The genomic and microenvironmental factors affecting neuroendocrine differentiation in prostate cancer induced by androgen deprivation therapy

Although advanced prostate cancer(PCa)can be initially controlled by androgen deprivation therapy(ADT),recurrence normally occurs due to the appearance of castration-resistant prostate cancer(CRPC).Neuroendocrine differentiation(NED)in PCa can be partly explained the androgen resistance and progression to CRPC.NED normally associates with more aggressive clinical behaviour and poor outcomes in PCa.Although more and more studies are performed on NED in PCa recent decades,the molecular profiles that are implicated in NED are still poorly elucidated.Of these studies,signaling factors involved in genomic and microenvironmental components are deeply researched and most likely to provide the potential therapeutic targets for advanced PCa with NED.In this article,we review the hypothesis about the origin of NE cells and the molecular mechanisms driving NED from the point of genomic and environmental views.In addition,we discuss the current potential therapeutic targets and ongoing clinical trails associated with these molecular factors for the treatment of NED patients induced by ADT.

Intermittent androgen deprivation therapy in patients with prostate cancer: Connecting the dots

Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate cancer.The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment costs.IADT may also delay the progression to castration-resistant prostate cancer.However,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials.Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and analysis.The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs.continuous androgen deprivation therapy for the treatment of prostate cancer.The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)burden.Based on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Prostate cancer （PCa） is the most common visceral malignancy in men with androgen deprivation therapy （ADT） the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data （up to 2 years） for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

Effect of androgen deprivation therapy on bone mineral density in prostate cancer patients

Aim: To evaluate the effect of androgen deprivation therapy (ADT) on bone mineral density (BMD) in prostate cancer patients. Methods: Forty-nine prostate cancer patients with their BMD determined were divided into two groups: the non-treated group included 21 patients before the commencement of ADT and the treated group, 28 patients, who had received ADT for more than 1 year. BMD was measured by dual energy X-ray absorptiometry (DEXA) in the lumbar spine (L2-4) and femoral neck. Results: Thirteen (62 %) non-treated and 23 (82 %) treated patients fulfilled the BMD criteria for osteopenia or osteoporosis. Z scores for age-matched control in lumbar spine and femoral neck were -0.9 ± 0.7 and -0.6 ± 0.5, respectively, in the treated group, and -1.8 ± 1.1 and-1.6 ± 1.0 , respectively, in the non-treated group, the differences between the two groups were highly significant (P<0.01). Conclusion: Prostate cancer patients who received ADT for more than 1 year had a significantly lower BMD in the lumbar spine and femoral neck than those before the beginning of ADT.

Adverse effects of androgen deprivation therapy in men with prostate cancer： a focus on metabolic and cardiovascular complications

Prostate cancer （PCa） is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy （ADT） is used in the management of locally advanced （improves survival） and metastatic （improves pain and quality of life） PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries.Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years.The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling.Although a partly remediation is accomplished at the beginning of treatment,some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching,from E-cadherin to N-cadherin,which is the hallmark of epithelial-mesenchymal transition.Diverse direct and indirect mechanisms are involved in this switching and consequently,the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells.Since E-cadherin represses invasive and migrative behaviors of the tumor cells,the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation.In this study,we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-βpathway.

Effects of Exercise on Cancer-related Fatigue and Quality of Life in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Meta-analysis of Randomized Clinical Trials

Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy,specifically cancer-related fatigue(CRF) and quality of life(QoL). Methods Systematic searches for randomized clinical trials(RCTs) evaluating the effects of exercise on CRF and QoL of prostate cancer patients receiving androgen deprivation therapy were carried out to identify the eligible studies from EMBASE,Pub Med and Cochrane library. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Standardized mean differences(SMD) and its 95% confidence interval(CI) were calculated. Results In all,10 RCTs involving 841 prostate cancer patients(448 of whom exercised and 393 did not) were included in this study. With respect to CRF,there was good consistency among different studies,and it was remarkably reduced in the exercise group(SMD=-0.32,95% CI:-0.45 to-0.18,P<0.00001,n=784). In regards to QoL,there was also good consistency among different studies,and it was also improved significantly in the exercise group(SMD=0.21,95% CI:0.08 to 0.34,P=0.002,n=841). Conclusion Exercise both reduced CRF and improved QoL in prostate cancer patients receiving androgen deprivation therapy.

