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Clinical Genitourinary Cancer Oct 2023While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the... (Meta-Analysis)
Meta-Analysis Review
Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer: A meta-analysis of RCTs.
INTRODUCTION
While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.
METHODS
We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.
RESULTS
Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.
CONCLUSIONS
The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
Topics: Male; Humans; Abiraterone Acetate; Mineralocorticoids; Prednisone; Prostatic Neoplasms, Castration-Resistant; Hypokalemia; Cardiotoxicity; Antineoplastic Combined Chemotherapy Protocols; Hypertension; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37236862
DOI: 10.1016/j.clgc.2023.04.007 -
The association between zinc and prostate cancer development: A systematic review and meta-analysis.PloS One 2024Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or intake with prostate cancer development.
METHODS
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science until May 1, 2023. We included case-controls and cross-sectionals that measured zinc level and/or intake in patients with prostate cancer or cohorts that evaluated the association between zinc and prostate cancer development. Studies that did not have a healthy control group were excluded. Joanna Briggs Institute was used for quality assessment. Publication bias was evaluated using Egger's and Begg's tests and funnel plot.
RESULTS
Overall, 52 studies (n = 44 case controls, n = 4 cohorts, and n = 4 cross sectionals) with a total number of 163909 participants were included. Serum (standardized mean difference (SMD): -1.11; 95% confidence interval (CI): -1.67, -0.56), hair (SMD: -1.31; 95% CI: -2.19, -0.44), and prostatic fluid or tissue zinc levels (SMD: -3.70; 95% CI: -4.90, -2.49) were significantly lower in prostate cancer patients. There were no significant differences in nail zinc level and zinc intake between those with prostate cancer and healthy controls. There was no publication bias except for serum and hair zinc levels based on Begg's and Egger's tests, respectively. The mean risk of bias scores were 4.61 in case-controls, eight in cohorts, and seven in cross-sectionals.
CONCLUSIONS
Overall, high zinc levels might have a protective role in prostate cancer, which can be used as a therapeutic or preventive intervention. Future large-scale studies are needed to confirm the association.
Topics: Male; Humans; Zinc; Prostatic Neoplasms; Health Status; Nutritional Status; PubMed
PubMed: 38507438
DOI: 10.1371/journal.pone.0299398 -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003