Determination of TMPRSS2-ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis.

Prostate cancer (PCa) is one of cancer with of the highest incidence and mortality worldwide. Current disease prognostic markers do not differentiate aggressive from indolent PCa with sufficient certainty, and characterization by molecular subtypes has been sought to allow a better classification. TMPRSS2-ERG, SPOP, FOXA1, and IDH1 molecular subtypes have been described, but the association of these subtypes with prognosis in PCa is unclear; their frequency in Colombian patients is also unknown. Formalin-fixed and paraffin-embedded samples of radical prostatectomy from 112 patients with PCa were used. The TMPRSS2-ERG subtype was assessed with fluorescent in situ hybridization. The mutations in SPOP, FOXA1, and IDH1 in hot-spot regions were evaluated using Sanger sequencing. Fusion was detected in 71 patients (63.4%). No statistically significant differences were found between the state of fusion and the variables analyzed. In the 41 fusion-negative cases (36.6%), two patients (4.9%) had missense mutations in SPOP (p.F102C and p.F133L), representing a 1.8% of the overall cohort. The low frequency of this subtype in Colombians could be explained by the reported variability in the frequency of these mutations according to the population (5%-20%). No mutations were found in FOXA1 in the cases analyzed. The synonym SNP rs11554137 IDH1105GGT was found in tumor tissue but not in the normal tissue in one case. A larger cohort of Colombian PCa patients is needed for future studies to validate these findings and gain a better understanding of the molecular profile of this cancer in our population and if there are any differences by Colombian regions.

Determination of ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes to evaluate their association with clonal origin and disease progression in multifocal prostate cancer.

BACKGROUND: The prognostic relevance of prostate cancer (PCa) molecular subtypes remains controversial, given the presence of multiple foci with the possibility of different subtypes in the same patient. AIM: To determine the clonal origin of heterogeneity in PCa and its association with disease progression, SPOP, ERG(+), EZH2, NKX3.1, and SPINK-1 subtypes were analyzed. METHODS: A total of 103 samples from 20 PCa patients were analyzed; foci of adjacent non-tumor prostate tissue, HGPIN, GL3, GL4, GL5, and LN were examined to determine the presence of the TMPRSS2-ERG fusion and ERG, EZH2, NKX3.1, and SPINK-1 expression levels, using RT-PCR. Mutations in exons 6 and 7 of the SPOP gene were determined by sequencing. The presence of subtypes and molecular patterns were identified by combining all subtypes analyzed. To establish the clonal origin of multifocal PCa, molecular concordance between different foci of the same patient was determined. Association of these subtypes with histopathological groups and time to biochemical recurrence (BCR) was assessed. RESULTS: No mutation was found in SPOP in any sample. The ERG(+) subtype was the most frequent. The molecular pattern containing all four PCa subtypes was only detected in 3 samples (4%), all LN, but it was the most frequent (40%) in patients. Molecular discordance was the predominant status (55%) when all analyzed molecular characteristics were considered. It was possible to find all subtypes, starting as a preneoplastic lesion, and all but one LN molecular subtype were ERG(+) and NKX3.1 subtypes. Only the expression of the NKX3.1 gene was significantly different among the histopathological groups. No association was found between BCR time in patients and molecular subtypes or molecular concordance or between clinicopathological characteristics and molecular subtypes of ERG, EZH2, and SPINK-1. CONCLUSION: The predominance of molecular discordance in prostatic foci per patient, which reflects the multifocal origin of PCa foci, highlights the importance of analyzing multiple samples to establish the prognostic and therapeutic relevance of molecular subtypes in a patient. All the subtypes analyzed here are of early onset, starting from preneoplastic lesions. NKX3.1 gene expression is the only molecular characteristic that shows a progression pattern by sample.

Social Appropriation of Knowledge About Research in Prostate Cancer with Middle Education Students in Three Colombian Cities.