Metastatic Prostate Cancer under Androgen Deprivation Therapy: Factors Influencing Castration Resistance

Objective: To evaluate the factors predicting the time to progression to castration-resistant in metastatic prostate cancer under Androgen Deprivation Therapy (ADT) in our center. Patients and Methods: This is a retrospective, descriptive, analytical study in a single center over a period of 2 years. It has interest patients followed for metastasized prostate cancer under ADT. The parameters studied were: epidemiological, clinical, paraclinical, prostate specific antigen (PSA) nadir, time to nadir (TTN) and their link with the castration resistance. Results: The frequency of castration resistant prostate cancer was 28 patients per year. The mean age was 70.4 ± 7.9 years. An ECOG score ≥ 3 was more common as was the cT2c stage. The median of the initial total PSA was 489.6 ng/ml (203.3;1653.2). All patients had adenocarcinoma. The International Society of Urological Pathology (ISUP) 1 was more frequent. Bone metastases were more frequent. The medians of nadir, TTN and the castration resistance were 19.3 ng/ml (3.7;102.1), 5.5 months (3;9) and 11 months (6;15.3), respectively. The Eastern Cooperative Oncology Group (ECOG) score, clinical stage, metastatic site, the nadir and its TTN influenced the DSR. Age, lymph node involvement, initial total PSA and Gleason score did not influence the castration resistance. Conclusion: ADT should be initiated as soon as possible before an attack of general and/or clinical stage advanced to delay resistance. A drilling should be associated with this hormone therapy as much as possible because of its gain on resistance.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

Combination therapy with androgen deprivation for hormone sensitive prostate cancer: A new frontier

Androgen deprivation therapy(ADT)has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer(PCa).However,this approach is rarely curative.Recent clinical trials have demonstrated that ADT combined with other agents,notably docetaxel and abiraterone,lead to improved survival.The mechanisms surrounding this improved cancer outcomes are incompletely defined.The response of cancer cells to ADT includes apoptosis and cell death,but a significant fraction remains viable.Our laboratory has demonstrated both in vitro and in vivo that cellular senescence occurs in a subset of these cells.Cellular senescence is a phenotype characterized by cell cycle arrest,senescenceassociated b-galactosidase(SA-b-gal),and a hypermetabolic state.Positive features of cellular senescence include growth arrest and immune stimulation,although persistence may release cytokines and growth factors that are detrimental.Senescent tumor cells generate a catabolic state with increased glycolysis,protein turnover and other metabolic changes that represent targets for drugs,like metformin,to be applied in a synthetic lethal approach.This review examines the response to ADT and the putative role of cellular senescence as a biomarker and therapeutic target in this context.

The role of radiotherapy in localised and locally advanced prostate cancer

For a patient suffering from non-metastatic prostate cancer,the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board,to be explained carefully to the patient to obtain his informed consent.External beam radiotherapy is now delivered by intensity modulated radiotherapy,considered as the gold standard.From a radiotherapy perspective,low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy,or brachytherapy if patients meet the required eligibility criteria.Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4e6 months of androgen deprivation therapy;intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health.High-risk prostate cancer,i.e.high-risk localized and locally advanced prostate cancer,requires intensity modulated radiotherapy with long-term(≥2 years)androgen deprivation therapy with luteinizing hormone releasing hormone agonists.Post-operative irradiation,either immediate or early deferred,is proposed to patients classified as pT3pN0,based on surgical margins,prostate-specific antigen values and quality of life.Whatever the techniques and their degree of sophistication,quality assurance plays a major role in the management of radiotherapy,requiring the involvement of physicians,physicists,dosimetrists,radiation technologists and computer scientists.The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation.A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.

