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European Urology Focus Nov 2022European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with...
BACKGROUND
European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).
OBJECTIVE
To report the process for designing and implementing OPT programmes.
DESIGN, SETTING, AND PARTICIPANTS
Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.
RESULTS AND LIMITATIONS
Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15 ng/ml/cm are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16 515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well.
CONCLUSIONS
We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.
PATIENT SUMMARY
We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.
Topics: Humans; Male; Middle Aged; Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Early Detection of Cancer
PubMed: 35811285
DOI: 10.1016/j.euf.2022.06.008 -
International Journal of Molecular... Feb 2020Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly... (Review)
Review
BACKGROUND
Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly including indolent cancer. Availability of different therapeutic strategies which have a very different impact on the patient's quality of life suggested a strong need for tools able to identify clinically significant cancer at diagnosis. Multi-parametric magnetic resonance showed very good performance in pre-biopsy diagnosis. However, it is an expensive tool and requires an experienced radiologist. In this context, a simple blood-based test is worth investigating. In this context, researchers focused their attention on the development of a laboratory test able to minimize overdiagnosis without losing the identification of aggressive tumors.
RESULTS
Recent literature data on PCa biomarkers revealed a clear tendency towards the use of panels of biomarkers or a combination of biomarkers and clinical variables. Phi, the 4Kscore, and Stockholm3 as circulating biomarkers and the Mi-prostate score, Exo DX Prostate, and Select MD-X as urinary biomarker-based tests have been developed. In this scenario, phi is worthy of attention as a noninvasive test significantly associated with aggressive PCa.
CONCLUSIONS
Literature data showed that phi had good diagnostic performance to identify clinically significant (cs) PCa, suggesting that it could be a useful tool for personalized treatment decision-making. In this review, phi potentialities, limitations, and comparisons with other blood- and urinary-based tests were explored.
Topics: Animals; Biomarkers, Tumor; Biopsy; Humans; Kallikreins; Magnetic Resonance Imaging; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment
PubMed: 32053990
DOI: 10.3390/ijms21041184 -
Is Serum Prostate-Specific Antigen a Reliable Prostate Cancer Marker in Liver Transplant Candidates.Experimental and Clinical... Aug 2019In this study, we aimed to determine whether the prostate-specific antigen level is a reliable marker of prostate cancer in patients with hepatic insufficiency, based on...
OBJECTIVES
In this study, we aimed to determine whether the prostate-specific antigen level is a reliable marker of prostate cancer in patients with hepatic insufficiency, based on evaluation of alterations in serum prostate-specific antigen levels after liver transplant in patients with hepatic insufficiency.
MATERIALS AND METHODS
Medical records of all patients who underwent liver transplant at our hospital between January 2003 and June 2017 were retrospectively reviewed. Male patients who were > 40 years old with available pre- and posttransplant serum total prostate-specific antigen levels were included in the study.
RESULTS
Our study included 36 male patients with a mean age of 54.6 ± 5.3 years (range, 45-73 y) at the time of liver transplant. The mean pretransplant serum total prostate-specific antigen level was 0.75 ± 0.77 ng/mL, which was significantly lower than the mean posttransplant level of 1.29 ± 1.57 ng/mL (P < .05). The pretransplant serum total prostate-specific antigen level was measured a mean of 4.9 ± 5.4 months before liver transplant versus a mean 27.6 ± 16.3 months after transplant. Prostate-specific antigen velocity was 0.2 ng/mL/year. Biochemical tests of liver function, including the mean serum levels of bilirubin, international normalized ratio, and albumin, were normal after liver transplant at 1.37 ± 2.33 mg/dL, 1.22 ± 0.36, and 4.16 ± 0.69 g/dL, respectively.
CONCLUSIONS
Serum prostate-specific antigen levels may decrease in patients with hepatic insufficiency/cirrhosis; therefore, a low serum prostate-specific antigen level may not be a reliable marker for excluding prostate cancer in such patients. Transplant surgeons and clinicians must be aware of this so that all male transplant candidates > 40 years old are evaluated via digital rectal examination, regardless of the serum prostate-specific antigen level.
Topics: Aged; Humans; Kallikreins; Liver Diseases; Liver Transplantation; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Retrospective Studies
PubMed: 29619912
DOI: 10.6002/ect.2017.0259 -
Saudi Medical Journal Jul 2022To determine the prevalence and characterize prostate cancer (PC) cases in Aseer, Saudi Arabia.
OBJECTIVES
To determine the prevalence and characterize prostate cancer (PC) cases in Aseer, Saudi Arabia.
