Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

Fístula arterioileal: experiencia en un hospital terciario y revisión de la literatura / Arterial-ileal fistula: experience from a tertiary referral center and literature review

Introducción y objetivo: la fístula entre la arteria ilíaca y el conducto ileal (Bricker) es una patología con un elevado riesgo vital. El objetivo de este artículo es dar a conocer esta entidad, describir su presentación, sus métodos diagnósticos y su tratamiento basados en los casos en un hospital terciario y en la revisión de la literatura. Material y métodos: presentamos los casos de fístulas arterioileales ocurridos en nuestro centro entre 2016 y 2020. Se realizó una exhaustiva revisión de la literatura publicada hasta la fecha mediante la búsqueda en PubMed de artículos publicados entre 1971 y 2020, incluyendo las palabras claves “arterial ileal conduit fistula” y seleccionando únicamente los artículos en español e inglés. Resultados: se identificaron 4 casos en nuestro centro. Se reconocieron en la búsqueda bibliográfica 13 artículos que describían 16 casos de fístulas arterioileales. La mayoría compartía factores comunes de riesgo y el abordaje quirúrgico fue mayoritariamente la cirugía abierta. El abordaje adecuado parece ser la combinación de cirugía abierta y endovascular, efectiva en 3 de nuestros 4 casos. Conclusión: la fístula entre la arteria ilíaca y el conducto ileal es una complicación infrecuente y grave, con una mortalidad en torno al 44 %. Resulta difícil de diagnosticar, salvo que exista alta sospecha clínica, con pocos casos descritos en la literatura. Es fundamental tener en cuenta la historia clínica previa del paciente. (AU)

Introduction and objective: the presence of a fistula between the iliac artery and the ileal conduit is a live-threatening condition that must be known and, therefore, suspected after a massive bleeding through the ileal conduit. The objective of this article is to present the arterial-ileal fistula, describe its presentation, diagnostic methods, and treatments, based on the cases presented in a tertiary referral center and literature review. Material and methods: all cases of arterial-ileal fistulas collected at our center from 2016 through 2020 are presented here. A comprehensive literature review published to date was also conducted based on a search for articles published from 1971 through 2020 on the PubMed database with the keywords “arterial ileal conduit fistula”, including studies only published in English and Spanish languages. Results: a total of 4 cases were identified in our center. A total of 13 articles describing 16 cases of arterial-ileal fistula were identified from the medical literature, most of them with some risk factors in common. The approach followed was mainly open surgery. The proper treatment seems to be a combination between open surgery and endovascular approaches, which turned out to be effective in 3 of our 4 cases. Conclusion: a fistula between the artery and the ileal conduit is a rare but serious complication, with a 44% mortality rate. It is difficult to diagnose unless there is clinical suspicion involved, with only a few cases reported in the medical literature. We should consider the patient’s pathological history to identify this entity. (AU)

Reducing the demand for magnetic resonance imaging scans and prostate biopsies during the early detection of clinically significant prostate cancer: Applying the Barcelona risk-stratified pathway in Catalonia.

PURPOSE: To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia. MATERIALS AND METHODS: A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2. RESULTS: CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%. CONCLUSION: The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.

Investigating Efficient Risk-Stratified Pathways for the Early Detection of Clinically Significant Prostate Cancer.

Risk-stratified pathways (RSPs) are recommended by the European Association of Uro-logy (EAU) to improve the early detection of clinically significant prostate cancer (csPCa). RSPs can reduce magnetic resonance imaging (MRI) demand, prostate biopsies, and the over-detection of insignificant PCa (iPCa). Our goal is to analyze the efficacy and cost-effectiveness of several RSPs by using sequential stratifications from the serum prostate-specific antigen level and digital rectal examination, the Barcelona risk calculators (BCN-RCs), MRI, and Proclarix™. In a cohort of 567 men with a serum PSA level above 3.0 ng/mL who underwent multiparametric MRI (mpMRI) and targeted and/or systematic biopsies, the risk of csPCa was retrospectively assessed using Proclarix™ and BCN-RCs 1 and 2. Six RSPs were compared with those recommended by the EAU that, stratifying men from MRI, avoided 16.7% of prostate biopsies with a prostate imaging-reporting and data system score of <3, with 2.6% of csPCa cases remaining undetected. The most effective RSP avoided mpMRI exams in men with a serum PSA level of >10 ng/mL and suspicious DRE, following stratifications from BCN-RC 1, mpMRI, and Proclarix™. The demand for mpMRI decreased by 19.9%, prostate biopsies by 19.8%, and over-detection of iPCa by 22.7%, while 2.6% of csPCa remained undetected as in the recommended RSP. Cost-effectiveness remained when the Proclarix™ price was assumed to be below EUR 200.

