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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 -
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 -
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 -
International Journal of Dermatology Mar 2023Hair lipid composition varies by ethnic hair type and by hair layer. Lipids in the cuticle, cortex, and medulla of the hair shaft provide a protective barrier to... (Review)
Review
Hair lipid composition varies by ethnic hair type and by hair layer. Lipids in the cuticle, cortex, and medulla of the hair shaft provide a protective barrier to environmental and chemical damage, prevent hair breakage and desorption, and affect the elastic and tensile properties of hair. The aim of this systematic review is to provide an overview of the lipid composition and ethnic differences of human hair, effects of external damage on lipid content and properties, and changes in hair lipid composition associated with disease states. PubMed/MEDLINE was searched up to March 2021 according to PRISMA guidelines for articles discussing the lipid content of human hair and effects of physical, chemical, or environmental damage, and disease. Fifty-nine articles investigating the lipid content of hair were included for review. Lipids affect fluid permeability, hydration, strength, and texture of ethnic hair fibers. Lipid loss is accelerated by hair-damaging treatments such as bleach, dye, perm, straightening, and surfactant use, and sun and aging processes, leading to dehydrated, breakable, disordered, and dull hair. Diseases including acne, alopecia, and breast, gastric, prostate, lung, and rectal cancers display elevated hair lipid levels. Lipids are vital in protection against damage and maintenance of healthy hair. Further studies are needed to investigate the effects of lipids on the structural properties of ethnic hair, and changes in hair lipid composition with various dermatologic and systemic diseases.
Topics: Humans; Hair; Breast; Permeability; Acne Vulgaris; Lipids
PubMed: 35218566
DOI: 10.1111/ijd.16109 -
The Aging Male : the Official Journal... Dec 2021Liquid biopsy refers to the detection and analysis of the components from biological fluids non-invasively, including circulating tumor cells, nucleic acids, and...
PURPOSE
Liquid biopsy refers to the detection and analysis of the components from biological fluids non-invasively, including circulating tumor cells, nucleic acids, and extracellular vesicles (EVs). It is necessary to review the clinical value of liquid biopsy assays in PC and explore its potential application.
MATERIALS AND METHODS
We systematically reviewed of PubMed was performed to identify relevant literature on potential clinical applications of circulating tumor cells, circulating nucleic acids, and EVs in prostate cancer (PC).
RESULTS
Liquid biopsy has emerged as a powerful tool to elucidate dynamic genomic, transcriptomic, and epigenomic tumor profiling in real-time. Here, the potential clinical applications of liquid biopsy include early detection, prognosis of survival, assessment of treatment response, and mechanisms of drug resistance in PC.
CONCLUSIONS
Liquid biopsy provides great value in diagnosis, prognosis, and treatment response in PC. Characterization of liquid biopsy components provides benefits both to unravel underlying resistance mechanisms and to exploit novel clinically actionable targets in PC. In addition, we suggest that analysis of multiparametric liquid biopsies should be analyzed comprehensively, assisting in monitoring tumor characteristics in real-time, guiding therapeutic selection, and early therapeutic switching during disease progression.
Topics: Biomarkers, Tumor; Humans; Liquid Biopsy; Male; Neoplastic Cells, Circulating; Prognosis; Prostatic Neoplasms
PubMed: 34850655
DOI: 10.1080/13685538.2021.1944085 -
World Journal of Urology Mar 2022Transurethral endoscopic procedures using bipolar current, or laser energy are nowadays widely accepted and have replaced the traditional monopolar resection. A major... (Review)
Review
PURPOSE
Transurethral endoscopic procedures using bipolar current, or laser energy are nowadays widely accepted and have replaced the traditional monopolar resection. A major advantage of these techniques is the utilization of isotonic saline as irrigation solution, which minimizes side effects such as symptoms associated to classical transurethral resection syndrome (TUR-syndrome). Nonetheless, clinically significant IFA also occurs with saline and is determined by pressure gradients, systemic resistance and by the amount of irrigation fluid. We aimed to investigate the extend of IFA and symptoms due to volume overload during bipolar transurethral resection (bTUR) and laser procedures of the prostate.
METHODS
We performed a systematic literature search using PubMed, restricted to original English-written articles, including animal, artificial model, and human studies. Search terms were TUR, transurethral, laser, HoLEP, ThuLEP, greenlight, enucleation, fluid absorption, fluid uptake, and TUR-syndrome.
