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The Medical Clinics of North America Nov 2020This article gives an overview of the current state of the evidence for prostate cancer early detection with prostate-specific antigen (PSA) and summarizes current... (Review)
Review
This article gives an overview of the current state of the evidence for prostate cancer early detection with prostate-specific antigen (PSA) and summarizes current recommendations from guideline groups. The article reviews the global public health burden and risk factors for prostate cancer with clinical implications as screening tools. Screening studies, novel biomarkers, and MRI are discussed. The article outlines 7 key practice points for primary care physicians and provides a simple schema for facilitating shared decision-making conversations.
Topics: Humans; Male; Primary Health Care; Prostate-Specific Antigen; Prostatic Neoplasms; United States
PubMed: 33099450
DOI: 10.1016/j.mcna.2020.08.007 -
Clinical Chemistry and Laboratory... Feb 2020In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely... (Review)
Review
In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate cancer is controversial. Several expert panels, however, have recently recommended limited PSA screening following informed consent in average-risk men, aged 55-69 years. As a screening test for prostate cancer however, PSA has limited specificity and leads to overdiagnosis which in turn results in overtreatment. To increase specificity and reduce the number of unnecessary biopsies, biomarkers such as percent free PSA, prostate health index (PHI) or the 4K score may be used, while Progensa PCA3 may be measured to reduce the number of repeat biopsies in men with a previously negative biopsy. In addition to its role in screening, PSA is also widely used in the management of patients with diagnosed prostate cancer such as in surveillance following diagnosis, monitoring response to therapy and in combination with both clinical and histological criteria in risk stratification for recurrence. For determining aggressiveness and predicting outcome, especially in low- or intermediate-risk men, tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris and ProMark, may be used. Emerging therapy predictive biomarkers include AR-V7 for predicting lack of response to specific anti-androgens (enzalutamide, abiraterone), BRAC1/2 mutations for predicting benefit from PARP inhibitor and PORTOS for predicting benefit from radiotherapy. With the increased availability of multiple biomarkers, personalised treatment for men with prostate cancer is finally on the horizon.
Topics: Biomarkers, Tumor; Humans; Male; Mass Screening; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment
PubMed: 31714881
DOI: 10.1515/cclm-2019-0693 -
Cancer Biology & Therapy Dec 2022In the last decade, many life-prolonging therapeutic options have emerged for metastatic castration-resistant prostate cancer (mCRPC). The recent VISION trial is the...
In the last decade, many life-prolonging therapeutic options have emerged for metastatic castration-resistant prostate cancer (mCRPC). The recent VISION trial is the first to demonstrate a survival benefit of Lutetium-177[Lu]Lu-PSMA-617 in post-chemotherapy mCRPC. This journal club reviews the VISION trial in the context of the earlier TheraP trial of [Lu]Lu-PSMA-617 in mCRPC post docetaxel and androgen pathway inhibition, to provide direction for the real-world application of [Lu]Lu-PSMA-617. Treatment in the control groups differed significantly between both trials and may have influenced outcomes: TheraP mandated cabazitaxel whereas VISION's design could not allow it. In both trials, [Lu]Lu-PSMA-617 had a good safety profile, with common adverse events being fatigue, nausea, dry mouth, marrow suppression and diarrhea. Given its efficacy and favorable safety even in heavily pre-treated patients, [Lu]Lu-PSMA-617 provides hope to mCRPC patients and may be applied to earlier disease stages in future investigations.
Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 35220877
DOI: 10.1080/15384047.2022.2037985 -
Nature Cancer May 2023Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms...
Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with F-fluciclovine uptake on positron emission tomography imaging. While PSMA is regulated by AR, we identified a subset of AR-negative CRPC with high PSMA. HOXB13 and AR co-occupancy at the PSMA enhancer and knockout models point to HOXB13 as an upstream regulator of PSMA in AR-positive and AR-negative prostate cancer. These data demonstrate how PSMA expression is differentially regulated across metastatic lesions and in the context of the AR, which may inform selection for PSMA-targeted therapies and development of complementary biomarkers.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Prostate; Prostate-Specific Antigen; Positron-Emission Tomography; Tumor Microenvironment
PubMed: 37038004
DOI: 10.1038/s43018-023-00539-6 -
Nutrients Mar 2022(1) Background: Increasing evidence indicates that lipid metabolism may influence the concentration of prostate-specific antigen (PSA). However, the association between...
(1) Background: Increasing evidence indicates that lipid metabolism may influence the concentration of prostate-specific antigen (PSA). However, the association between triglycerides and PSA remains unclear and complicated. Hence, we evaluated the correlation between triglycerides and PSA based on the U.S. National Health and Nutrition Examination Survey (NHANES) database. (2) Methods: A total of 2910 participants out of 41,156 participants fit into our study after conducting the screening from the 2003 to 2010 NHANES survey. Serum triglycerides were the independent variable of our study, and PSA was the dependent variable; (3) Results: In our study, the average age of chosen participants was 59.7 years (±12.7). After adjusting for covariates, the result indicated that for each additional unit of serum triglyceride (mg/dL), the PSA concentrations were reduced by 0.0043 ng/mL (-0.0082, -0.0005) with a statistical difference. Furthermore, we used machine learning of the XGBoost model to determine the relative importance of selected variables as well as constructed a smooth curve based on the fully adjusted model to investigate the possible linear relationship between the triglyceride and PSA concentrations. (4) Conclusions: The serum triglyceride is independently and negatively correlated with PSA among American males, which may make it hard to detect asymptomatic prostate cancer and diagnose at an advance stage with higher triglycerides due to detection bias.