Testicular fibroma of gonadal stromal origin in an adult male / Fibroma testicular de origen gonadal estromal en un varón adulto

Para-testicular masses are a rare entity, and therefore the diagnosis and management nearly always lead to clinical doubts. Aside from the doubts that arise from these masses being uncommon, it is always necessary to rule out the malignancy process of them. Sexual cord tumors are extremely rare. Testicular fibroma of gonadal stromal origin is a proliferative process that can develop in para-testicular structures. The objective of our study is to present a rare case report of testicular fibroma of gonadal stromal origin as well as the well-documented diagnostic process and the successful therapeutic management that was subsequently carried out. We report a case of a 68-year old male who came in for a consult due to the casual finding of a nodule in his left testicle with normal tumor markers. Ultrasonography showed a nodular image that was well-defined with a diffusely homogeneous echotexture; it was also hypoechoic, vascularized and demonstrated hydrocele. MRI revealed a solid tumor with extrinsic growth to the left testicle and epididymis, and the lesion was relatively hyperintense in T1-weighted image and hypointense in T2. A surgical exeresis of the para-testicular tumor and hydrocelectomy was performed. The pathological anatomy and immunohistochemistry revealed a fibroma of gonadal stromal origin. Histopathological analysis made a diagnosis, although its clinical and radiological characteristics make it one of the differential diagnoses to consider in testicular tumors. Its characteristics, radiological and histopathological, allow for conservative management in clinical practice. (AU)

Las masas paratesticulares son una entidad rara, por lo que su diagnóstico y tratamiento casi siempre dan lugar a dudas clínicas. Más allá de las dudas que surgen por el hecho de que estas masas sean poco comunes, siempre hay que descartar el proceso de malignidad de las mismas. Los tumores del cordón sexual son extremadamente raros. El fibroma testicular de origen estromal gonadal es un proceso proliferativo que puede desarrollarse en estructuras paratesticulares. El objetivo de nuestro estudio es presentar un reporte de un caso raro de fibroma testicular de origen del estroma gonadal así como el proceso diagnóstico bien documentado y el manejo terapéutico exitoso que se llevó a cabo posteriormente. Presentamos el caso de un varón de 68 años que acude a consulta por el hallazgo casual de un nódulo en el testículo izquierdo con marcadores tumorales normales. La ecografía mostró una imagen nodular bien definida con una ecotextura difusamente homogénea; además era hipoecoico, vascularizado y demostraba hidrocele. La resonancia magnética reveló un tumor sólido con crecimiento extrínseco en el testículo izquierdo y el epidídimo, y la lesión era relativamente hiperintensa en la imagen potenciada en T1 e hipointensa en T2. Se realizó exéresis quirúrgica del tumor paratesticular e hidrocelectomía. La anatomía patológica y la inmunohistoquímica revelaron un fibroma de origen estromal gonadal. El análisis histopatológico permitió establecer el diagnóstico, aunque sus características clínicas y radiológicas lo convierten en uno de los diagnósticos diferenciales a considerar en los tumores testiculares. Sus características, radiológicas e histopatológicas, permiten un manejo conservador en la práctica clínica. (AU)

Comparison of Rotterdam and Barcelona Magnetic Resonance Imaging Risk Calculators for Predicting Clinically Significant Prostate Cancer.