RESULTS
Mean and maximum IFA during bTURP ranges between 133 and 915 ml and 1019 ml and 2166 ml, respectively. Absorption during laser procedures can be significant with maximum values up to 4579 ml and mainly occurs during prostate vaporization techniques. Incidence of moderate to severe symptoms from iso-osmolar volume overload reaches 9%.
CONCLUSIONS
Irrigation fluid absorption during bTUR and laser surgery of the prostate is not negligible. Iso-osmolar overhydration with development of non-classical TUR-syndrome should be identified peri- and postoperatively and surgical teams should be aware of complications. Breath ethanol, venous pH, serum chloride, and bicarbonate could be markers for detecting dangerous events of IFA with saline.
Topics: Humans; Laser Therapy; Lasers; Male; Prostate; Prostatic Hyperplasia; Therapeutic Irrigation; Transurethral Resection of Prostate; Urologic Surgical Procedures
PubMed: 34191108
DOI: 10.1007/s00345-021-03769-4 -
Frontiers in Endocrinology 2021Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes...
BACKGROUND
Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men.
OBJECTIVE
To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system.
METHODS
We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included.
RESULTS
We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA.
CONCLUSION
The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.
Topics: COVID-19; Genitalia, Male; History, 21st Century; Humans; Inflammation; Male; Prostate; SARS-CoV-2; Semen; Semen Analysis; Sexual Dysfunction, Physiological; Testis
PubMed: 34122351
DOI: 10.3389/fendo.2021.677701 -
The Spine Journal : Official Journal of... Nov 2021Limited studies have investigated risk factors for postoperative urinary retention (POUR) following elective spine surgery. Furthermore, some discrepancies have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND CONTEXT
Limited studies have investigated risk factors for postoperative urinary retention (POUR) following elective spine surgery. Furthermore, some discrepancies have been found in the results of existing observational studies.
PURPOSE
This study aimed to review the available literature on risk factors associated with POUR following elective spine surgery.
STUDY DESIGN
A systematic review with meta-analysis was performed.
PATIENT SAMPLE
A total of 31,251 patients (POUR=2,858, no POUR=28,393) were included in the meta-analysis.
OUTCOME MEASURES
Demographics, type of elective spine surgery, country, definition of POUR, and potential risk factors for POUR were evaluated.
METHODS
The Cochrane Library, Embase, and Medline electronic databases were searched to identify relevant studies. Binary outcomes were reported as odds ratio (OR). Weighted mean differences (WMD) or standardized mean differences (SMD), with 95% confidence intervals (CI), were used for meta-analysis of continuous outcomes.
RESULTS
Eleven studies (2 prospective and 9 retrospective) were included in the analysis. Patients with POUR were older than those without POUR (WMD, 7.13; 95% CI, 4.50-9.76). Male patients were found to have an increased risk of POUR (OR, 1.31; 95% CI, 1.04-1.64). The following variables were also identified as significant risk factors for POUR: benign prostatic hyperplasia (BPH; OR, 3.79; 95% CI, 1.89-7.62), diabetes mellitus (DM; OR, 1.50; 95% CI, 1.17-1.93), and previous urinary tract infection (UTI; OR, 1.70; 95% CI, 1.28-2.24). Moreover, longer operative time (WMD, 19.88; 95% CI, 5.01-34.75) and increased intraoperative fluid support (SMD, 0.37; 95% CI, 0.23-0.52) were observed in patients with POUR. In contrast, spine surgical procedures involving fewer levels (OR, 0.75; 95% CI, 0.65-0.86), and ambulation on the same day as surgery (OR, 0.65; 95% CI, 0.52-0.81) were associated with a decreased risk of POUR.
CONCLUSIONS
Based on our meta-analysis, older age, male gender, BPH, DM, and a history of UTI are risk factors for POUR following elective spine surgery. We also found that longer operative time and increased intravenous fluid support would increase the risk of POUR. Additionally, multi-level spine surgery may have a negative effect on postoperative voiding.
Topics: Aged; Humans; Male; Postoperative Complications; Prospective Studies; Retrospective Studies; Risk Factors; Spine; Urinary Retention
PubMed: 34015508
DOI: 10.1016/j.spinee.2021.05.009 -
Archivio Italiano Di Urologia,... Mar 2021Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2) was first identified by the Chinese Centers for Disease Control and Prevention on January 8, 2020 and was...
