The relationship between PTEN mutations and resistance to androgen-deprivation therapy in prostate cancer

AbstractOver the past 60 years, androgen deprivation therapy has been the mainstay of treatment of metastatic prostate cancer. However, research findings suggest that androgen deprivation therapy inflicts serious adverse effects on overall health and reduces the quality of life. Among the adverse effects known to date are insulin resistance, diabetes, metabolic syndrome fatigue, erectile dysfunction, and cardiovascular disease. In this clinical perspective, we discuss the relationship between induced androgen deficiency and a host of pathologies in the course of treatment with androgen deprivation therapy for prostate cancer patients.

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Influence of age on incident diabetes (DM) and cardiovascular disease (CVD) among prostate cancer survivors receiving androgen deprivation therapy (ADT).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.31 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 31-31

Author(s):

Alicia Katherine Morgans ◽

Kang-Hsien Fan ◽

Tatsuki Koyama ◽

Peter C. Albertsen ◽

Michael Goodman ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Cancer Survivors ◽

Androgen Deprivation Therapy ◽

Older Men ◽

Androgen Deprivation ◽

Age At Diagnosis ◽

Prostate Cancer Survivors ◽

Increased Risk ◽

The Relationship

31 Background: Androgen deprivation therapy (ADT) has been associated with an increased risk of developing diabetes (DM) and cardiovascular disease (CVD), though this is controversial, particularly for CVD. We prospectively assessed the relationship between ADT and incident DM and CVD in the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. Methods: We identified men in the PCOS with non-metastatic prostate cancer diagnosed from 1994 to 1995 and followed through 2009 to 2010. We used multivariable logistic regression models to compare groups receiving short-term ADT (less than 2 years), prolonged ADT (2 years or more) and no ADT to assess the relationship between ADT exposure and subsequent diagnoses of DM and CVD (determined by patient report and cause of death data). We evaluated the effects of age at diagnosis, race, stage, and comorbidity on the development of DM and CVD. Results: Among 3,526 men with comorbidity and treatment data, 2,985 men without baseline DM and 3,112 men without baseline CVD constituted the DM and CVD cohorts, respectively. Regardless of duration of ADT exposure, there was not an increased risk of DM or CVD in men younger than 70 at diagnosis. Compared to no ADT exposure, prolonged ADT was associated with an increased risk of DM and CVD that increased steadily over age 76 at diagnosis for DM (OR 2.11 at age 74, 95% CI 1.02 – 4.36; OR 2.65 at age 80, 95% CI 1.09 – 6.47) and age 74 at diagnosis for CVD (OR 1.89 at age 74, 95% CI 1.02 - 3.49; OR 3.19 at age 80, 95% 1.25 – 8.17). Increasing comorbidity burden modified risk of DM and CVD (for 3 or more comorbidities vs. no comorbidities; for DM, OR 4.25, 95% CI 2.3 - 7.9; and for CVD, OR 8.1, 95% CI 4.3 -15.5 P<0.001). Conclusions: The relationship between ADT and development of CVD and DM may be dependent upon age at diagnosis in addition to length of ADT administration, with longer ADT exposure predominantly increasing risk among older men only. Men with greater comorbid burden had increased risk of developing DM and CVD. Closer monitoring for development of DM and CVD may be most important among older men receiving prolonged ADT, especially those with other comorbidities.

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The influence of an androgen deprivation therapy educational program on dyadic quality and intimacy for prostate cancer patients and their partners.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.7_suppl.178 ◽

2018 ◽

Vol 36 (7_suppl) ◽

pp. 178-178

Author(s):

Erik Wibowo ◽

Richard J Wassersug ◽

John W Robinson ◽

Andrew Matthew ◽

Deborah L McLeod ◽

...

