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Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

ABSTRACT: Prostate cancer (PC) is one of the most common malignancies in men. The increase in the number of PC survivors is associated with many problems including cognitive impairment. Early detection of such problems facilitates timely protective intervention. This study examined the association between prostate-specific antigen (PSA) or testosterone (T) levels and cognitive function in patients undergoing radical prostatectomy. Such a correlation could help identify patient groups at risk of cognitive impairment. Participants underwent clinical (demographic data, medical history, physical examination, and blood analyses) and neuropsychological assessment (cognitive test battery). Preoperative PSA or T levels were not associated with cognitive function. However, long-term follow-up after prostatectomy showed a strong correlation between PSA levels and the results of verbal memory and executive function tests. A trend toward significance was also observed for visuospatial memory. The levels of free T and total T were not correlated with cognitive function. Only the levels of free T after hormonal treatment were significantly correlated with executive functions. Comorbid diabetes affected these correlations. In conclusion, PSA levels at a distant postoperative time and free T level after hormonal treatment may be biomarkers of cognitive function.

SUBMITTER: Popiolek A

PROVIDER: S-EPMC8619514 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

Popiołek Alicja A Brzoszczyk Bartosz B Jarzemski Piotr P Chyrek-Tomaszewska Aleksandra A Wieczór Radosław R Borkowska Alina A Bieliński Maciej M

Journal of clinical medicine 20211115 22

Prostate cancer (PC) is one of the most common malignancies in men. The increase in the number of PC survivors is associated with many problems including cognitive impairment. Early detection of such problems facilitates timely protective intervention. This study examined the association between prostate-specific antigen (PSA) or testosterone (T) levels and cognitive function in patients undergoing radical prostatectomy. Such a correlation could help identify patient groups at risk of cognitive ...[more]

PMID: 34830590

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Project description:BackgroundMost men diagnosed with prostate cancer today have organ-confined disease and low risk of disease recurrence after radical prostatectomy. Testosterone deficiency in prostate cancer survivors contributes to impaired health-related quality of life but testosterone treatment is viewed as a contraindication in this population.ObjectivesWe describe the design of the first randomized trial to determine the safety and efficacy of testosterone treatment in men who have undergone prostatectomy for non-aggressive prostate cancer and have symptomatic testosterone deficiency.MethodsSurviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial is a randomized, placebo-controlled, double-blind, parallel group trial in 142 men, ≥ 40 years, who have undergone radical prostatectomy for organ-confined prostate cancer, Gleason score ≤ 7 (3+4), Stage pT2, N0, M0 lesions and have symptomatic testosterone deficiency and undetectable prostate specific antigen for > 2 years after surgery. Eligible participants are randomized to weekly intramuscular injections of 100-mg testosterone cypionate or placebo for 12 weeks and followed for another 12 weeks. Primary endpoint is change from baseline in sexual activity. Secondary outcomes include change in sexual desire, erectile function, energy, lean and fat mass, physical and cognitive performance. Safety is assessed by monitoring prostate-specific antigen, lower urinary tract symptoms, hemoglobin, and adverse events.ResultsThe trial is being conducted at two trial sites in Boston, MA and Baltimore, MD. As of July 30, 2022, 42 participants have been randomized. No prostate-specific antigen or clinical recurrence has been noted to-date.DiscussionRecruitment was slowed by coronavirus disease 2019-related closures, slow subsequent ramp-up of research activities, and patient concerns about safety of testosterone treatment. Despite these challenges, participant retention has been high.ConclusionThe Surviving Prostate cancer while Improving quality of life through Rehabilitation with Testosterone Trial, a placebo-controlled, randomized trial, will determine whether testosterone replacement therapy is safe and efficacious in correcting symptoms of testosterone deficiency in prostate cancer survivors, and potentially inform clinical practice.