In Colombia, prostate cancer (PCa) is the most common cancer for incidence and mortality in men, which turns it into a public health problem. For high-risk communities to better understand the usefulness of basic research about PCa, a strategy of social appropriation of knowledge (SAK) in science and cancer was designed and implemented. A pedagogical activity and two tests (a pre-test and a post-test) were applied to middle education students in four schools in three Colombian cities to identify previous knowledge of biology concepts and cancer perceptions. As for biology concepts, there was a statistically significant increase (p < 0.01) in the total results of all questions in the post-test, especially in items related to the structure of DNA, differences between RNA and DNA, and codon. Similarly, better success rates were observed in questions about replication and mutation, and a statistically significant improvement related to the definition of cancer, cancer prevention, and its association with culture or ethnicity (p < 0.01). The results of the open question show what students learned about or were interested in the most, as evidence of the exchange of knowledge in those cities and the social appropriation of knowledge about PCa in Colombia. These findings show that this type of intervention, in diverse social contexts, is essential to improve understanding and perceptions that link school and scientific knowledge to a real problem, such as health and, in this case, cancer.

Concordancia de la clasificación VI-RADS® y la patología en espécimen de cistectomía en un centro oncológico colombiano / Concordance of VI-RADS® classification and pathology in cystectomy specimen in a Colombian oncology center

Objetivo: El objetivo principal de este estudio es evaluar la concordancia del reporte de la clasificación Vesical Imaging-Reporting and Data System (VI-RADS®) en resonancia magnética (RM) y el reporte de patología del espécimen de cistectomía y definir si este estudio puede considerarse un estándar en el proceso de estadificación en el paciente con diagnóstico clínico de cáncer de vejiga. Método: Estudio analítico retrospectivo de corte transversal, se incluyeron 34 pacientes llevados a cistectomía radical o parcial a quienes se realizó RM multiparamétrica prequirúrgica y se realizó un estudio de concordancia entre la clasificación VI-RADS® y el resultado de patología. Todas las resonancias fueron leídas y revisadas por un único radiólogo institucional. Resultados: El estudio de concordancia como resultado principal mostró un área bajo la curva para VI-RADS® ≥ 4 y resultado patológico positivo para compromiso muscular de 0,84, con una sensibilidad del 89.3% y especificidad del 50%, demostrando la adecuada precisión diagnóstica de la prueba. Conclusiones: La clasificación VI-RADS® es una herramienta de diagnóstico caracterizada por un excelente rendimiento diagnóstico cuando se evalúa la concordancia con el reporte de la patología final en el espécimen de la cistectomía.

Objective: The main objective of this study is to assess the concordance of the magnetic resonance imaging (MRI) Vesical Imaging-Reporting and Data System (VI-RADS®) classification report and the pathology report of the cystectomy specimen and to define whether this study can be considered a standard in the staging process in patients with a diagnosis of bladder cancer. Method: Retrospective, cross-sectional analytical study that included 34 patients undergoing radical or partial cystectomy who underwent pre-surgical multiparametric MRI. A concordance study was performed between the VI-RADS® classification and the pathology result. All MRIs were read and reviewed by a single institutional radiologist. Results: The concordance study as the main result showed an area under the curve for VI-RADS® ≥ 4 and a positive pathological result for muscle involvement of 0.84, with a sensitivity of 89.3% and a specificity of 50%, demonstrating the adequate diagnostic accuracy of the test. Conclusions: The VI-RADS® classification is a diagnostic tool characterized by excellent diagnostic performance when evaluating the agreement with the final pathology report in the cystectomy specimen.

[Predictors of biochemical recurrence after radical prostatectomy at an oncology reference center in Colombia.] / Factores predictores de recaída bioquímica después de prostatectomía radical en un centro oncológico colombiano.

OBJECTIVE: To determine predictors of BCR in patients with localized PCa undergoing RP at an oncology reference center in Colombia. MATERIALS AND METHODS: A retrospective analytical study was conducted on patients with localized PCa undergoing RP and who at least had one adverse pathological factor for BCR. We consider BCR as two consecutive elevations of PSA after RP, greater than 0.2 ng/ml. For the bivariate analysis we used Kaplan-Meier, and Cox proportional risk analysis to estimate the hazard ratio as well as to determine variables independently associated with the outcome. RESULTS: 280 patients were included. The medianage was 65.3 years, with a median follow up of 52.2 months. BCR occurred in 39% of patients, with a median BCR time of 24.8 months. In the multivariate analysis, high risk [HR 2.07 (95% CI 1.11 - 3.86)], positive surgical margins [HR 2.79 (95% CI 1.66 - 4.69)] and tertiary Gleason pattern [HR 2.16 (95% CI 1.16 - 4.01)] were identified as independent variables associated significantly with BCR. Limitations include retrospective design and sample size. CONCLUSIONS: High risk, positive surgical margins and the presence of tertiary Gleason pattern are the predictive factors of BCR after RP in the Colombian population.