Background: Magnetic resonance imaging (MRI)-based risk calculators (MRI-RCs) individualise the likelihood of clinically significant prostate cancer (csPCa) and improve candidate selection for prostate biopsy beyond the Prostate Imaging Reporting and Data System (PI-RADS). Objective: To compare the Barcelona (BCN) and Rotterdam (ROT) MRI-RCs in an entire population and according to the PI-RADS categories. Design setting and participants: A prospective comparison of BCN- and ROT-RC in 946 men with suspected prostate cancer in whom systematic biopsy was performed, as well as target biopsies of PI-RADS ≥3 lesions. Outcome measurements and statistical analysis: Saved biopsies and undetected csPCa (grade group ≥2) were determined. Results and limitations: The csPCa detection was 40.8%. The median risks of csPCa from BCN- and ROT-RC were, respectively, 67.1% and 25% in men with csPCa, whereas 10.5% and 3% in those without csPCa (p < 0.001). The areas under the curve were 0.856 and 0.844, respectively (p = 0.116). BCN-RC showed a higher net benefit and clinical utility over ROT-RC. Using appropriate thresholds, respectively, 75% and 80% of biopsies were needed to identify 50% of csPCa detected in men with PI-RADS <3, whereas 35% and 21% of biopsies were saved, missing 10% of csPCa detected in men with PI-RADS 3. BCN-RC saved 15% of biopsies, missing 2% of csPCa in men with PI-RADS 4, whereas ROT-RC saved 10%, missing 6%. No RC saved biopsies without missing csPCa in men with PI-RADS 5. Conclusions: ROT-RC provided a lower and narrower range of csPCa probabilities than BCN-RC. BCN-RC showed a net benefit over ROT-RC in the entire population. However, BCN-RC was useful in men with PI-RADS 3 and 4, whereas ROT-RC was useful only in those with PI-RADS 3. No RC seemed to be helpful in men with negative MRI and PI-RADS 5. Patient summary: Barcelona risk calculator was more helpful than Rotterdam risk calculator to select candidates for prostate biopsy.

A multistate model and its standalone tool to predict hospital and ICU occupancy by patients with COVID-19.

Objective: This study aims to build a multistate model and describe a predictive tool for estimating the daily number of intensive care unit (ICU) and hospital beds occupied by patients with coronavirus 2019 disease (COVID-19). Material and methods: The estimation is based on the simulation of patient trajectories using a multistate model where the transition probabilities between states are estimated via competing risks and cure models. The input to the tool includes the dates of COVID-19 diagnosis, admission to hospital, admission to ICU, discharge from ICU and discharge from hospital or death of positive cases from a selected initial date to the current moment. Our tool is validated using 98,496 cases positive for severe acute respiratory coronavirus 2 extracted from the Aragón Healthcare Records Database from July 1, 2020 to February 28, 2021. Results: The tool demonstrates good performance for the 7- and 14-days forecasts using the actual positive cases, and shows good accuracy among three scenarios corresponding to different stages of the pandemic: 1) up-scenario, 2) peak-scenario and 3) down-scenario. Long term predictions (two months) also show good accuracy, while those using Holt-Winters positive case estimates revealed acceptable accuracy to day 14 onwards, with relative errors of 8.8%. Discussion: In the era of the COVID-19 pandemic, hospitals must evolve in a dynamic way. Our prediction tool is designed to predict hospital occupancy to improve healthcare resource management without information about clinical history of patients. Conclusions: Our easy-to-use and freely accessible tool (https://github.com/peterman65) shows good performance and accuracy for forecasting the daily number of hospital and ICU beds required for patients with COVID-19.

Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer.

INTRODUCTION: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model.

PURPOSE: To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT). MATERIALS AND METHODS: A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.5 and 3.5 ng/mL, respectively. The cumulative incidence curve described the recovery of testosterone. Univariate and multivariate analyzes were performed to predict testosterone recovery with candidate prognostic factors prostate-specific antigen at diagnosis, clinical stage, Gleason score from biopsy, age at cessation of ADT, duration of ADT, primary therapy and use of LHRH (luteinizing hormone-releasing hormone) agonists. RESULTS: The median follow-up duration in the study was 80 months (interquartile range, 49-99 mo). Twenty-five percent and 81% of patients did not recover the castrate and normogonadic levels, respectively. Duration of ADT and age at ADT cessation were significant predictors of testosterone recovery. We built two nomograms for testosterone recovery at 12, 24, 36, and 60 months. The castration recovery model had good calibration. The C-index was 0.677, with area under the receiver operating characteristic curve (AUC-ROC) of 0.736, 0.783, 0.782, and 0.780 at 12, 24, 36, and 60 months, respectively. The normogonadic recovery model overestimated the higher values of probability of recovery. The Cindex was 0.683, with AUC values of 0.812, 0.711, 0.708 and 0.693 at 12, 24, 36, and 60 months, respectively. CONCLUSIONS: Depending on the age of the patient and the length of treatment, clinicians may stop ADT and the castrated testosterone level will be maintained or, if the course of treatment has been short, we can estimate if it will return to normogonadic levels.