Project description:BackgroundPhysician prescribing patterns surrounding the use of testosterone therapy (TTh) in men with a history of prostate cancer (CaP) is not well described.AimTo characterize the demographics and usage patterns of testosterone therapy in men with a history of prostate cancer in the United States.MethodsThis was a retrospective review using Optum's De-identified Clinformatics Data Mart database. Administrative diagnosis, procedural, pharmacy, and laboratory codes were used to identify male subjects 40 years and older with prostate cancer treated with surgery or radiation between 2003 and 2018 who went on to receive TTh. Demographic and clinical factors are identified. Temporal trends in TTh usage were reported.OutcomesThe main outcomes were rates of testosterone prescriptions in men with treated prostate cancer and associated laboratory values such as Prostate Specific Antigen (PSA) and testosterone levels before TTh.Results126,374 men completed treatment for CaP during the study period (42,515 surgery, 75,186 radiation, 8,673 both). Of these, 3,074 men (2.4%) received testosterone after CaP treatment. Men who received testosterone were younger, more likely to have erectile dysfunction, depressive disorder, and lower pretreatment PSA values compared to men who did not receive. Median PSA levels before TTh initiation were 0 - 0.2 depending on CaP treatment modality and median total testosterone level was <300 ng/dL. TTh began an average of 1.5 years after radical prostatectomy and 2.6 years after radiation treatment. We observed an increase in TTh after CaP from the beginning of the study period until it peaked in 2013 at 4.9%. After 2013, rates decreased annually until a plateau of approximately 1.8% of men. Approximately a third of men did not have testosterone labs checked before initiation of TTh.Clinical implicationsThese findings provide insight into trends in testosterone prescriptions in men after prostate cancer treatment and may aid in clinical decision-making, as well as areas for improvement in cancer survivorship care.Strengths and limitationsStrengths include the large sample size, length of data coverage, and real-world analysis of testosterone prescribing patterns across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact decision making regarding TTh.ConclusionNational trends in testosterone prescriptions for men with treated prostate cancer suggest that many men are treated with TTh after prostate cancer therapy with patterns of indications and monitoring consistent with the general population. Chen T, Li S, Eisenberg M. Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States. J Sex Med 2021;18:1346-1353.

Project description:Prostate-specific membrane antigen (PSMA) remains an important target for diagnostic and therapeutic application for human prostate cancer. Model cell lines have been recently developed to study canine prostate cancer but their PSMA expression and enzymatic activity have not been elucidated. The present study was focused on determining PSMA expression in these model canine cell lines and the use of fluorescent small-molecule enzyme inhibitors to detect canine PSMA expression by flow cytometry.Western blot and RT-PCR were used to determine the transcriptional and translational expression of PSMA on the canine cell lines Leo and Ace-1. An endpoint HPLC-based assay was used to monitor the enzymatic activity of canine PSMA and the potency of enzyme inhibitors. Flow cytometry was used to detect the PSMA expressed on Leo and Ace-1 cells using a fluorescently tagged PSMA enzyme inhibitor.Canine PSMA expression on the Leo cell line was confirmed by Western blot and RT-PCR, the enzyme activity, and flow cytometry. Kinetic parameters Km and Vmax of PSMA enzymatic activity for the synthetic substrate (PABG?G) were determined to be 393?nM and 220?pmol?min(-1) ?mg?protein(-1) , respectively. The inhibitor core 1 and fluorescent inhibitor 2 were found to be potent reversible inhibitors (IC50 ?=?13.2 and 1.6?nM, respectively) of PSMA expressed on the Leo cell line. Fluorescent labeling of Leo cells demonstrated that the fluorescent PSMA inhibitor 2 can be used for the detection of PSMA-positive canine prostate tumor cells. Expression of PSMA on Ace-1 was low and not detectable by flow cytometry.The results described herein have demonstrated that PSMA is expressed on canine prostate tumor cells and exhibits similar enzymatic characteristics as human PSMA. The findings show that the small molecule enzyme inhibitors currently being studied for use in diagnosis and therapy of human prostate cancer can also be extended to include canine prostate cancer. Importantly, the findings demonstrate that the potential of the inhibitors for use in diagnosis and therapy can be evaluated in an immunocompetent animal model that naturally develops prostate cancer before use in humans.

Dataset Information

Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

Publications

Prostate-Specific Antigen and Testosterone Levels as Biochemical Indicators of Cognitive Function in Prostate Cancer Survivors and the Role of Diabetes.

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