OBJETIVO: Determinar los predictores de recaída bioquímica en pacientes con cáncer de próstata localizado llevados a prostatectomía radical en un centro oncológico de referencia en Colombia.MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo analítico en pacientes con cáncer de próstata localizado que fueron llevados a prostatectomía radical y que tuvieran al menos un factor patológico adverso para recaída bioquímica. Las variables analizadas fueron la edad, el riesgo, el estadio pT, el estadio pN, la densidad ganglionar, los márgenes quirúrgicos, el grupo grado de Gleason y el patrón terciario del Gleason. Consideramos recaída bioquímica como 2 elevaciones consecutivas del PSA después de la prostatectomía radical, mayor a 0,2 ng/ml. Para el análisis bivariado usamos Kaplan-Meier y el análisis de riesgo proporcional de Cox para estimar el HR así como para determinarlas variables independientemente asociadas con el desenlace. RESULTADOS: Se incluyeron 280 pacientes. La edad promedio fue de 65,3 años, con una media de seguimiento de 52,2 meses. La recaída bioquímica ocurrió en el 39% de los pacientes, con una media de tiempo hasta la recaída bioquímica de 24,8 meses. En el análisis multivariado, el riesgo alto [HR 2,07 (IC95% 1,11­ 3,86)], los márgenes quirúrgicos positivos [HR 2,79 (IC95% 1,66 ­ 4,69)] y el patrón terciario del Gleason [HR 2,16 (IC 95% 1,16 ­ 4,01)] fueron identificados como variables independientes asociadas significativamente con recaída bioquímica. Las limitaciones incluyen el diseño retrospectivo del estudio y el tamaño de la muestra. CONCLUSIONES: El riesgo alto, los márgenes quirúrgicos positivos y la presencia de patrón terciario de Gleason son las variables predictoras de recaída bioquímica después de prostatectomía radical en la población colombiana.

Factores predictores de recaída bioquímica después de prostatectomía radical en un centro oncológico colombiano / Predictive factors of biochemical relapse after radical prostatectomy in a Colombian cancer center

Objetivo: Determinar los predictores derecaída bioquímica en pacientes con cáncer de próstata localizado llevados a prostatectomía radical en uncentro oncológico de referencia en Colombia.Materiales y métodos: Se realizó un estudio retrospectivo analítico en pacientes con cáncer de próstatalocalizado que fueron llevados a prostatectomía radicaly que tuvieran al menos un factor patológico adversopara recaída bioquímica. Las variables analizadas fueron la edad, el riesgo, el estadio pT, el estadio pN, ladensidad ganglionar, los márgenes quirúrgicos, el grupo grado de Gleason y el patrón terciario del Gleason. Consideramos recaída bioquímica como 2 elevacionesconsecutivas del PSA después de la prostatectomía radical, mayor a 0,2 ng/ml. Para el análisis bivariado usamos Kaplan-Meier y el análisis de riesgo proporcionalde Cox para estimar el HR así como para determinarlas variables independientemente asociadas con el desenlace.Rresultados: Se incluyeron 280 pacientes. La edadpromedio fue de 65,3 años, con una media de seguimiento de 52,2 meses. La recaída bioquímica ocurrióen el 39% de los pacientes, con una media de tiempohasta la recaída bioquímica de 24,8 meses. En el análisis multivariado, el riesgo alto [HR 2,07 (IC95% 1,11– 3,86)], los márgenes quirúrgicos positivos [HR 2,79(IC95% 1,66 – 4,69)] y el patrón terciario del Gleason[HR 2,16 (IC 95% 1,16 – 4,01)] fueron identificadoscomo variables independientes asociadas significativamente con recaída bioquímica. Las limitaciones incluyenel diseño retrospectivo del estudio y el tamaño de lamuestra.Conclusiones: El riesgo alto, los márgenes quirúrgicos positivos y la presencia de patrón terciario deGleason son las variables predictoras de recaída bioquímica después de prostatectomía radical en la población colombiana.(AU)