METHODS
This study involved 883 patients who consulted physicians in Aseer Central Hospital, Abha, Saudi Arabia, for prostate issues between the years 2008-2018. All patients underwent digital rectal examination and measurement of their serum prostate-specific antigen levels. For patients who presented abnormal digital rectal examination findings and elevated prostate-specific antigen levels, prostate biopsies were recommended. Specimens were histopathologically examined to differentiate between malignant and benign tumors.
RESULTS
Among the 883 included patients, 132 (15%) underwent a prostate biopsy and were found to have a tumor. Histopathological examination confirmed malignancy (PC) in 77 (8.7%) patients. The absolute majority of the patients diagnosed with PC (96%) were aged >60 years and almost all of them (92%) were found to have a high prostate-specific antigen level of >4 ng/ml.
CONCLUSION
Prostate cancer appears to be a serious disease in Aseer, Saudi Arabia. Further studies aimed at determining the causes of this type of cancer and understanding its mechanisms are warranted.
Topics: Biopsy; Humans; Male; Prevalence; Prostate-Specific Antigen; Prostatic Neoplasms; Saudi Arabia
PubMed: 35830998
DOI: 10.15537/smj.2022.43.7.20210758 -
The Journal of Urology Feb 2020Prostate specific antigen screening for prostate cancer has recently been challenged due to poor sensitivity. In addition to prostate cancer, a number of conditions...
PURPOSE
Prostate specific antigen screening for prostate cancer has recently been challenged due to poor sensitivity. In addition to prostate cancer, a number of conditions elevate prostate specific antigen, of which benign prostatic hyperplasia is most common. The objective of this study was to assess the positive predictive value of prostate specific antigen and prostate specific antigen density for prostate cancer risk following holmium laser enucleation of the prostate.
MATERIALS AND METHODS
We queried an institutional review board approved database of holmium laser enucleation of the prostate performed at Indiana University from 1999 to 2018 to identify 1,147 patients with prostate specific antigen data available after holmium laser enucleation. A total of 55 biopsies after enucleation were recorded. Demographics, prostate specific antigen, prostate volume and oncologic details were analyzed. The primary outcome was biopsy proven prostate cancer.
RESULTS
A total of 55 patients underwent transrectal ultrasound prostate biopsy for cause after holmium laser enucleation of the prostate. Cancer was identified in more than 90% of biopsied cases. Men with prostate specific antigen above 1 ng/ml at biopsy had a 94% probability of cancer detection and an 80% risk of clinically significant disease. Prostate specific antigen density above 0.1 ng/ml was associated with a 95% risk of cancer and an 88% risk of clinically significant cancer. Prostate specific antigen greater than 5.8 ng/ml or prostate specific antigen density greater than 0.17 ng/ml was universally associated with biopsy proven cancer.
CONCLUSIONS
Prostate specific antigen and prostate specific antigen density have high positive predictive value for prostate cancer risk after holmium laser enucleation of the prostate. Thresholds for biopsy should be lower than in patients who do not undergo holmium laser enucleation. Those who undergo that procedure and have prostate specific antigen above 1 ng/ml or prostate specific antigen density above 0.1 ng/ml are at higher risk for harboring clinically significant disease and should undergo biopsy. Referring physicians should be aware of these significant risk shifts.
Topics: Aged; Humans; Kallikreins; Lasers, Solid-State; Male; Monitoring, Physiologic; Organ Size; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 31487219
DOI: 10.1097/JU.0000000000000530 -
Long-term consequences of the USPSTF Grade D recommendation for prostate-specific antigen screening.Cancer Feb 2020
Topics: Advisory Committees; Aged; Early Detection of Cancer; Humans; Incidence; Male; Mass Screening; Middle Aged; Practice Guidelines as Topic; Preventive Health Services; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; United States
PubMed: 31794066
DOI: 10.1002/cncr.32605 -
JAMA Oncology Oct 2022Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of...
IMPORTANCE
Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population.
OBJECTIVE
To assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the US Veterans Health Administration Informatics and Computing Infrastructure for men aged 55 to 69 years who self-identified as non-Hispanic Black or non-Hispanic White and were diagnosed with intermediate-, high-, or very high-risk prostate cancer from January 1, 2004, to December 31, 2017. Data were analyzed from August 2021 to March 2022.
EXPOSURES
Prostate-specific antigen screening rate, defined as the percentage of years in which PSA screening was conducted during the 5 years before diagnosis of prostate cancer.
MAIN OUTCOMES AND MEASURES
The primary outcome was risk of PCSM among Black men and White men. The association between PSA screening and risk of PCSM was assessed using Fine-Gray regression analysis. Risk of PCSM was also assessed categorically among patients classified as having no prior PSA screening, some screening (less than annual), or annual screening in the 5 years before diagnosis.
