Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial / 医学前沿

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer / 亚洲男科学杂志(英文版)

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard / 亚洲男科学杂志(英文版)

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Liquid chromatography-mass spectrometry for simultaneous determination of spironolactone and canrenone in plasma samples

Abstract n our study, we aimed to validate a method based on liquid chromatography-mass spectrometry (LC-MS) to quantify spironolactone (SPI) and its active metabolite canrenone (CAN) simultaneously in plasma samples to support in vivo experiments. Compounds were separated by using a C18 column with the isocratic elution of a mobile phase composed of 0.1% (v/v) formic acid in methanol-water (60:40 v/v) at a flow rate of 0.4 mL min−1. SPI and CAN were detected in na electrospray interface operating in a positive ionization mode and quantified using the selective ion mode monitoring of mass-charge ratios (m/z) of 439.0 for SPI and 363.1 for CAN. After calculating the matrix effect using theoretical equations, we observed the strong interference of plasma in the equipment-generated signal, which required creating analytical curves using the matrix as a solvent. The method was nevertheless linear (r 2 > 0.999) in a concentration range of 0.4-5.0 µg mL−1, as well as precise, with a coefficient of variation less than 5%. SPI's and CAN's recovery rates from the plasma ranged from 87.4% to 112.1%, while their limits of detection (i.e., 0.07 µg mL−1 and 0.03 µg mL−1, respectively) and quantification (i.e., 0.20 µg mL−1 and 0.08 µg mL−1, respectively) in the presence of plasma contaminants were low. Therefore, the bioanalytical method seems to be feasible for quantifying SPI and CAN in plasma

Tratamiento hormonal de la pedofilia: ¿puede curar la pedofilia con la castración química? / Pedophilia hormonal therapy: can pedophilia be cured with chemical castration

Históricamente la sociedad ha rechazado el abuso sexual de menores de 13 años, dictándose leyes al respecto. La justicia luego de un debido proceso condenaba al victimario con reclusión incluso hasta la década del 70-80, con orquiectomía. Los adelantos en neurobiología, endocrinología, sicofarmacología y sicología se consideraron las bases para tratar al pedófilo y someterlo a libertad condicional, ahorrándose el costo financiero de la reclusión de por vida. Diversos países dictaron leyes contra la conducta pedófila. En dicha legislación ejerció gran influencia la promulgación en EE.UU. (estado de Washington "sobre el ofensor sexual" y el dictamen de la Corte Suprema en 1997 en el juicio de Kansas vs Hendricks). En Chile en los 90 el caso del pedófilo apodado "Zacarach" sacó a la luz pública el tema que no se quería ver. En esa fecha se presentó al parlamento un proyecto de Ley para "curar" la pedofilia con acetato de Medroxiprogesterona imitando legislación de EE.UU. Causó sorpresa en el medio endocrinológico que se usara terapia hormonal como "cura" de la pedofilia. Se ha utilizado en varios países la castración química producida por gestágenos o agonístas del GnRH más antiandrógenos (acetato de Ciproterona), para inhibir la secreción y acción de la testosterona disminuyendo líbido y erección. No se ha demostrado que exista curación de la orientación pedófila y existen dudas de la prevención primaria y secundaria de la pedofilia. Pese al adelanto tecnológico en neurociencias para estudio de las zonas vinculadas a la sexualidad, aún no existen marcadores que permitan diagnosticar o pronosticar futuros resultados de la terapia. El tratamiento médico de la pedofilia no garantiza curación ni prevención del delito pedofílico.

Historically, society has rejected sexual abuse of children under 13, with there having been laws enacted in this regard. The judicial system, after a due process, condemned the perpetrator with reclusion and even up until the decades of the 70s and 80s with orchiectomy. Advances in neurobiology, endocrinology, psychopharmacology and psychology were considered the basis for treating the pedophile and putting them on probation, saving the financial cost of imprisonment for life. Multiple countries have enacted laws against pedophilic behaviour. Such legislation was greatly influenced by the enactment in the USA (state of Washington "on the sex offender" and the ruling of the Supreme Court in 1997 in the trial of Kansas against Hendricks). In Chile in the 90s, the case of a pedophile nicknamed "Zacarach" brought to light an issue that nobody wanted to see. Around that time, a bill was presented to Parliament to try and "cure" pedophilia with Medroxyprogesterone acetate, imitating US legislation. It was a surprise in the endocrinological world that hormonal therapy would be used as a "cure" for pedophilia. Chemical castration produced by gestagens or GnRH agonists plus antiandrogens (Cyproterone acetate) has been used in several countries to inhibit the secretion and action of testosterone, reducing libido and erection. It has not been proven that there is a cure for pedophile orientation and there are doubts about the primary and secondary prevention of pedophilia. Despite technological advances in neurosciences for the study of the zones pertaining to sexuality, there are still no indicators that allow for diagnosis or prediction of future results of therapy. The medical treatment of pedophilia does not guarantee cure or prevention of pedophilic crime.