Objetive: To determine predictors ofBCR in patients with localized PCa undergoing RP at anoncology reference center in Colombia.Materiales ymethods: A retrospective analyticalstudy was conducted on patients with localized PCa undergoing RP and who at least had one adverse pathological factor for BCR. We consider BCR as two consecutive elevations of PSA after RP, greater than 0.2 ng/ml.For the bivariate analysis we used Kaplan-Meier, andCox proportional risk analysis to estimate the hazardratio as well as to determine variables independentlyassociated with the outcome.Results: 280 patients were included. The medianage was 65.3 years, with a median follow up of 52.2months. BCR occurred in 39% of patients, with a median BCR time of 24.8 months. In the multivariate analysis,high risk [HR 2.07 (95% CI 1.11 – 3.86)], positive surgical margins [HR 2.79 (95% CI 1.66 – 4.69)] and tertiary Gleason pattern [HR 2.16 (95% CI 1.16 – 4.01)were identified as independent variables associatedsignificantly with BCR. Limitations include retrospectivedesign and sample size.Conclusions: High risk, positive surgical marginsand the presence of tertiary Gleason pattern are thepredictive factors of BCR after RP in the Colombian population.(AU)

Clinical and Histopathological Characteristics of Prostate Cancer Patients Taken to Palliative Transurethral Prostate Resection.

Introduction In prostate cancer (PCa) patients who have been treated with radiotherapy and/or androgen deprivation therapy (ADT), palliative transurethral resection of the prostate (TURP) is a management option in the presence of lower urinary tract symptoms (LUTS). The present work seeks to describe the clinical and histopathological characteristics of patients with PCa taken to palliative TURP. Methods An observational, descriptive and retrospective study of patients with PCa who underwent palliative TURP for the relief of obstructive urinary symptoms at an oncology reference center between January 2006 and June 2014 was performed. Among the included patients were those with localized PCa treated with radiotherapy and those with advanced PCa with or without metastasis who had previously received ADT. Results Sixty-six patients with a diagnosis of PCa taken to palliative RTUP were identified. Fifty patients (78.4%) were received some type of ADT, seven patients (10.7%) received curative radiotherapy along with adjuvant ADT, five patients (7.8%) were previously treated with only radiotherapy, and two patients (3.1 %) had received no prior management and thus were taken to bilateral orchiectomy along with palliative TURP in a single surgical act. With regard to the pathology reports, tumor tissue was found in 50 patients (76%), and no tumor was observed in the remaining 16 patients (24%). In one case (1.5%), the Gleason score (GS) could not be determined due to the effects of orchiectomy. Under-staging in the grade group was evidenced in 23 patients (46.9%), over-staging in three patients (6.3%), and no difference in 23 patients (46.9%), when compared to the initial GS at biopsy. The mortality rate and the incidence of TURP syndrome were low (3.1% and 1.5%, respectively). A 46% reduction in the mean serum prostate-specific antigen (PSA) value was documented when the preoperative and postoperative values were compared. Conclusion A decrease in the serum PSA levels was observed after palliative TURP, and despite having received ADT, it was possible to determine tumor pathology in the resected tissue, being able to identify a greater grade group compared the GS at the time of diagnosis. The palliative TURP proved to be a safe procedure to relieve LUTS in patients with advanced PCa, with a low morbidity and mortality rate.

Tamización poblacional para la detección temprana del cáncer de próstata: ¿Qué hemos aprendido en los últimos 10 años? / Population Screening for Early Detection of Prostate Cancer: ¿What have we Learned in the Last Decade?

