Dataset Information

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

ABSTRACT:

Objective

Androgen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.

Subjects and methods

This was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.

Results

After a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41-9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47-13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46-11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18-8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT.

Conclusions

Fracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.

SUBMITTER: Lee CH

PROVIDER: S-EPMC5291449 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

Lee Chi-Ho CH Huang Gang G Chan Pak-Hei PH Hai Jojo J Yeung Chun-Yip CY Fong Carol Ho-Yi CH Woo Yu-Cho YC Ho Kwan Lun KL Yiu Ming-Kwong MK Leung Frankie F Lau Tak-Wing TW Tse Hung-Fat HF Lam Karen Siu-Ling KS Siu Chung-Wah CW

PloS one 20170203 2

<h4>Objective</h4>Androgen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.<h4>Subjects and methods</h4>This was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.<h4>Results</h4>After a ...[more]

PMID: 28158241

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Project description:Background: Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown. Objectives: To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites. Methods: The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence. Results: Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26-1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29-1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization. Conclusion: Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.

Project description:Background. For men with intermediate-risk prostate cancer (IRPC), adding short-term androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) has shown efficacy, but men are often reluctant to accept it because of its impact on quality of life. Methods. We conducted time tradeoffs (score of 1 = perfect health and 0 = death) and probability tradeoffs with patients aged 51 to 78 y who had received EBRT for IRPC within the past 2 y. Of 40 patients, 20 had received 6 mo of ADT and 20 had declined. Utility assessments explored 4 ADT-related side effects: hot flashes, fatigue, loss of libido/erectile dysfunction, and weight gain. Results. The most commonly reported "worst" treatment-related complication of ADT was fatigue (50% in both cohorts) followed by reduced libido/erectile dysfunction (40% in both cohorts). The utilities for fatigue were mean = 0.71 and median = 0.92 and for reduced libido/erectile dysfunction were mean = 0.81 and median = 0.92. Utilities did not differ significantly between cohorts. Assuming a 6-mo course of ADT, men reported being willing to trade 3 mo of life expectancy to avoid fatigue due to ADT and 1.8 mo to avoid sexual side effects. Patients in the ADT cohort were willing to accept the side effects of ADT in exchange for a mean 8% absolute increase in survival, whereas patients in the no ADT cohort required a 16% increase (P < 0.001). Conclusions. When considering treatment with ADT, men with IRPC identified fatigue and sexual dysfunction as the most bothersome side effects. Patients who declined ADT expected a larger survival benefit than those who opted for treatment. Both groups expected a survival benefit exceeding that shown by recent trials, suggesting some men may be selecting treatments inconsistent with their preferences.HighlightsThis study demonstrates that prostate cancer patients receiving radiation therapy are reluctant to receive androgen deprivation therapy (ADT) most commonly due to anticipated fatigue and loss of libido/erectile dysfunction.Men who had received ADT reported they would require an average 8% absolute increase in survival to tolerate its side effects, whereas those who declined ADT would require an average 16% increase.Required thresholds are well above the estimated absolute survival benefit for ADT demonstrated in recent clinical trials, suggesting an unmet need for improved patient education regarding the risks and benefits of ADT.

Project description:PurposeAndrogen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors.Materials and methodsWe conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses.ResultsDiabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008).ConclusionsPrimary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.

Project description:PurposeExcess fat mass (FM) contributes to poor prostate cancer (PCa) prognosis and comorbidity. However, FM gain is a common side effect of androgen deprivation therapy (ADT). We examined the efficacy of a 12-wk weight loss intervention to reduce FM and maintain lean mass (LM) in ADT-treated obese PCa patients.MethodsFourteen ADT-treated obese PCa patients (72 ± 9 yr, 39.7% ± 5.4% body fat) were recruited for a self-controlled prospective study, with 11 completing the 6-wk control period, followed by a 12-wk intervention comprising 300 min·wk-1 of exercise including supervised resistance training and home-based aerobic exercise, and dietitian consultations advising a daily energy deficit (2100-4200 kJ) and protein supplementation. Body composition was assessed by dual x-ray absorptiometry. Secondary outcomes included muscle strength (one-repetition maximum), cardiorespiratory fitness (maximal oxygen consumption), and blood biomarkers.ResultsThere were no significant changes during the control period. Patients attended 89% of supervised exercise sessions and 100% of dietitian consultations. No changes in physical activity or energy intake were observed. During the intervention, patients experienced significant reductions in weight (-2.8 ± 3.2 kg, P = 0.016), FM (-2.8 ± 2.6 kg, P < 0.001), and trunk FM (-1.8 ± 1.4 kg, P < 0.001), with LM preserved (-0.05 ± 1.6 kg, P = 0.805). Muscle strength (4.6%-24.7%, P < 0.010) and maximal oxygen consumption (3.5 ± 4.7 mL·min-1·kg-1, P = 0.041) significantly improved. Leptin significantly decreased (-2.2 (-2.7 to 0.5) ng·mL-1, P = 0.016) with no other changes in blood biomarkers such as testosterone and lipids (P = 0.051-0.765); however, C-reactive protein (rs = -0.670, P = 0.024) and triglycerides (r = -0.667, P = 0.025) were associated with individual changes in LM.ConclusionsThis study shows preliminary efficacy for an exercise and nutrition weight loss intervention to reduce FM, maintain LM, and improve muscle strength and cardiorespiratory fitness in ADT-treated obese PCa patients. The change in body composition may affect blood biomarkers associated with obesity and PCa progression; however, further research is required.

Dataset Information

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

Objective

Subjects and methods

Results

Conclusions

Publications

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma.

Similar Datasets

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