Keyword(s):

Prostate Cancer ◽

Side Effects ◽

Physical Exercise ◽

Androgen Deprivation Therapy ◽

Educational Program ◽

Androgen Deprivation ◽

Dyadic Adjustment ◽

Dyadic Relationship ◽

Relationship Duration ◽

The Relationship

178 Background: Androgen deprivation therapy (ADT) is a common treatment for advanced prostate cancer (PCa), but ADT typically impairs men’s sexual function and couples’ relationships. We offer an educational program to help PCa patients and their partners manage ADT related side effects and to maintain a strong dyadic relationship while the patient is on ADT. Methods: Patients and partners attended a one time 1.5 hour ADT Class. Patients received a copy of the book Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (DEMOS Health, NY), which covers how to manage ADT side effects and make healthy lifestyle changes. We emphasize the importance of physical exercise in preventing or reducing many of the side effects of ADT. 79 couples (patients = 68.8±7.5 years old, partners = 64.9±8.8 years old; relationship duration = 34.6±16.4 years) completed the Dyadic Adjustment Scale, the Personal Assessment of Intimacy in Relationships, and the Godin Leisure-Time Exercise questionnaires at baseline and again 2-3 months later to assess their relational intimacy and dyadic quality. At baseline 73% of patients either had not started or been on ADT for < 3 weeks. Results: Attending the ADT Educational Program was associated with improved dyadic adjustment and relational intimacy but age, relationship duration, baseline strain in the relationship and physical exercise all influence these effects. Specifically, dyadic cohesion improved in patients ≥68 years old. Recreational intimacy increased in patients ≤60 years old and for those in a relationship ≥50 years. Recreational intimacy also improved in partners who had been in a 20-49 years relationship or those reporting at baseline little strain in their relationship. Dyadic cohesion was maintained in participants who increased their frequency of physical exercise. For the above results, all P < 0.05. Conclusions: The ADT Educational Program improves dyadic cohesion and relational intimacy for some patients and partners but age, relationship duration, baseline quality of the relationship, and physical exercise frequency appear to influence the effectiveness of the program.

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A 2‐year prospective analysis of insomnia as a mediator of the relationship between androgen deprivation therapy and perceived cognitive function in men with prostate cancer

Cancer ◽

10.1002/cncr.33850 ◽

2021 ◽

Author(s):

Sheila N. Garland ◽

Josée Savard ◽

Sarah L. Eisel ◽

Richard J. Wassersug ◽

Nicholas J. Rockwood ◽

...

Keyword(s):

Prostate Cancer ◽

Cognitive Function ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Prospective Analysis ◽

Perceived Cognitive Function ◽

The Relationship

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Prostate cancer treatment and the relationship of androgen deprivation therapy to cognitive function

Clinical & Translational Oncology ◽

10.1007/s12094-021-02727-1 ◽

2021 ◽

Author(s):

A. B. Reiss ◽

U. Saeedullah ◽

D. J. Grossfeld ◽

A. D. Glass ◽

A. Pinkhasov ◽

...

Keyword(s):

Prostate Cancer ◽

Cognitive Function ◽

Cancer Treatment ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Prostate Cancer Treatment ◽

Relationship Of ◽

The Relationship

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On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2

Annals of Oncology ◽

10.1016/j.annonc.2020.06.005 ◽

2020 ◽

Vol 31 (10) ◽

pp. 1415-1416 ◽

Cited By ~ 5

Author(s):

O. Caffo ◽

V. Zagonel ◽

C. Baldessari ◽

A. Berruti ◽

R. Bortolus ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Risk Of Infection ◽

The Relationship

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The relationship between androgen deprivation therapy and depression symptoms in patients with prostate cancer

The Aging Male ◽

10.1080/13685538.2018.1560404 ◽

2019 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Yi-Zhong Chen ◽

Pai-Kai Chiang ◽

Wun-Rong Lin ◽

Marcelo Chen ◽

Yung-Chiong Chow ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Depression Symptoms ◽

The Relationship

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Analysis of Brain Functions in Men with Prostate Cancer under Androgen Deprivation Therapy: A One-Year Longitudinal Study

Life ◽

10.3390/life11030227 ◽

2021 ◽

Vol 11 (3) ◽

pp. 227

Author(s):

Vanessa Sánchez-Martínez ◽

Cristina Buigues ◽

Rut Navarro-Martínez ◽

Laura García-Villodre ◽

Noura Jeghalef ◽

...