Introducción Desde el inicio de la aplicación del cribado para cáncer de próstata basado en el antígeno prostático específico (PSA) hace aproximadamente dos décadas, la controversia sobre los beneficios y desventajas de su uso rutinario ha sido constante. La literatura médica cuenta con múltiples estudios que en ocasiones han revelado resultados contradictorios sobre los posibles beneficios de la tamización con PSA; la tasa de detección de cáncer de próstata indolente detectado parece ser alta y los estudios no demuestran de forma constante los beneficios en términos de reducción de la mortalidad cáncer específica o general. El propósito del presente artículo, es definir a la luz de la literatura médica reciente, la utilidad a nivel poblacional del cribado para cáncer de próstata basado en el antígeno prostático específico. Materiales y métodos Se realizó una revisión en los buscadores Pubmed, Embase y Lilacs utilizando los términos MesH "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination," "Outcome assesment (Health care)." Se filtró la búsqueda hacia estudios ejecutados en humanos, y/o metanálisis y revisiones sistemáticas publicados durante los últimos 10 años. Los abstracts fueron valorados por el grupo de autores e incluidos para análisis según su aporte al objetivo principal del estudio. Algunas referencias adicionales fueron añadidas dada su importancia clínica e histórica. Resultados Se identificaron 23 referencias con la estrategia de búsqueda, se excluyeron del análisis 9 referencias por no aportar datos relevantes para el presente artículo. Se incluyeron para revisión un total de 14 artículos. Discusión La tamización para cáncer de próstata con base en el antígeno específico de próstata sérico es una estrategia que permite aumentar la tasa de detección temprana de cáncer, sin embargo, se asocia a una importante tasa de detección de cáncer de próstata indolente y de sobretratamiento. Los resultados de la literatura evaluada son contradictorios con respecto al efecto que tiene la tamización sobre la mortalidad específica por cáncer, algunos estudios han revelado una disminución de ese ítem en los pacientes sometidos a tamización para cáncer de próstata. Los datos también son contundentes en demostrar que las estrategias de tamización no han impactado la supervivencia general en los grupos estudiados. Se esperan resultados de estudios que incluyan el armamento de estrategias disponibles para estimar el riesgo de cáncer de próstata (imágenes y/o nuevos marcadores tumorales) con el fin de mejorar la relación riesgo/beneficio de la estrategia de cribado para cáncer de próstata. Conclusiones La tamización para cáncer de próstata debe ser una estrategia para la detección temprana del cáncer que se usa de forma consensuada con cada paciente y que debe adaptarse al riesgo individual; el paciente a quien se le aplica el cribado debe entender los potenciales riesgos y beneficios de esta estrategia ya que los datos disponibles no permiten demostrar con alto nivel de evidencia, un beneficio clínico traducido en términos de reducción en la mortalidad del cáncer específica o general.

Introduction In the last decade, the prostate-specific antigen based screening for prostate cancer have evoque a lot of controversies on the basis of his risk ­ benefit ratio; there are controversial data about the impact of this strategy in the male cancer specific and general mortality. The aim of this article is to show the most recent findings and to define the utility of the population screening for early detection of prostate cancer. Material and Methods A literature review was performed in PubMed, Embase and Lilacs using the MeSH terms: "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination" and "Outcome assesment (Health care)" which was limited to scientific articles published in the past 10 years. The abstracts were evaluated and excluded if they were not related to primary aim of this article. Some references were included given their clinical relevance. Results 23 articles were retrieved, and after reviewing the abstracts, 9 articles were excluded as they were not related to our primary aim. The analysis was performed in 14 articles. Discussion The prostate-specific antigen based population screening has been associated with an early diagnosis of prostate cancer even, in a non significative clinical stage, and consequent overtreatment. The literature which was evaluated have controvesial outcomes on the cancer-specific mortality, however none of the articles evaluated shown a significant impact in male general mortality. In the overcoming years, we expect the results of some investigations which includes additional tools for the screening of prostate cancer (multiparametric prostate resonance imaging, new tumoral markers), to improve the risk-benefit of this strategy. Conclusions The population prostate cancer screening should be made in well-informed patients and shared based decision process. The urologist and patient should to know the potential benefits and risks of this strategy, because there is not high grade level of evidence which supports a significant effect of this strategy in male general and cancer-specific mortality.

