A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Purpose To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. Patients and Methods: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. Results At 2 years, 33% of patients had developed bone metastases. Median bone metastasis–free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. Conclusion Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.

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Prostate-selective α antagonists increase fracture risk in prostate cancer patients with and without a history of androgen deprivation therapy: a nationwide population-based study

Oncotarget ◽

10.18632/oncotarget.23828 ◽

2018 ◽

Vol 9 (4) ◽

pp. 5263-5273

Author(s):

Wei-Heng Kao ◽

Chang-Fu Kuo ◽

I-Jun Chou ◽

Lai-Chu See ◽

Wen-Kuan Huang ◽

...

Keyword(s):

Prostate Cancer ◽

Fracture Risk ◽

Cancer Patients ◽

Androgen Deprivation Therapy ◽

Population Based ◽

Androgen Deprivation ◽

Population Based Study ◽

Increase Fracture Risk ◽

History Of

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Identifying men at greatest risk of weight gain from androgen deprivation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.80 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 80-80

Author(s):

Daniel Martin Seible ◽

Xiangmei Gu ◽

Andrew Hyatt ◽

Clair Beard ◽

Jason Alexander Efstathiou ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Weight Gain ◽

Androgen Deprivation Therapy ◽

Weight Change ◽

Androgen Deprivation ◽

Baseline Risk ◽

Diabetic Patients ◽

Diabetic Status ◽

One Year

80 Background: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer therapy. Weight gain is among the adverse metabolic changes associated with ADT, and may contribute to cardiovascular comorbidity. A better understanding of the risk factors for weight gain on ADT is important for optimal management of ADT-associated morbidity. Methods: A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT. The primary endpoint was weight change at one year from ADT initiation, with the secondary aim to stratify risk of weight gain by baseline patient characteristics. Statistical analyses were performed using two-tailed t-tests and linear regression. Results: Men in our cohort exhibited a significant increase in weight (p=0.0005) in the one year following ADT initiation. Three risk factors for weight gain on ADT were identified: younger than age 65 (5.98 pounds gained, p=0.001 vs. 1.63 pounds, p= 0.09 for age 65+), body mass index (BMI) less than 30 (4.36 pounds gained, p=0.00002 vs. 0.22 pounds, p=0.87 for BMI 30+), and non-diabetic status (3.43 pounds gained, p=0.0003 vs. 0.57 pounds, p=0.74 for diabetics). An aggregate risk scoring system was contrived to allow for weight change prediction by total number of risk factors present: scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -2.42 (p=0.43), +0.9 (p=0.56), +2.9 (p=0.01) and +8.3 pounds (p= 0.0001) respectively. Weight gain increased significantly with increasing risk score (p-trend= 0.0005), decreasing baseline age (p-trend= 0.004) and decreasing baseline BMI (p-trend= 0.01). Conclusions: Younger than age 65, BMI less than 30, and non-diabetic status were each significantly associated with weight gain one year after starting ADT. Increasing weight gain was strongly associated with increasing number of baseline risk factors. Although metabolic consequences were previously considered most significant for patients with preexisting comorbidity, these data suggest younger, slimmer, and non-diabetic patients may be at higher risk for gaining weight on ADT. As these three categories of men generally have higher endogenous testosterone (T) levels prior to ADT compared to older, obese, and diabetic men, the magnitude of T decline following ADT might explain these findings.

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Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable intermediate- and high-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.41 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 41-41

Author(s):

