through Logistic regression analysis we determined the association of each variable a positive biopsy. A nomogram was constructed using all variables and discrimination was calculated as the concordance index. RESULTS: Overall 46% of patients had cancer at the repeated biopsy session. In the univariate analysis: Age, digital rectal examination, prostate volume, PSA density, cancer suspicion in ultrasounds findings, and precarcinomatous lesions were associated with repeat positive biopsy for cancer (all p <0.05). In the multivariate study, age, digital rectal examination, prostate volume and history of precarcinomatous lesions were associated with repeat positive biopsy. A nomogram was constructed that had a concordance index of 0.80.