Complicaciones de las derivaciones urinarias heterópicas no continentes: Ureterostomías cutáneas vs conducto ileal / Complications of Non-continent Heteropic Urinary Derivations: Skin Ureterostomies vs Ileal Duct

Introducción Y Objetivos Las derivaciones del tracto urinario abarcan una amplia gama de técnicas quirúrgicas, siendo la causa más frecuente para su uso la patología urotelial maligna. De las derivaciones urinarias no continentes heterótopicas las más utilizadas son el conducto ileal y las ureterostomias cutáneas. La elección de la técnica dependerá de la patología de base, las condiciones del paciente y la experiencia del cirujano. El objetivo de este trabajo es determinar las complicaciones tempranas (≤30 días) y tardías (>30 días) de derivaciones urinarias heterópicas no continentes (DUHNC) tipo conducto ileal (CI) vs ureterostomias cutáneas (UC). Métodos Se realizó un estudio descriptivo retrospectivo de los pacientes llevados a DUHNC tipo CI o UC, desde enero del 2008 a julio del 2016, en un centro de referencia para patología oncológica. Se evaluó: edad, género, comorbilidades, escala de Karnofsky, patología quirúrgica, sangrado, ASA, tiempo quirúrgico, estancia hospitalaria, complicaciones tempranas y tardías. Resultados De los 70 pacientes incluidos, 26 con UC y 44 con CI, prevaleciendo el género masculino en ambos grupos. El promedio de edad fue de 66 y 63 años respectivamente y el indice Karnofsky en todos los pacientes fue superior al 90%. La causa más frecuente fue patología maligna de vejiga. El tiempo quirúrgico fue mayor en los pacientes del CI, siendo estadísticamente significativo (p = 0.000). El sangrado fue similar en ambas técnicas quirúrgicas requiriendo transfusión de hemoderivados el 92,3% de los pacientes con UC y 88,6% de los CI. La estancia hospitalaria no tuvo diferencias. En cuanto a las complicaciones tempranas, la más frecuente en ambos grupos fue el choque hipovolémico (61% UC y 58% CI). De las complicaciones tardías la sepsis urinaria prevaleció en ambos grupos (34% y 18% respectivamente) y la estrechez del estoma y la anastomosis ureteroileal se presentaron en las UC y en los CI respectivamente. La mortalidad en el transoperatorio fue del 12,8%. Conclusiones Las DUHNC como las ureterostomias cutáneas o el conducto ileal son técnicas quirúrgicas con tasas de sangrado, transfusión y estancia hospitalaria similares, pero con una menor proporción de complicaciones tanto tempranas como tardías en los pacientes llevados a conducto ileal

Introduction and Objectives The derivations of the urinary tract cover a wide range of surgical techniques, being the most frequent cause for its use the malignant urothelial pathology. Of the urinary diversions, the heterotopic continents are the ileal conduit and the cutaneous ureterostomies. The choice of technique will depend on the underlying pathology, the patient's conditions and the experience of the surgeon. The aim of this study is to determine the early complications (≤30 days) and late complications (> 30 days) of noncontinental heteropic urinary diversions (NHUD) type ileal conduit (IC) vs cutaneous ureterostomies (CU). Methods A retrospective descriptive study was conducted of patients referred to NHUD type CI or CU, from January 2008 to July 2016, in a referral center for oncological pathology. We evaluated: age, gender, comorbidities, Karnofsky scale, surgical pathology, bleeding, ASA, surgical time, hospital stay, early and late complications. Results Of the 70 patients included, 26 with CU and 44 with IC, the male gender prevailing in both groups. The average age was 66 and 63 years respectively and the Karnofsky index in all patients was over 90%. The most frequent cause was malignant pathology of the bladder. Surgical time was higher in IC patients, being statistically significant (p = 0.000). Bleeding was similar in both surgical techniques requiring transfusion of blood products 92.3% of patients with CU and 88.6% of IC. The hospital stay did not differ. Regarding the early complications, the most frequent in both groups was hypovolemic shock (61% CU and 58% CI). Of the late complications, urinary sepsis prevailed in both groups (34% and 18% respectively) and the narrowing of the stoma and the ureteroileal anastomosis were present in the CU and in the IC, respectively. The mortality in the transoperative period was 12.8%. Conclusions NHUD such as cutaneous ureterostomies or ileal conduit are surgical techniques with similar rates of bleeding, transfusion and hospital stay, but with a lower proportion of complications both early and late in patients taken to the ileal conduit.