Topics: Humans; Male; Mass Screening; Middle Aged; Nutrition Surveys; Prostate-Specific Antigen; Prostatic Neoplasms; Triglycerides; United States
PubMed: 35405939
DOI: 10.3390/nu14071325 -
European Urology Focus Mar 2020Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in...
Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in prognostication, the European Association of Urology prostate cancer guidelines panel undertook a systematic review and successfully developed a novel BCR risk stratification system (groups with a low risk or high risk of BCR) based on disease and prostate-specific antigen characteristics. PATIENT SUMMARY: Following treatment to cure prostate cancer, some patients can develop recurrence of disease identified via a prostate-specific antigen blood test (ie, biochemical recurrence, or BCR). However, not every man who experiences BCR develops progressive disease (symptoms or evidence of disease progression on imaging). We conducted a review of the literature and developed a classification system for predicting which patients might progress to optimize treatment decisions.
Topics: Humans; Male; Neoplasm Recurrence, Local; Practice Guidelines as Topic; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment
PubMed: 31248850
DOI: 10.1016/j.euf.2019.06.004 -
Cancer Discovery Jan 2024Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing...
UNLABELLED
Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
SIGNIFICANCE
Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Nolan-Stevaux et al., p. 90. This article is featured in Selected Articles from This Issue, p. 5.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Immunotherapy; Treatment Outcome; Antigens, Neoplasm; Oxidoreductases
PubMed: 37861461
DOI: 10.1158/2159-8290.CD-23-0964 -
Endocrinology, Diabetes & Metabolism May 2023Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism,...
BACKGROUND
Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males.
METHODS
In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response.
RESULTS
In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found.
CONCLUSION
Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.
Topics: Child; Humans; Male; Testosterone; Retrospective Studies; Prostate-Specific Antigen; Clomiphene; Hypogonadism; Luteinizing Hormone; Follicle Stimulating Hormone
PubMed: 36998229
DOI: 10.1002/edm2.416 -
The Prostate Aug 2022An important fraction (>/~10%) of men with high-risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely... (Review)
Review
BACKGROUND
An important fraction (>/~10%) of men with high-risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases.
AIMS
Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications.
RESULTS
The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings.
DISCUSSION
The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.
Topics: Early Detection of Cancer; Genetic Predisposition to Disease; Germ Cells; Germ-Line Mutation; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 35657157
DOI: 10.1002/pros.24340 -
JAMA Network Open Apr 2023The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the...
IMPORTANCE
The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the risk of false-positive results and overdiagnosis of indolent disease. However, this low-value PSA screening in males aged 70 years or older remains common.
OBJECTIVE
To characterize the factors associated with low-value PSA screening in males 70 years or older.
DESIGN, SETTING, AND PARTICIPANTS
This survey study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide annual survey conducted by the Centers for Disease Control and Prevention that collects information via telephone from more than 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. The final cohort comprised male respondents to the 2020 BRFSS survey who were categorized into the following age groups: 70 to 74 years, 75 to 79 years, or 80 years or older. Males with a former or current prostate cancer diagnosis were excluded.
MAIN OUTCOMES AND MEASURES
The outcomes were recent PSA screening rates and factors associated with low-value PSA screening. Recent screening was defined as PSA testing within the past 2 years. Weighted multivariable logistic regressions and 2-sided significance tests were used to characterize factors associated with recent screening.
RESULTS
The cohort included 32 306 males. Most of these males (87.6%) were White individuals, whereas 1.1% were American Indian, 1.2% were Asian, 4.3% were Black, and 3.4% were Hispanic individuals. Within this cohort, 42.8% of respondents were aged 70 to 74 years, 28.4% were aged 75 to 79 years, and 28.9% were 80 years or older. The recent PSA screening rates were 55.3% for males in the 70-to-74-year age group, 52.1% in the 75-to-79-year age group, and 39.4% in the 80-year-or-older group. Among all racial groups, non-Hispanic White males had the highest screening rate (50.7%), and non-Hispanic American Indian males had the lowest screening rate (32.0%). Screening increased with higher educational level and annual income. Married respondents were screened more than unmarried males. In a multivariable regression model, discussing PSA testing advantages with a clinician (odds ratio [OR], 9.09; 95% CI, 7.60-11.40; P < .001) was associated with increased recent screening, whereas discussing PSA testing disadvantages had no association with screening (OR, 0.95; 95% CI, 0.77-1.17; P = .60). Other factors associated with a higher screening rate included having a primary care physician, a post-high school educational level, and income of more than $25 000 per year.
CONCLUSIONS AND RELEVANCE
Results of this survey study suggest that older male respondents to the 2020 BRFSS survey were overscreened for prostate cancer despite the age cutoff for PSA screening recommended in national guidelines. Discussing the benefits of PSA testing with a clinician was associated with increased screening, underscoring the potential of clinician-level interventions to reduce overscreening in older males.
Topics: Humans; Male; Aged; Aged, 80 and over; Early Detection of Cancer; Low-Value Care; Prostate-Specific Antigen; Prostatic Neoplasms; Surveys and Questionnaires; Cohort Studies; False Positive Reactions
PubMed: 37040113
DOI: 10.1001/jamanetworkopen.2023.7504