Michael A Dyer ◽

Ming-Hui Chen ◽

Michelle H. Braccioforte ◽

Brian Joseph Moran ◽

Anthony V. D'Amico

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

External Beam Radiation ◽

Intermediate Risk ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer ◽

History Of ◽

Over Time

41 Background: Despite evidence of prolonged survival when adding androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) in men with unfavorable intermediate- and high-risk prostate cancer (PC), some of these men are not receiving ADT. We explored whether comorbidity can explain this discrepancy given the observation that survival may be shortened in men with moderate to severe comorbidity who receive ADT. Methods: Between 10/1997 and 5/2013, 3,348 men with unfavorable intermediate- (2,380 patients; 70.7%) or high-risk (986 patients; 29.3%) PC were treated at the Prostate Cancer Foundation of Chicago using brachytherapy with or without neoadjuvant EBRT and/or ADT, and formed the study cohort. A multivariable logistic regression analysis was used to evaluate whether comorbidity (history of congestive heart failure [CHF] and/or myocardial infarction [MI]) was associated with decreased odds of ADT use in men with unfavorable intermediate- or high-risk PC, adjusting for age, PC prognostic factors, year of brachytherapy, and EBRT use. Results: Among patients with unfavorable-intermediate-risk PC, 31.2% received ADT, and in the high-risk cohort, 38.3%, 12.3%, and 4.8% received up to 6, >6-18, or >18 months of ADT respectively. In men with high-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use of any duration (all p values >0.71), but the odds of ADT use decreased over time (adjusted odds ratio (AOR) 0.87, 95% confidence interval (CI) [0.83,0.91], p<0.0001; AOR 0.93, 95% CI [0.87,0.99], p=0.023; AOR 0.92, 95% CI [0.83,1.01], p=0.089, for up to 6, >6-18, and >18 months respectively, with no ADT as the reference). Similarly, in men with unfavorable intermediate-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use (p=0.49), whereas the odds of ADT use decreased significantly over time (AOR 0.96, 95% CI [0.94,0.98], p=0.0009). Conclusions: While ADT use has decreased over time in men with unfavorable intermediate- and high-risk PC undergoing brachytherapy with or without supplemental EBRT, this decrease does not appear to be occurring in men with a history of CHF or MI.

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Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy

Cancer ◽

10.1002/cncr.20388 ◽

2004 ◽

Vol 101 (3) ◽

pp. 541-549 ◽

Cited By ~ 78

Author(s):

Tracey L. Krupski ◽

Matthew R. Smith ◽

Won Chan Lee ◽

Chris L. Pashos ◽

Jane Brandman ◽

...

Keyword(s):

Natural History ◽

Androgen Deprivation Therapy ◽

Prostate Carcinoma ◽

Androgen Deprivation ◽

History Of ◽

Bone Complications

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Evidence for reduced neuromuscular function in men with a history of androgen deprivation therapy for prostate cancer

Clinical Physiology and Functional Imaging ◽

10.1111/cpf.12084 ◽

2013 ◽

Vol 34 (3) ◽

pp. 209-217 ◽

Cited By ~ 7

Author(s):

Danielle Girard ◽

Frank E. Marino ◽

Jack Cannon

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Neuromuscular Function ◽

Androgen Deprivation ◽

History Of

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Risk of Cardiovascular Ischemic Events After Surgical Castration and Gonadotropin-Releasing Hormone Agonist Therapy for Prostate Cancer: A Nationwide Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.71.4204 ◽

2017 ◽

Vol 35 (32) ◽

pp. 3697-3705 ◽

Cited By ~ 18

Author(s):

Dong-Yi Chen ◽

Lai-Chu See ◽

Jia-Rou Liu ◽

Cheng-Keng Chuang ◽

See-Tong Pang ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Gonadotropin Releasing Hormone ◽

Androgen Deprivation ◽

Releasing Hormone ◽

Gonadotropin Releasing Hormone Agonist ◽

Bilateral Orchiectomy ◽

History Of ◽

Ischemic Events

Purpose Our aim was to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive androgen-deprivation therapy by surgical castration and those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy. Patients and Methods By using the Taiwan National Health Insurance Research Database, we analyzed data from 14,715 patients with PCa diagnosed from January 1, 1997, through December 31, 2011. The patients were treated with bilateral orchiectomy or GnRHa therapy. We used inverse probability of treatment weighting with propensity scores to adjust for the imbalance in covariate baseline values between these two groups. Cox regression models were used to identify risk factors for myocardial infarction (MI), ischemic stroke (IS), and cardiac-related complications. Results Overall, 3,578 patients with PCa (24.3%) underwent bilateral orchiectomy and 11,137 patients (75.7%) received GnRHa therapy. Both groups had a similar risk of CV ischemic events (ie, MI or IS; hazard ratio, 1.16; 95% CI, 0.97 to 1.38) during a median follow-up time of 3.3 years. However, during the first 1.5 years of follow-up, there were higher CV ischemic events in the orchiectomy group than in the GnRHa group (hazard ratio, 1.40; 95% CI, 1.04 to 1.88), particularly in patients who were ≥ 65 years of age, had hypertension, had a Charlson comorbidity index score ≥ 3, and had a previous history of MI, IS, or coronary heart disease. Conclusion Compared with bilateral orchiectomy, use of GnRHa does not increase the risk of CV ischemic events in patients with PCa. Nonetheless, orchiectomy is associated with higher rates of CV ischemic events in older patients and those with a history of CV comorbidities within 1.5 years of initiating androgen-deprivation therapy. These findings can help clinicians decide on the optimal castration strategy for individual patients.

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