Association of time to prostate-specific antigen nadir and logarithm of prostate-specific antigen velocity after progression in metastatic prostate cancer with prior primary androgen deprivation therapy

We investigated the association of time to prostate-specific antigen nadir （TTPN） and logarithm of prostate-specific antigen velocity after progression Log（PSAVAP） in metastatic prostate cancer with prior primary androgen deprivation therapy （ADT）. All metastatic prostate cancer patients treated with primary ADT from 2000 to 2009 were reviewed. Patients who developed disease progression were included in the subsequent analyses. Patients were categorized into three groups according to their TTPN： TTPN of 〈3 months, 3-17 months, and 〉17 months. We compared the Log（PSAVAP） between the different TTPN groups using Mann-Whitney U-test and Kruskal-Wallis test. Further multiple linear regression analyses on Log（PSAVAP） were performed to adjust for other potential confounding factors. Among 419 patients who were treated with primary ADT, 306 patients developed disease progression with a median follow-up of 28 months, Longer TTPN was associated with lower Log（PSAVAP） （P = 0.008） within all subgroup analyses （TTPN of 〈3 vs 3-17 months, P = 0.020; TTPN of 3-17 vs 〉17 months, P = 0.009; and TTPN of 〈3 vs 〉17 months, P = 0.001）. Upon multiple linear regression analyses, baseline PSA （regression coefficient 0.001, P = 0.045）, PSA nadir （regression coefficient 0.002, P = 0.040）, and TTPN （regression coefficient -0.030, P = 0.001） were the three factors that were significantly associated with Log（PSAVAP）. In conclusion, a longer TTPN was associated with lower Log（PSAVAP） in metastatic prostate cancer patients following primary ADT. TTPN cut-offs at 3 months and 17 months appeared to have prognostic significance in predicting Log（PSAVAP）. TTPN may serve as a good prognostic indicator in deciding the treatment strategy in patients with disease progression.

Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients

Androgen deprivation therapy （ADT） is the standard of care for patients with metastatic prostate cancer. However, whether serum testosterone levels, using a cut-off point of 50 ng d1-1, are related to the effective time of ADT in newly diagnosed prostate cancer patients remains controversial. Moreover, recent studies have shown that some patients may benefit from the addition of upfront docetaxel chemotherapy. To date, no studies have been able to distinguish patients who will benefit from the combination of ADT and docetaxel chemotherapy. This study included 206 patients who were diagnosed with metastatic prostate cancer and showed progression to castrate-resistance prostate cancer （CRPC）. Serum testosterone levels were measured prospectively after ADT for 1, 3, and 6 months. The endpoint was the time to CRPC. In univariate and multivariate analyses, testosterone levels 〈50 ng d1-1 were not associated with the effective time of ADT. Receiver operating characteristic and univariate analysis showed that testosterone levels of 〈25 ng d1-1 after the first month of ADT offered the best overall sensitivity and specificity for prediction of a longer time to CRPC （adjusted hazard ratio [HR], 1.46; 95% confidence interval [95% CI], 1.08-1.96; P = 0.013）. Our results show that serum testosterone level of 25 ng d1-1 plays a prognostic role in prostate cancer patients receiving ADT. A testosterone value of 25 ng dl-~ after the first month of ADT can distinguish patients who benefit from ADT effectiveness for only a short time. These patients may need to receive ADT and concurrent docetaxel chemotherapy.

Neuroendocrine Differentiation in the Progression of Prostate Cancer: An Update on Recent Developments

Neuroendocrine (NE) differentiation, either benign or malignant, is the hallmark of prostate cancer (PCa). Clusters of malignant NE cells are found in most prostate cancer cases. NE differentiation is among the non-mutually exclusive theories proposed to explain the progression to androgen independence of PCa. NE differentiation is usually associated with an increased aggressivity and invasiveness of prostate tumors and a poor prognosis. This review aims to present an overview of current knowledge on neuroendocrine differentiation in PCa to improve our understanding of tumour progression and androgen independence. The NE component represents an important therapeutic axis. Development of new generation of drugs that selectively target NE-like cells may lead to the development of new therapeutic modalities for advanced and hormone-refractory PCa.