A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand.

A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016−31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800−0.846) in the development cohort and 0.837 (95% CI: 0.811−0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22−0.26) in the development cohort and 0.34 (95% CI: 0.31−0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa.

Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy.

This study is a head-to-head comparison between mPSAD and MRI-PMbdex. The MRI-PMbdex was created from 2432 men with suspected PCa; this cohort comprised the development and external validation cohorts of the Barcelona MRI predictive model. Pre-biopsy 3-Tesla multiparametric MRI (mpMRI) and 2 to 4-core transrectal ultrasound (TRUS)-guided biopsies for suspicious lesions and/or 12-core TRUS systematic biopsies were scheduled. Clinically significant PCa (csPCa), defined as Gleason-based Grade Group 2 or higher, was detected in 934 men (38.4%). The area under the curve was 0.893 (95% confidence interval [CI]: 0.880−0.906) for MRI-PMbdex and 0.764 (95% CI: 0.774−0.783) for mPSAD, with p < 0.001. MRI-PMbdex showed net benefit over biopsy in all men when the probability of csPCa was greater than 2%, while mPSAD did the same when the probability of csPCa was greater than 18%. Thresholds of 13.5% for MRI-PMbdex and 0.628 ng/mL2 for mPSAD had 95% sensitivity for csPCa and presented 51.1% specificity for MRI-PMbdex and 19.6% specificity for mPSAD, with p < 0.001. MRI-PMbdex exhibited net benefit over mPSAD in men with prostate imaging report and data system (PI-RADS) <4, while neither exhibited any benefit in men with PI-RADS 5. Hence, we can conclude that MRI-PMbdex is more accurate than mPSAD for the proper selection of candidates for prostate biopsy among men with suspected PCa, with the exception of men with a PI-RAD S 5 score, for whom neither tool exhibited clinical guidance to determine the need for biopsy.

[Lymphoepithelioma-like bladder tumor. A rare variant.] / Tumor vesical linfoepitelioma-like. Una variante infrecuente.

INTRODUCTION: Lymphoepitheliomalikedifferentiation is a rare histological variant of urothelialbladder carcinoma, therefore its prognosis and treatmentare not clearly defined. A retrospective study of 5cases in the last 10 years in our center was performed. CASE REPORT: cystectomy was performed in 4 of5 because they were non-metastatic muscle-invasivetumors at diagnosis, in the 5th TURB + BCG because itwas non-muscle-invasive. 2 patients received chemotherapyand 1 adjuvant radiotherapy, and 1 immunotherapyafter relapse. 2 had a pure lymphoepithelioma-like pattern, 2 predominant and 1 focal. DISCUSSION: In predominant or pure forms, agood response to treatment with TURB and adjuvantchemotherapy has been described, even superior tocystectomy, as it is a variant with a very favorable responseto platinum. Immunotherapy is currently onlyindicated as second-line treatment. CONCLUSIONS: adjuvant treatment plays an importantrole as it is a highly chemosensitive variant, but more studies are needed to define the best therapeuticstrategy.

INTRODUCCIÓN: La diferenciaciónlinfoepitelioma-like es una variante histológica pocofrecuente del carcinoma urotelial vesical, por lo que supronóstico y tratamiento no está claramente definido.Se presenta un estudio retrospectivo de 5 casos en losúltimos 10 años en nuestro centro.DESCRIPCIÓN DE CASOS: en 4 de los casos se realizócistectomía por ser tumores músculo-invasivosno metastásicos al diagnóstico, en el 5º RTU + BCGpor ser no músculo-invasivo. 2 pacientes recibieronquimioterapia y 1 radioterapia en adyuvancia, y 1 inmunoterapiatras recidiva. 2 presentaban un patrónlinfoepitelioma-like puro, 2 predominante y 1 focal.DISCUSIÓN: en formas predominantes o puras seha descrito buena respuesta al tratamiento con RTU yquimioterapia adyuvante, incluso superiores a cistectomía,por ser una variante con respuesta muy favorableal platino. La inmunoterapia actualmente solo estáindicada como tratamiento en segunda línea. CONCLUSIONES: el tratamiento adyuvante tiene unpapel importante por ser una variante muy quimiosensible,pero son necesarios más estudios para definirla mejor estrategia terapéutica.

