Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China:A nationwide,multi-center,population-based cross-sectional study

Background:Cardiovascular disease(CVD)has emerged as the leading cause of death from prostate cancer(PCa)in recent decades,bringing a great disease burden worldwide.Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy(ADT).The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling.CVD was defined as myocardial infarction,arrhythmia,heart failure,stroke,ischemic heart disease,and others.CVD risk was estimated by calculating Framingham risk scores(FRS).Patients were accordingly divided into low-,medium-,and high-risk groups.χ2 or Fisher’s exact test was used for comparison of categorical variables.Results:A total of 4253 patients were enrolled in the present study.A total of 27.0%(1147/4253)of patients had comorbid PCa and CVD,and 7.2%(307/4253)had two or more CVDs.The enrolled population was distributed in six regions of China,and approximately 71.0%(3019/4253)of patients lived in urban areas.With imaging and pathological evaluation,most PCa patients were diagnosed at an advanced stage,with 20.5%(871/4253)locally progressing and 20.5%(871/4253)showing metastasis.Most of them initiated prostatectomy(46.6%,1983/4253)or regimens involving ADT therapy(45.7%,1944/4253)for prostate cancer.In the present PCa cohort,43.1%(1832/4253)of patients had hypertension,and half of them had poorly controlled blood pressure.With FRS stratification,as expected,a higher risk of CVD was related to aging and metabolic disturbance.However,we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT.This was in accordance with clinical practice,i.e.,aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery.Among patients who underwent medical castration,only 4.0%(45/1118)received gonadotropin releasing hormone antagonists,in stark contrast to the grim situation of CVD prevalence and risk.Conclusions:PCa patients in China are diagnosed at an advanced stage.A heavy CVD burden was present at the initiation of treatment.Patients who accepted ADT-related therapy showed an original higher risk of CVD,but the awareness of cardiovascular protection was far from sufficient.

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

With the development and introduction of immune checkpoint inhibitors(ICIs)in cancer patients,immune-related side effects have increasingly attracted attention.However,the risks of immune-related renal toxicity are poorly characterized.In this study,we performed a network meta-analysis(NMA)of ICI-related randomized clinical trials(RCTs)to elucidate the comparative risk of acute kidney injury(AKI)in cancer patients receiving different ICIs.We also sought to identify other factors potentially affecting the risk of AKI.PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021.Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data.We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups.We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis.Once significant heterogeneity was detected in a traditional direct meta-analysis,multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI.A total of 85 RCTs were included in this study.In the NMA for the risk of grade 1-5 and 3-5 AKI,ipilimumab showed a significantly higher risk than avelumab and durvalumab,whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab(N1I3)showed a significantly higher risk than other groups.In terms of treatment ranking,durvalumab±low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI,whereas N1I3,ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI.Compared with other cancers,renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI.The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy.In this NMA involving largescale up-to-date ICI trials,we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI.Based on data from the ICI arms of these trials,we also revealed several potential risk factors for immune-related AKI,including tumor type and treatment paradigm.

Consensus on safety management of novel hormonal therapy for advanced prostate cancer

Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.

SEMA3A-mediated crosstalk between prostate cancer cells and tumor-associated macrophages promotes androgen deprivation therapy resistance

Androgen deprivation therapy(ADT)is an important treatment strategy that can be used to delay the progression of prostate cancer.However,after an initial response,which varies significantly among patients,the disease eventually progresses despite the low levels of testosterone in the systemic circulation.1 The mechanism underlying the progression of prostate cancer to castration-resistant prostate cancer(CRPC)is not yet clear,and further investigation is needed.