RESULTS
The study included 45 834 veterans (mean [SD] age, 62.7 [3.8] years), of whom 14 310 (31%) were non-Hispanic Black men and 31 524 (69%) were non-Hispanic White men. The PSA screening rate was associated with a lower risk of PCSM among Black men (subdistribution hazard ratio [sHR], 0.56; 95% CI, 0.41-0.76; P = .001) and White men (sHR, 0.58; 95% CI, 0.46-0.75; P = .001). On subset analysis, annual screening (vs some screening) was associated with a significant reduction in risk of PCSM among Black men (sHR, 0.65; 95% CI, 0.46-0.92; P = .02) but not among White men (sHR, 0.91; 95% CI, 0.74-1.11; P = .35).
CONCLUSIONS AND RELEVANCE
In this cohort study, PSA screening was associated with reduced risk of PCSM among non-Hispanic Black men and non-Hispanic White men. Annual screening was associated with reduced risk of PCSM among Black men but not among White men, suggesting that annual screening may be particularly important for Black men. Further research is needed to identify appropriate populations and protocols to maximize the benefits of PSA screening.
Topics: Humans; Male; Middle Aged; Prostate-Specific Antigen; Cohort Studies; Retrospective Studies; Veterans; Early Detection of Cancer; Prostatic Neoplasms
PubMed: 35925581
DOI: 10.1001/jamaoncol.2022.2970 -
European Urology Mar 2023Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial.
BACKGROUND
Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo.
OBJECTIVE
To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo.
DESIGN, SETTING, AND PARTICIPANTS
A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted.
INTERVENTION
Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study.
RESULTS AND LIMITATIONS
Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26-0.55]; PSADT ≤6 mo, 0.41 [0.33-0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations.
CONCLUSIONS
In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability.
PATIENT SUMMARY
In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Androgen Antagonists
PubMed: 36089529
DOI: 10.1016/j.eururo.2022.07.018 -
Expert Review of Clinical Pharmacology Oct 2021: The proven efficacy of the cellular vaccine sipuleucel-T in 2010 led to optimism about immunotherapeutic approaches for the treatment of prostate cancer. Some surmised... (Review)
Review
: The proven efficacy of the cellular vaccine sipuleucel-T in 2010 led to optimism about immunotherapeutic approaches for the treatment of prostate cancer. Some surmised that prostate cancer might be an ideal target for immune-mediated killing given that the prostate is not an essential organ and expresses unique proteins including prostate-specific antigen, prostate-specific membrane antigen, and prostatic acid phosphatase that could be targeted without side effects. Subsequently, antibodies that inhibit the T cell checkpoints PD1 and CTLA4 were shown to stimulate antitumor immune responses, leading to tumor regression in several cancer types. These therapies have since been tested in several studies as treatments for prostate cancer, but appear to have limited efficacy in molecularly unselected patients.: In this review, we discuss these studies and evaluate features of prostate cancer and its host environment that may render it generally resistant to CTLA4 and PD1 blockade. We provide an overview of alternate immune checkpoints that may hold greater significance in this disease.: Combination therapies to target multiple layers of alternate immune checkpoints may be required for an effective immune response to prostate cancer. We discuss combination therapies currently being investigated.
Topics: Cancer Vaccines; Drug Resistance, Neoplasm; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Male; Molecular Targeted Therapy; Patient Selection; Prostate-Specific Antigen; Prostatic Neoplasms; Tissue Extracts
PubMed: 34263692
DOI: 10.1080/17512433.2021.1949287 -
Acta Bio-medica : Atenei Parmensis Jan 2022The Prostate Specific Antigen (PSA) is the first filter in the diagnosis of prostate cancer. Unfortunately, it is organ-specific but not cancer-specific. In addition,... (Review)
Review
The Prostate Specific Antigen (PSA) is the first filter in the diagnosis of prostate cancer. Unfortunately, it is organ-specific but not cancer-specific. In addition, some prostate cancers are not clinically-significant and their diagnosis and treatment may lead to overdiagnosis and overtreatment. For these reasons, other markers have been proposed in the last years, such as PCA3 and PHI, but none of these are currently used in the clinical practice on large scale. In the last decade, PSA-IgM and the algorithm iXip have emerged for the diagnosis of prostate cancer and showed to perform well in decreasing the detection of clinically-insignificant prostate cancer and in reducing the number of unnecessary prostate biopsies. This review focuses on data reported in the literature on PSA-IgM and iXip as well as on the future perspectives of their usage in the clinical practice on large scale.
Topics: Humans; Immunoglobulin M; Male; Overdiagnosis; Overtreatment; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 35075069
DOI: 10.23750/abm.v92i6.12058