Multiparametric Magnetic Resonance Imaging Grades the Aggressiveness of Prostate Cancer.

We sought to find further evidence showing the increase in PCa aggressiveness as PI-RADS score increases from four surrogates of PCa aggressiveness: i. prostate biopsy GG (≤3 vs. >3), ii. type of pathology in surgical specimens (favourable vs. unfavourable), iii. clinical stage (localised vs. advanced), and risk of recurrence of localised PCa after primary treatment (low-intermediate vs. high). A group of 692 PCa patients were diagnosed after 3-T multiparametric MRI (mpMRI) and guided and/or systematic biopsies, showing csPCa (GG ≥ 2) in 547 patients (79%) and insignificant PCa (iPCa) in 145 (21%). The csPCa rate increased from 32.4% in PI-RADS < 3 to 95.5% in PI-RADS 5 (p < 0.001). GG ≥ 3 was observed in 7.6% of PCa with PI-RADS < 3 and 32.6% in those with PI-RADS > 3 (p < 0.001). Unfavourable pathology was observed in 38.9% of PCa with PI-RAD < 3 and 68.3% in those with PI-RADS > 3 (p = 0.030). Advanced disease was not observed in PCa with PI-RADS ≤ 3, while it existed in 12.7% of those with PI-RADS > 3 (p < 0.001). High-risk recurrence localised PCa was observed in 9.5% of PCa with PI-RADS < 3 and 35% in those with PI-RADS > 3 (p = 0.001). The PI-RADS score was an independent predictor of all surrogates of PCa aggressiveness as PSA density. We confirmed that mpMRI grades PCa aggressiveness.

Tumor vesical linfoepitelioma-like. Una variante infrecuente / Lymphoepithelioma-like bladder tumor. A rare variant

INTRODUCCIÓN: La diferenciaciónlinfoepitelioma-like es una variante histológica pocofrecuente del carcinoma urotelial vesical, por lo que supronóstico y tratamiento no está claramente definido.Se presenta un estudio retrospectivo de 5 casos en losúltimos 10 años en nuestro centro.DESCRIPCIÓN DE CASOS: en 4 de los casos se realizó cistectomía por ser tumores músculo-invasivosno metastásicos al diagnóstico, en el 5º RTU + BCGpor ser no músculo-invasivo. 2 pacientes recibieronquimioterapia y 1 radioterapia en adyuvancia, y 1 inmunoterapia tras recidiva. 2 presentaban un patrónlinfoepitelioma-like puro, 2 predominante y 1 focal.DISCUSIÓN: en formas predominantes o puras seha descrito buena respuesta al tratamiento con RTU yquimioterapia adyuvante, incluso superiores a cistectomía, por ser una variante con respuesta muy favorable al platino. La inmunoterapia actualmente solo estáindicada como tratamiento en segunda línea. CONCLUSIONES: el tratamiento adyuvante tiene unpapel importante por ser una variante muy quimiosensible, pero son necesarios más estudios para definir la mejor estrategia terapéutica.(AU)

INTRODUCTION: Lymphoepitheliomalike differentiation is a rare histological variant of urothelial bladder carcinoma, therefore its prognosis and treatment are not clearly defined. A retrospective study of 5cases in the last 10 years in our center was performed.CASE REPORT: cystectomy was performed in 4 of5 because they were non-metastatic muscle-invasivetumors at diagnosis, in the 5th TURB + BCG because itwas non-muscle-invasive. 2 patients received chemotherapy and 1 adjuvant radiotherapy, and 1 immunotherapy after relapse. 2 had a pure lymphoepithelioma-like pattern, 2 predominant and 1 focal.DISCUSSION: In predominant or pure forms, agood response to treatment with TURB and adjuvantchemotherapy has been described, even superior tocystectomy, as it is a variant with a very favorable response to platinum. Immunotherapy is currently onlyindicated as second-line treatment.CONCLUSIONS: adjuvant treatment plays an important role as it is a highly chemosensitive variant, but more studies are needed to define the best therapeutic strategy. (AU)

The Barcelona Predictive Model of Clinically Significant Prostate Cancer.