Keyword(s):

Prostate Cancer ◽

Depressive Symptoms ◽

Luteinizing Hormone ◽

Sleep Quality ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Luteinizing Hormone Releasing Hormone ◽

Releasing Hormone ◽

One Year ◽

The Relationship

The relationship between cognitive decline and androgen deprivation therapy (ADT) under luteinizing hormone-releasing hormone (LHRH) analogues is unclear, and there is a scarcity of longitudinal studies considering the interaction between cognition, depressive symptoms and sleep quality in men with prostate cancer (PCa) treated with ADT. This study aimed to determine if there were differences in the scores obtained in cognitive assessment, depressive symptoms, and sleep quality after one year of ADT and determine the interrelations between sleep, mood, and cognitive status. A prospective longitudinal observational study was designed, in which a cohort of men (mean age was 70.8 years) newly treated with androgen-deprivation therapy was assessed in the first six months of treatment and 12 months later. Analysis of cognitive function by the Mini-Mental State Examination (MMSE) scores indicated a significant (p < 0.05) increase after one year of treatment and by the Brief Scale for Cognitive Evaluation (BCog) scores indicated no changes in the scores before and after one year of treatment. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p < 0.05) changes after one year of treatment with ADT, with men describing more depressive symptoms and more sleep disturbances. No statistically significant differences were found in the cognitive performance between men with impaired sleep or depression results and those without them. Our study showed no clinical evidence of the relationship between ADT under luteinizing hormone-releasing hormone (LHRH) analogues and cognitive deterioration in 1-year follow-up, but there are impairments in the sleep quality in men with PCa undergoing ADT and an increase in depressive symptoms which has important implications for clinicians as they would impair quality of life and adherence to treatment.

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Is Androgen Deprivation Therapy for Prostate Cancer Associated with Cardiovascular disease ? A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v1 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Longlong Chen ◽

Yawei Xu ◽

Yongjiao Yang ◽

Rui Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Disease Risk ◽

Meta Analysis ◽

Androgen Deprivation ◽

Increased Risk ◽

Significant Difference ◽

The Relationship

Abstract Background: Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular related disease is poorly defined. The aim of the present meta‐analysis is to explore the relationship between ADT and the risk of cardiovascular disease (CVD). Method: For this systematic review and meta-analysis, we searched databases until April 2019 for randomized controlled trial (RCT) or observational studies that reported data on ADT administration and cardiovascular disease (CVD) incidence. The relationship was evaluated through estimate relative risk ratio (RR) and 95% confidence intervals (CIs) Result: A statistically significant difference was detected for acute myocardial infarction (AMI) (RR = 1.13; 95% CI, 1.10–1.15; P< 0.05) including a total of 142,186 cases and 174,404 controls. Significant difference between coronary heart disease (CHD) and ADT was also observed, with summary (RR=1.11; 95% confidence interval CI: 1.10-1.13), from 157,339 ADT users and 349,636 non-ADT users of 7 eligible studies. Conclusions: Pooled result demonstrated that ADT could significantly increase the risk of CHD, AMI and sudden cardiac death (SCD). Various ADT modalities have different impact on cardiovascular disease risk in different level. Our meta-analysis also suggests that the application of ADT in prostate cancer patients for over 5 years resulted in a significant increase in cardiovascular morbidity. Moreover, subgroup analyses for different types of ADT indicated that compared with the individual administration of ADT, GnRH plus AA (oral anti-androgens) is more likely significantly lead to AMI.

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