INTRODUCTION
Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2) was first identified by the Chinese Centers for Disease Control and Prevention on January 8, 2020 and was declared as a global pandemic on March 11, 2020 by WHO. SARS-CoV-2 uses the Angiotensin-converting enzyme 2 (ACE2) receptor as an entry route, associated with the transmembrane serine protease protein (TMPRSS2), which makes the testis and particularly spermatogenesis potentially vulnerable, since this tissue has high expression of ACE2.
MATERIAL AND METHODS
We performed a systematic literature review by electronic bibliographic databases in Pubmed, Scopus and ScienceDirect up to August 2020 about the effect of SARS-CoV-2 on male sexual function and its transmission, to assess possible repercussions on sex organs and the existence of a sexual transmission path.
RESULTS
Although SARS-CoV-2 presence has not been found in testicle samples, it has been demonstrated that it causes histological changes compatible with orchitis, and sex hormone disturbances. TMPRSS2 is up-regulated in prostate cancer where it supports tumor progression, thus these patients may have a higher risk of SARS-CoV-2 infection. TMPRSS2 inhibitors may be useful for the treatment or prevention of COVID-19. No viral material has been found in blood or semen, however it has been proven to be present in stool and saliva.
CONCLUSION
The male reproductive system would be highly vulnerable and susceptible to infection by SARS-CoV-2 given the expression of the ACE2 receptor in somatic and germ cells. The seminal fluid would remain free of viral presence in patients with COVID-19. Regardless, non-genital sex could be an important source of viral transmission. In assisted reproduction techniques all necessary tests must be carried out to ensure the donor is free of the virus at the time of collection and handling of the seminal sample.
Topics: COVID-19; Humans; Male; Sexual Dysfunction, Physiological; Sexually Transmitted Diseases, Viral; Testis
PubMed: 33754609
DOI: 10.4081/aiua.2021.1.48 -
F&S Reviews Apr 2021To determine if SARS-CoV-2, which has led to the rapidly spreading COVID-19 global pandemic, is sexually transmitted. Since the putative receptor for the virus is... (Review)
Review
OBJECTIVE
To determine if SARS-CoV-2, which has led to the rapidly spreading COVID-19 global pandemic, is sexually transmitted. Since the putative receptor for the virus is identified in reproductive organs, it is also important to examine if COVID-19 may affect human fertility.
EVIDENCE REVIEW
A systematic review of English publications was conducted up to December 11, 2020 in PubMed, NIH iCite COVID-19 portfolio, Cochrane Library, and Google Scholar databases, searching for SARS-CoV-2 in the testes; seminal, prostatic, and vaginal fluids; and cervical smears. A total of 1,997 records were identified, duplicates were removed, and 1,490 records were reviewed for eligibility by examining titles and abstracts. Subsequently, 202 full-text relevant articles were reviewed by 2 independent reviewers. Forty-seven studies (literature reviews, editorials, and guidelines) were assessed qualitatively, and 23 studies that tested the male and female reproductive tracts of patients with COVID-19 for SARS-CoV-2 were quantitatively analyzed.
RESULTS
No epidemiological investigations to date have described evidence suggesting that COVID-19 is an STD. While angiotensin-converting enzyme 2 receptor is found in the reproductive organs, the lack of co-expression of the TMPRSS2 modulatory protein, required for SARS-CoV-2 cell entry, in testicular cells, sperm, or oocytes, argues against the hypothesis that gametes transmit SARS-CoV-2. Molecular detection studies of SARS-CoV-2 RNA in the male and female reproductive tracts were summarized: 98.0% (293/299) of the seminal fluids, 16/17 testicular biopsies, all 89 prostatic fluids, 98.3% (57/58) of the vaginal fluids, all 35 cervical smears, and all 16 oocyte samples tested negative for SARS-CoV-2. None of the studies confirmed sexual transmission of SARS-CoV-2. Nonetheless, COVID-19 may have detrimental effects on male reproduction by inducing orchitis and/or decreasing testosterone levels, sperm counts, and motility.
CONCLUSION
On the basis of the current worldwide published information, COVID-19 is not an STD. This information is important for clinicians, proposed guidelines for public health, U.S. Food and Drug Administration guidelines for gamete and tissue donor eligibility, and fertility treatments. Universal precautions, currently practiced worldwide, are adequate and sufficient at this time to prevent the transmission of known or unknown viral infections. We suggest that recovered patients of COVID-19, especially those with infertility, should be evaluated for their ovarian and testicular function.
PubMed: 33558864
DOI: 10.1016/j.xfnr.2021.01.002