-
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 -
American Society of Clinical Oncology... Apr 2022Biochemical recurrence develops in almost one-third of men with prostate cancer after treatment with local therapy. There are numerous options for management, including... (Review)
Review
Biochemical recurrence develops in almost one-third of men with prostate cancer after treatment with local therapy. There are numerous options for management, including surveillance, salvage radiation, androgen deprivation therapy (ADT), and clinical trials. This article reviews the current approaches to radiation therapy, ADT, and molecular imaging in men with biochemically recurrent prostate cancer. First, radiation therapy, including selection of field, dose, and use of concurrent antiandrogen therapy, is reviewed. Next, molecular imaging is addressed, including prostate-specific membrane antigen PET imaging and its increased sensitivity in identifying sites of disease. Finally, the factors associated with starting ADT are explored, and the data supporting intermittent over continuous ADT are reviewed. Lastly, the use of prostate-specific membrane antigen PET imaging and its potential role influencing therapy are discussed.
Topics: Androgen Antagonists; Combined Modality Therapy; Humans; Male; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy
PubMed: 35503984
DOI: 10.1200/EDBK_351033 -
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 -
Molecules (Basel, Switzerland) Mar 2017Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in... (Review)
Review
Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in vivo targeting for imaging and therapy. The type II integral membrane protein, prostate specific membrane antigen (PSMA) is overexpressed on prostate cancer cells in proportion to the stage and grade of the tumor progression, especially in androgen-independent, advanced and metastatic disease, rendering it a promising diagnostic and/or therapeutic target. From the perspective of nuclear medicine, PSMA-based radioligands may significantly impact the management of patients who suffer from prostate cancer. For that purpose, chelating-based PSMA-specific ligands have been labeled with various diagnostic and/or therapeutic radiometals for single-photon-emission tomography (SPECT), positron-emission-tomography (PET), radionuclide targeted therapy as well as intraoperative applications. This review focuses on the development and further applications of metal-based PSMA radioligands.
Topics: Ligands; Metals; Phosphoramides; Prostate-Specific Antigen; Radiopharmaceuticals; Urea
PubMed: 28338640
DOI: 10.3390/molecules22040523 -
Australian Journal of General Practice Mar 2023
Topics: Male; Humans; Prostate-Specific Antigen; Decision Making, Shared
PubMed: 36872085
DOI: 10.31128/AJGP-01-23-6692 -
Korean Journal of Radiology 2018The aim of this systematic review was to describe the characteristics of prostate-specific membrane antigen (PSMA)-targeting PET and their clinical applications in... (Review)
Review
The aim of this systematic review was to describe the characteristics of prostate-specific membrane antigen (PSMA)-targeting PET and their clinical applications in prostate cancer patients. There have been major strides in the design, synthesis of PSMA-targeting PET tracers over the past several years. PSMA-targeting PET tracers can be categorized, according to positron emitters and targeting strategies for the PSMA. The majority of PSMA PET studies has been focused on patients with biochemical recurrence, but additional values of PSMA PET have also been investigated for use in primary staging, treatment planning, response evaluation, and PSMA radioligand therapy. PSMA PET is expected to bring improvements in the management of patients, but the impact of improved diagnosis by PSMA on overall survival remains unanswered. Many challenges still await PSMA PET to expedite the use in the clinical practice. At this early stage, prospective multicenter trials are needed to validate the effectiveness and usefulness of PSMA PET.
Topics: Antibodies, Monoclonal; Choline; Contrast Media; Humans; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 30174470
DOI: 10.3348/kjr.2018.19.5.819 -
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 -
Urology Apr 2016
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Male; Prostate-Specific Antigen
PubMed: 27036677
DOI: 10.1016/j.urology.2015.11.047 -
Archives of Pathology & Laboratory... Sep 2019
Topics: Factor V; Hepatitis A; Humans; Male; Prostate-Specific Antigen; Thrombophilia
PubMed: 31453732
DOI: 10.5858/arpa.2019-0222-LE -
International Braz J Urol : Official... 2021
Topics: Humans; Male; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33861056
DOI: 10.1590/S1677-5538.IBJU.2020.0997