Development and Initial Validation of the Novel Scale for Assessing Quality of Life of Prostate Cancer Patients Receiving Androgen Deprivation Therapy

Background：There has been no a specific scale to measure quality of life （QOL） for prostate cancer patients receiving androgen deprivation therapy （ADT） to date.This study aimed to develop and initially validate the scale to evaluate QOL for prostate cancer patients receiving ADT.Methods：The scale was developed following international recommendations.Moreover,the items were all generated through literature review and referenced questionnaires.After being reviewed by expert panelists,the revised scale was formed and then completed by a convenience sample of 200 prostate cancer patients from our hospital.Explore factor analysis （EFA） was applied to test the construct validity,then split-half reliability,Cronbach＆#39;s alpha,and test-retest reliability were applied to assess the reliability and stability of the scale.Results：The revised scale contained 22 items and a total of 200 participants had completed the scale.One hundred participants were randomly selected from the total 200 participants to perform EFA with varimax rotation on the revised scale,and ＆quot;hot flashes＆quot; item was deleted for low factor loading.We selected only 3 items from each factor,then,the final scale was formed with 18-items.We selected another 100 participants to perform the EFA again on the final scale.It was demonstrated that the structure with 6 factors explained 72.5% of total variance and factor loading value was above 0.40 in all items of the factors.Moreover,the split-half reliability coefficient,Cronbach＆#39;s alpha,and test-retest reliability coefficient were calculated to be 0.74,0.63,and 0.89,respectively,exhibiting good reliability on the whole.Conclusions：The scale was identified to be a valid and reliable instrument to measure QOL for prostate cancer patients receiving ADT.Moreover,further research is needed to overcome the potential drawbacks.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy:using whole-mount histopathology as reference standard

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)mm^(2)s^(−1))was significantly lower than that of CR/MRD([1.17±0.02]×10^(-3)mm^(2)s^(−1)),which was significantly lower than that of benign tissues([1.30±0.02]×10^(-3)mm^(2)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.

No increased risk of dementia in patients receiving androgen deprivation therapy for prostate cancer： a 5-year follow-up study

Prior studies suggested that the use of androgen deprivation therapy （ADT） in patients with prostate cancer （PC） might cause the impairment of cognitive function which is one of the common symptoms of dementia; however, the association between ADT and cognitive impairment still remains controversial. This retrospective cohort study aimed to investigate the relationship between ADT and subsequent risk of dementia using a population-based dataset, Data for this study were taken from the Taiwan （China） Longitudinal Health Insurance Database 2005. We included 755 PC patients who received ADT in the study cohort and 559 PC patients who did not receive ADT in the comparison cohort. Each patient was individually tracked for a 5-year period to define those who subsequently received a diagnosis of dementia. Results show that the incidence rates of dementia per 100 person-years were 2.35 （95% confidence interval [95% CI]： 1.82-2.98） and 1.85 （95% Ch 1.35-2.48） for PC patients who received ADT and those who did not receive ADT, respectively. The adjusted hazard ratio （HR） for dementia for PC patients who received ADT was 1.21 （95% Ch 0.82-1.78, P = 0,333） compared to those who did not receive ADT. In addition, the adjusted HRs for dementia for PC patients receiving ADT with gonadotropin-releasing hormone （GnRH） agonists and without GnRH agonists were 1.39 （95% Ch 0.80-2.40, P = 0.240） and 1.13 （95% CI： 0.75-1.71, P = 0.564）, respectively, compared to PC patients not receiving ADT. We concluded that there was no difference in the risk of subsequent dementia between PC patients who did and those who did not receive ADT.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer

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 84003 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.

Hematological changes during androgen deprivation therapy

Androgen deprivation therapy （ADT） has been associated with a plethora of adverse effects, consistent with the androgen dependency of multiple reproductive and somatic tissues. One such tissue is the hemopoietic system, and one of the most predictable consequences of ADT is the development of anemia. Although anemia caused by ADT is rarely severe, ADT is often given to frail, elderly men with increased susceptibility to anemia due to multiple other causes. ADT-associated anemia may contribute to fatigue and reduced quality of life （QoL） in such men, although this requires further study. While anemia is an independent risk factor of mortality in men with prostate cancer, it is not known whether treatment of ADT-associated anemia alters clinically important outcomes, or whether treatment affects mortality. Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia. However, assessment and treatment of more severe anemia may be required. This should be determined on an individual basis. In contrast to the weli-descrihed actions of ADT on erythropoiesis, its effect on other hemopoietic lineages has been less well elucidated. While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils, lymphocytes and platelets, the implications of these findings for men with prostate cancer receiving ADT require further studies.