Continuous androgen-deprivation therapy increased risk for diabetes and fragility fractures in older men with prostate cancer

2009 ◽  
Vol 151 (12) ◽  
pp. JC6 ◽  
Author(s):  
Julio Hajdenberg
2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 31-31
Author(s):  
Alicia Katherine Morgans ◽  
Kang-Hsien Fan ◽  
Tatsuki Koyama ◽  
Peter C. Albertsen ◽  
Michael Goodman ◽  
...  

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.


2009 ◽  
Vol 27 (21) ◽  
pp. 3452-3458 ◽  
Author(s):  
Shabbir M.H. Alibhai ◽  
Minh Duong-Hua ◽  
Rinku Sutradhar ◽  
Neil E. Fleshner ◽  
Padraig Warde ◽  
...  

Purpose Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. Methods Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. Conclusion Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.


2007 ◽  
Vol 177 (4S) ◽  
pp. 200-200 ◽  
Author(s):  
Andrea Gallina ◽  
Pierre I. Karakiewicz ◽  
Jochen Walz ◽  
Claudio Jeldres ◽  
Quoc-Dien Trinh ◽  
...  

2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario

Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.


2018 ◽  
Vol 36 (5) ◽  
pp. 241.e1-241.e6
Author(s):  
Christopher J.D. Wallis ◽  
Raj Satkunasivam ◽  
Sender Herschorn ◽  
Calvin Law ◽  
Arun Seth ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16510-e16510
Author(s):  
Elizabeth Riley Kessler ◽  
Thomas W. Flaig ◽  
Elaine Tat Lam ◽  
Kathryn M. Breaker ◽  
Michael Wacker ◽  
...  

e16510 Background: Alteration of the androgen axis through androgen deprivation therapy (ADT) is the mainstay of prostate cancer (PCa) treatment. Unfortunately, the resultant hypogonadal state has detrimental effects on muscle and bone and may impair physical function (PF). Older patients may be more vulnerable to PF changes while on ADT. We conducted a pilot study to evaluate the changes in PF and geriatric health in older men initiating ADT using tests easily employed in routine clinical practice. Methods: Men with PCa initiating ADT were enrolled and were assessed every 3 months (mos) for up to 12 mos. PF was measured using the short physical performance battery (SPPB) and geriatric health was screened using the Vulnerable Elders Survey (VES13) which predicts potential death or decline over 2 years. The primary endpoint was change in SPPB and VES13 at 3 mos. Results: We enrolled 17 patients with a median age of 75 years (range 67-85) beginning ADT therapy. Fourteen patients had metastasis, 2 had locally advanced disease, and 1 had biochemical recurrence. The majority had Gleason score (GS) 7 cancer (9/17), 7/17 GS 8-10, and 1/17 with GS 6. Eight patients had normal SPPB baseline scores and 9 had moderate impairment (moderate frailty risk) (Mean 10, SD 1.71). Seven had a clinically significant decline in the SPPB at 3 mos, with 1 patient testing as severely impaired. The VES13 screening tool identified 6/17 patients as vulnerable at baseline (Mean 3, SD 3.92). At 3 months, 3/17 patients had a decline in VES13 and 6/17 with an improvement. Of the 10 patients who were followed for at least 6 months, 5 had worsening of the VES13 and 2 had a worsening in SPPB. Conclusions: Older patients initiating ADT have baseline vulnerabilities in geriatric health with little immediate detriment after treatment initiation, perhaps due to overall health improvement with treatment initiation. Changes in PF, however, are seen within the first 3 months of ADT in nearly half of our patients, warranting further investigation into early rehabilitation of men even on short-term ADT. The SPPB is easily employed in clinic and important as reliance on VES13 alone is likely to miss patients with PF impairments.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 207-207
Author(s):  
Daniel M. Lim ◽  
Roman Gulati ◽  
Serge Aleshin-Guendel ◽  
Heather H. Cheng ◽  
Agnes M. Gawne ◽  
...  

207 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate specific antigen (PSA) levels as a marker of efficacy. The proportion of patients and clinical relevance of those with a prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥ 0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death from any cause were evaluated by log-rank tests. Results: After ineligibility exclusions, data were abstracted from 93 patients. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were n=23/93 (24.7%; 95% CI 16.4–34.8%; P<0.001) and n=14/93 (15.1%; 95% CI 8.5–24.0%; P<0.001), respectively. Proportions of patients with undetectable PSA 12 and 24 months after testosterone recovery ≥ 50 ng/dL were n=16/65 (24.6%; 95% CI 14.8-36.9%) and n=10/65 (15.4%; 95% CI 7.6-26.5%), respectively. Being 1 year older at diagnosis was associated with an 11.5% (95% CI 3.1–21.9%; P=0.01) increase in the odds of having a detectable PSA after controlling for PSA at diagnosis, Gleason sum and time from initial therapy to BCR. Detectable PSA was associated with increased risk of metastasis (P=0.006) with marginal evidence of association with death from any cause (P=0.07). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. Additional analysis is needed to demonstrate the clinical value of this measure as a surrogate for prostate cancer outcomes and for consideration as a trial endpoint.


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