External validation of the barcelona magnetic resonance imaging predictive model for detecting significant prostate cancer including men receiving 5-alpha reductase inhibitors.

PURPOSE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). MATERIALS AND METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.

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.

Active Surveillance in Prostate Cancer: Role of Available Biomarkers in Daily Practice.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients.

Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

How to implement magnetic resonance imaging before prostate biopsy in clinical practice: nomograms for saving biopsies.

PURPOSE: To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). METHODS: A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. RESULTS: Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing < 18% as the cutoff of probability for not performing PBx; the percentage of saved PBx was 47% (474 avoided PBx in 1000 proposed). CONCLUSION: We developed clinical and mpMRI-based nomograms with a high discrimination ability for three different scenarios of PCa aggressiveness (https://urostatisticalsolutions.shinyapps.io/MRIfusionPCPrediction/). Specific clinical cutoff points allow us to save a high number of PBx with a minimum of missed diagnoses.

Clinical and Surgical Assistance in Prostate Cancer during the COVID-19 Pandemic: Implementation of assistance protocols.

PURPOSE: Propose an approach of prostate cancer (PCa) patients during COVID-19 pandemic. MATERIAL AND METHODS: We conducted a review of current literature related to surgical and clinical management of patients during COVID-19 crisis paying special attention to oncological ones and especially those suffering from PCa. Based on these publications and current urological guidelines, a manual to manage PCa patients is suggested. RESULTS: Patients suffering from cancer are likely to develop serious complications from COVID-19 disease together with an increased risk of postoperative morbidity and mortality. Therefore, the management of oncological patients should be taken into special consideration and most of the treatments postponed. In case the procedure is not deferrable, it should be adapted to the current situation. While the shortest radiotherapy (RT) regimens should be applied, surgical procedures must undergo the following recommendations proposed by main surgical associations. PCa prognosis is generally favourable and therefore one can safely delay most of the biopsies up to 6 months without interfering with survival outcomes in the vast majority of cases. In the same way, most of the localised PCa patients are suitable for active surveillance (AS) or hormonal therapy until local definitive treatment could be reconsidered. In metastatic as well as castration resistant PCa stages, adding androgen receptor targeted agents (abiraterone, apalutamide, darolutamide or enzalutamide) to androgen-deprivation therapy (ADT) could be considered in high risk patients. On the contrary, chemotherapy, immunotherapy and Radium-223 must be avoided with regard to the consequence of hematologic toxicity and risk of COVID-19 infection because of immunodepression. CONCLUSIONS: Most of the biopsies should be delayed while AS is advised in those patients with low risk PCa. ADT allows us to defer definitive local treatment in many cases of intermediate and high risk PCa. In regard to metastatic and castration resistant PCa, combination therapies with abiraterone, apalutamide, darolutamide or enzalutamide could be considered. Chemotherapy, Radium-223 and immunotherapy are discouraged.

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.

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%.

[Patient with testosterone deficit syndrome after external beam radiotherapy]. / Paciente con síndrome de déficit de testosterona tras radioterapia externa.

Testosterone deficit syndrome is a clinical and biochemical syndrome associated with advanced age and characterized by some symptomsassociated with serum testosterone levels deficiency, which may result in a decrease of quality of life and negatively affect the function of multiple organs or systems. Clinical guidelines recommend testosterone replacement therapy (TRT) in patients with testosterone decrease that associate muscle mass and strength loss, lumbar spinal column bone density decrease, or libido and erection decrease. Contraindications for treatment would include active prostate cancer or without treatment, PSA >4 ng/ml waiting for diagnostic workup, breast cancer, severe sleep apnea, infertility, hematocrit over 50% or severe lower urinary tract symptoms secondary to benign prostatic hypertrophy. In certain situations there is still great controversy, without enough evidence to establish an action. References in case of patientstreated with brachytherapy or radiotherapy are unspecific: they only recommend caution in the treatment with TRT in these patients and strict monitoring of the possible recurrence. In our opinion, low-intermediate risk prostate cancer patients treated with radiotherapy only, without evidence of residual or recurrent disease, are candidates for TRT if symptoms justify it, leaving a free period of never less than one year after nadir (or 24 months after the end of therapy) which guarantees, on the possible means, the absence of biochemical or clinical recurrence,with strict follow up of clinical and biochemical usual parameters (hematocrit, hemoglobin, DRE, PSA).

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.

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.

[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...

[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.

Multidisciplinary Consensus on the Prevention and Treatment of Osteoporosis and Fragility Fractures in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy.

Patients with prostate cancer (PCa) on androgen-deprivation therapy (ADT) are at high risk of osteoporosis and fragility fractures. We aimed to provide some practical insights into the delivery of optimal bone health care for PCa patients, particularly those on ADT. An interdisciplinary group of experts, including urologists and rheumatologists developed recommendations based on their expertise, current evidence and guidelines. The multidisciplinary group's main recommendations are: fragility fracture risk should be assessed in all PCa patient, especially, in those under ADT. FRAX® tool may be incorporated into clinical practice to identify patients at high risk of fracture. Bone mineral density (BMD) should be measured routinely by dual energy X-ray absorptiometry in all patients scheduled for or on ADT. Thoracic and lumbar spine X-ray may be performed at the initial evaluation of patients with the diagnosis of osteoporosis and in case of suspected clinical vertebral fracture. Basic laboratory tests are recommended to exclude secondary osteoporosis. Treatment with bisphosphonates or denosumab should be considered in patients on ADT with fragility fracture, osteoporosis (BMD T-score ≤-2.5), or high risk of fracture according to FRAX®. Referral to a bone metabolism specialist should be contemplated in some cases. The recommendations provided in this document, tailored for clinicians treating PCa patients, may be of help to identify and treat patients at high risk of fracture.

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.

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.

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.

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.