Influence of statins in metastatic castration-resistant prostate cancer patients treated with new antiandrogen therapies: a systematic review and meta-analysis

ABSTRACT Objective To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic castration-resistant prostate cancer. Methods We searched studies in English language including the keywords statins, overall survival, and metastatic castration-resistant prostate cancer, at PubMed® (MEDLINE®), Embase and Cochrane databases. Results A total of 195 articles were initially identified, but only four met the inclusion criteria and were selected for the meta-analysis. A total of 955 patients, 632 on the new antiandrogens only group, and 323 on the new antiandrogens + statins group, were analyzed. In all four studies the combination therapy (new antiandrogens + statin) was well tolerated, regardless of which new antiandrogens were used. Neither the type of statin nor the doses and duration of use were well specified in the studies. The combination therapy in metastatic castration-resistant prostate cancer was associated with an overall survival improvement, and a 46% reduction in death (hazard ratio of 0.54; 95%CI 0.34-0.87; p<0.01) in multivariate analysis. Conclusion There seems to be a clinical benefit with the association of statins to the new antiandrogens in patients with metastatic castration-resistant prostate cancer, suggesting longer overall survival with no important collateral effect. However, due to fragility of the studies available in the literature, we are not yet capable of recommending this combination of drugs in the clinical practice. Further randomized prospective studies are warranted to confirm these beneficial outcomes.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Complete androgen blockade vs. medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).@*METHODS@#Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.@*RESULTS@#A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60-1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14-1.00, P = 0.0497).@*CONCLUSION@#Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Caracterización y evolución clínica de los pacientes con cáncer de próstata metastásico resistente a la castración atendidos en el servicio de urología de SOLCA (Guayaquil). 2013 a 2019 / Characterization and clinical evolution of patients with castration-resistant metastatic prostate cancer treated at the urology service of SOLCA (Guayaquil). 2013 to 2019

Introducción: El cáncer de próstata constituye la segunda neoplasia más frecuente después del cáncer pulmonar. Es la Primera causa de incidencia de cáncer en la población ecuatoriana, mientras que la mortalidad ocupó el segundo lugar. Enzalutamida retrasa significativamente la necesidad de quimioterapia y la disminución de la calidad de vida. En algunos estudios se ha encontrado disminu-ción del riesgo de muerte y retraso en el inicio de la quimioterapia así como aumento de la supervi-vencia post-quimioterapia con su uso. El objetivo del presente estudio fue caracterizar la evolución clínica de pacientes con cáncer de próstata metastásico resistente a la castración (mCRPC) tratados con enzalutamida. Metodología: Se recopiló información de pacientes atendidos en el servicio de Urología de Solca - Guayas del año 2013 al 2019. Se incluyeron todos los casos con cáncer de próstata metastásico resistente a la castración. Resultados: El promedio de edad fue de 77.3 ± 9.9 años. El tamaño inicial prostático fue de 59.9 ± 43.7 g. Los síntomas con mayor frecuencia registrados fueron: hematuria 18,8%, disminución del chorro miccional 18.8%, polaquiuria y poliuria con 14.6% cada uno. . La supervivencia global fue del 80% en los casos tratados con enzalutamida. Ninguna muerte estuvo asociada con el uso de enzalu-tamida. En el 66,6% se registraron eventos adversos. De todos los eventos adversos registrados el 82.3% fueron leves. Conclusión: La supervivencia global en el grupo estudiado estuvo acorde a los reportes de supervivencia en pacientes tratados con enzalutamida. La terapia con enzalutamida fue bien tolerada.

Introduction: Prostate cancer is the second most common neoplasm after lung cancer. It is the leading cause of cancer incidence in the Ecuadorian population, while mortality ranked second. En-zalutamide significantly delays the need for chemotherapy and decreases the quality of life. Some studies have found a decrease in the risk of death and a delay in the start of chemotherapy, as well as an increase in post-chemotherapy survival with its use. The aim of this study was to characterize the clinical course of patients with metastatic castration resistant prostate cancer (mCRPC) treated with enzalutamide. Methodology: Information was collected from patients treated in the Urology services of Solca - Guayas from 2013 to 2019. All cases with metastatic castration-resistant prostate cancer were in-cluded. Results: The mean age was 77.3 ± 9.9 years. The initial prostate size was 59.9 ± 43.7 g. The symp-toms with the highest frequency recorded were: hematuria 18.8%, decreased voiding stream 18.8%, frequency and polyuria with 14.6% each. Overall survival was 80% in the cases treated with enzalu-tamide. No deaths were associated with the use of enzalutamide. Adverse events were recorded in 66.6%. Of all the adverse events recorded, 82.3% were mild. Conclusion: The overall survival in the studied group was consistent with the survival reports in patients treated with enzalutamide. Enzalutamide therapy was well tolerated.

Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer / 北京大学学报(医学版)

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Mortality of motorcyclists due to traffic injuries in Brasil: a population-based study in Brazilian capitals

SUMMARY OBJECTIVE: To analyze the mortality trend of young men who were victims of traffic injuries involving motorcycles in all Brazilian capitals from 2001 to 2015. METHODS: A time-series study on all deaths of men aged 20-39 years old due to traffic injuries involving motorcycles in all 27 Brazilian capitals. We used the joinpoint regression model for temporal analysis and calculated the Annual Percent Change (APC) and Average Annual Percent Change (AAPC) to verify the mortality trends. RESULTS: A total of 12,058 deaths of young men were recorded in the Brazilian capitals during the period studied. The highest mortality rates were observed in Boa Vista/Roraima (34.0/100,000 population) and Palmas/Tocantins (29.80/100,000). Twelve of the 27 capitals showed an increasing trend in mortality, with the highest percentage increase being observed in Salvador (APC: 29.0%) and São Paulo (APC: 13.1%). None of the capitals showed a decline in the trend of mortality. CONCLUSIONS: Overall, the mortality of young men from traffic injuries involving motorcycles shows an increasing trend in 12 of the 27 capitals, which represents a public health problem that requires the implementation of more effective public policies.

RESUMO OBJETIVO: Analisar a tendência temporal da mortalidade de homens jovens vítimas de acidente de trânsito envolvendo motocicletas em todas as capitais brasileiras de 2001 a 2015. MÉTODOS: Estudo de séries temporais incluindo as mortes de homens de 20 a 39 anos por lesões no trânsito envolvendo motocicletas nas 27 capitais brasileiras. Para a análise, foi utilizado o modelo de regressão do ponto de inflexão e calculada a Variação Percentual Anual (APC) e a Variação Percentual Anual Média (AAPC). RESULTADOS: Foram registradas 12.058 mortes de homens jovens nas capitais brasileiras durante o período estudado. As maiores taxas de mortalidade foram observadas em Boa Vista/Roraima (34,0/100.000 habitantes) e Palmas/Tocantins (29,80/100.000). Doze capitais apresentaram tendência crescente de mortalidade, sendo o maior aumento percentual em Salvador (APC: 29,0%) e São Paulo (APC: 13,1%). Nenhuma das capitais mostrou declínio nas taxas. CONCLUSÕES: A mortalidade de jovens por lesões no trânsito envolvendo motocicletas tem mostrado uma tendência crescente em 12 capitais, o que representa um problema de saúde pública que requer a implementação de políticas públicas mais eficazes.

Clinical and surgical assistance in prostate cancer during the COVID-19 Pandemic: implementation of assistance protocols

ABSTRACT 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.

Special emphasis on bone health management in prostate cancer patients: a prospective longitudinal study

ABSTRACT Introduction: Use of androgen deprivation therapy (ADT) in carcinoma prostate (CaP) has deleterious effect on bone mineral density (BMD) leading to increase incidence of osteoporosis and skeletal-related events. We evaluated bone health status and impact of bone-directed therapy (BDT) and ADT on BMD in these patients from Jan 2015-Dec 2018. Materials and Method: Baseline bone health was assessed using Tc-99 MDP Bone scan/ DEXA scan for patients on ADT. Monthly zoledronic acid (ZA) was given to high-risk candidates (T-score ≤2.5 or previous hip/vertebral fracture) or Skel et al. metastatic patients who were receiving ADT. Baseline and follow-up (at 12-months) BMD using DEXA scan at various sites (spine, femur total, femur neck and radius) and subjective improvement in bony pain using Numeric Pain Rating Score after administration of ZA were compared. Results: A total of 96-patients of locally advanced and metastatic prostate cancer receiving ADT with or without BDT were included in the study cohort. Mean age of presentation was 68.4±15.61 years. Median serum PSA was 32.2±13.1ng/mL. There was significant improvement in mean BMD (T-score) in 64-patients post ZA therapy at 12-months (at femoral total, femoral neck and spine; 0.95, 0.79 and 0.68, respectively) (p <0.05) while there was significant deterioration in mean BMD at 12-months (at spine, femoral neck and femoral total; −0.77, −0.55 and −0.66, respectively) in 32 patients who did not receive ZA and were on ADT (p <0.05). Pain scores significantly decreased in patients after 12-months of ZA use (−2.92±2.16, p <0.01). Conclusion: Bone-directed therapy (Zoledronic acid) leads to both subjective and objective improvement in bone health of prostate cancer patients on ADT.