A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories.

[Tumor markers in urological cancers: an update.] / Actualización en biomarcadores tumorales en urología.

La investigación en biomarcadores tumorales estásujeta a unas estrictas normas para su comercialización.Pese a ello, en su uso abierto a distintas poblaciones,somos sometidos a una presión comercialque en ocasiones puede derivar inconscientemente aextender su uso a objetivos para los que no han sidoestrictamente testados...

La investigación en biomarcadores tumorales estásujeta a unas estrictas normas para su comercialización.Pese a ello, en su uso abierto a distintas poblaciones,somos sometidos a una presión comercialque en ocasiones puede derivar inconscientemente aextender su uso a objetivos para los que no han sidoestrictamente testados...

Statistical characterization of a good biomarker in oncology. / Características bioestadísticas de un buen biomarcador en Oncología.

OBJECTIVE: The  aim of this article is to review and illustrate the attributes that analyze the performance of a predictive model, suchas discrimination, calibration and clinical utility. MATERIAL AND METHODS: To illustrate a biomarkervalidation process, we analyzed 216 patientsrecruited in the Miguel Servet University Hospital Zaragoza, Spain. The outcome of the study was clinicallysignificant prostate cancer (Gleason ≥ 7). A newbiomarker was built using logistic regression modelfrom age, prostate-specific antigen, prostate volumeand digital rectal exam variables. To analyze the discriminationability, the receiver operating characteristiccurve, its area under the curve (AUC), and Youdenindex were estimated. In addition, the calibration wasanalyzed through calibration curve, intercept and slope;and the clinical utility was studied by means of decisionand clinical utility curves. RESULTS: The discrimination ability was good:AUC 0.790 (0.127-0.853 95% C.I.), Youden index cutoffpoint 0.431 (specificity 0.811, sensitivity 0.697).The Intercept was 0 and Slope 1 showing a perfect calibration.Decision curve showed good net benefit in athreshold probability range 25%-80%. Clinical utilitycurve showed that for a 18% cutoff point, a minimum4.5% of CsPCa patients are wrongly classified belowthe cutoff point, saving 18.5% biopsies. CONCLUSIONS: A complete validation process isnecessary to analyze the performance of a biomarkerin oncology, based on their discrimination ability, theconcordance between predicted and actual occurrenceof the outcome, and its applicability in clinical practice.

OBJETIVO: El objetivo principal de esteartículo es revisar e ilustrar las propiedades para analizarel desempeño de un modelo predictivo, que sonla discriminación, calibración y utilidad clínica.MATERIAL Y MÉTODOS: Para ilustrar un procesode validación de biomarcadores, analizamos 216 pacientesreclutados en el Hospital Universitario MiguelServet, Zaragoza, España. El objetivo a predecir en elestudio fue un cáncer de próstata clínicamente significativo(Gleason ≥ 7). Se construyó un nuevo biomarcadorutilizando un modelo de regresión logísticausando la edad, el antígeno prostático específico, elvolumen de la próstata y el tacto rectal como variablespredictoras. Para analizar la capacidad de discriminaciónse estimó la curva característica de funcionamientodel receptor, su área bajo la curva (AUC) y elíndice de Youden. Además, la calibración se analizómediante curva de calibración, intersección y pendiente;y la utilidad clínica se estudió mediante curvasde decisión y utilidad clínica. RESULTADOS: La capacidad de discriminación fuebuena: AUC 0,790 (0,127-0,853 IC del 95%), punto decorte del índice de Youden 0,431 (especificidad 0,811,sensibilidad 0,697). La intersección fue 0 y la pendiente1, mostrando una calibración perfecta. La curva dedecisión muestra un buen beneficio neto en un rangode probabilidad del 25% al 80%. La curva de utilidadclínica mostró que para un punto de corte del 18%, seproduce un mínimo del 4,5% de los pacientes con CsPCaclasificados incorrectamente por debajo del puntode corte, ahorrando un 18,5% de biopsias. CONCLUSIONES: Es necesario un proceso de validacióncompleto para analizar el desempeño de un biomarcadoren oncología, en función de su capacidad dediscriminación, la concordancia entre las prediccionesque proporciona el marcador y la ocurrencia real delevento, y su aplicabilidad en la práctica clínica.