Efficacy of Leuprorelide acetate (Eligard®) in daily practice in Brazil: a retrospective study with depot formulations in patients with prostate cancer

ABSTRACT Introduction: Androgen deprivation therapy (ADT) is the mainstay of therapy for advanced prostate cancer. Studies addressing the efficacy of different depot formulations of long acting luteinizing hormone releasing hormone agonists in the Brazilian population are lacking. We aimed to compare the efficacy of three schedules of leuprolide acetate in lowering PSA in a real world population. Materials and Methods: We reviewed the medical records of patients with prostate cancer seen at our institution between January 2007 and July 2018. We analyzed patients treated with long-acting leuprolide acetate and grouped these patients into three strata according to the administration of ADT every 1, 3 or 6 months. The primary outcome was the serum prostate specific antigen (PSA) levels at 6 and 12 months after treatment initiation. We used Friedman test to compare the distribution of PSA levels at baseline and at 6 and 12 months within each treatment stratum. We considered two-sided P values <0.05 as statistically significant. We analyzed toxicity descriptively. Results: We analyzed a total of 932 patients, with a median age of 72 years and a median time since diagnosis of prostate cancer of 8.5 months. ADT was administered monthly in 115 patients, quarterly in 637, and semiannually in 180. Nearly half of the patients had locally advanced disease. In comparison with baseline, median serum PSA levels were reduced at 12 months by at least 99.7% in the three strata (P <0.001 in all cases). Sexual impotence and hot flashes were the most frequently reported toxicities. Conclusion: To our knowledge, this is the largest assessment of real-world data on alternative schedules of leuprolide in a Brazilian population. Our study suggests that PSA levels can be effectively be reduced in most patients treated with monthly, quarterly, or semiannual injections of long-acting leuprolide acetate.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Salud ósea en personas transgénero / Bone health in transgender subjects

Una persona transgénero es aquella en la cual el género autopercibido difiere del asignado al nacer, mientras que el término cisgénero es utilizado en aquellos individuos no trans. El tratamiento hormonal cruzado (THC) constituye una opción para lograr caracteres sexuales secundarios deseados. Es conocido que los esteroides sexuales desempeñan un rol fundamental en la adquisición de la densidad mineral ósea (DMO) durante la pubertad. Por lo tanto, el impacto del THC sobre la masa ósea se ha convertido en materia de estudio. En estadios puberales tempranos, los análogos de la hormona liberadora de gonadotrofinas (GnRH) son utilizados con un efecto reversible. Si bien la DMO parece mantenerse estable, cuando se compara con una población de referencia del mismo sexo biológico y edad, el Z-score se encuentra por debajo de lo esperado. En adultos, durante el THC no se informaron disminuciones en la DMO. Está reportado que las mujeres trans antes del inicio del TH presentan características densitométricas diferentes de los hombres cisgénero. Hasta el momento, la carga de datos para los calculadores del riesgo de fractura y el software del equipo DXA se basan en el sexo biológico y no en identidad de género. Recientemente, la International Society for Clinical Densitometry (ISCD) emitió sus recomendaciones para la evaluación de la masa ósea en personas transgénero y en aquellos individuos no conformes con el género. Si bien la ISCD sugiere realizar la evaluación únicamente en aquellos pacientes con factores de riesgo, es de importancia realizar DXA basal, sobre todo en mujeres transgénero, para determinar el riesgo inicial de dicha población. En este artículo se revisa la evidencia disponible sobre el impacto del THC en la salud ósea de personas transgénero. (AU)

Cross sex hormone therapy (CSHT) in transgender women (TW) it is an option to achieve desired secondary sexual characteristics. It is known that sex steroids play a fundamental role in the acquisition of bone mineral density during puberty, in addition to determining a different characteristic bone pattern between both biological sexes. So the impact of affirming HT on bone is it has become in subject of study. In early pubertal stages, GnRH analogs are used with a reversible effect. Although bone mineral density (BMD) seems to remain stable, when compared with a reference population of the same biological sex and age, the Z-score is lower than expected. In adults, during CSHT no decreases in BMD were reported. However, it was reported that TW prior to starting CSHT present different densitometric characteristics than cisgender men. So far, the data load for the fracture risk calculators and DXA software is based on biological sex and not gender identity. Recently the ISCD issued its recommendations for the evaluation of bone mass in transgender subjects and in those non-conforming to gender. Although the ISCD suggests performing the evaluation only in those patients with risk factors, our group recognizes that baseline DXA, especially in TW, constitutes a useful tool to determine the initial risk of this population. Our proposal arises from our own experience and from that compiled in the international literature, where it is observed that even without starting CSHT, transgender women have lower BMD. DXA. This article reviews the available evidence regarding the effect of CSHT on health bone in transgender people. (AU)