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ABSTRACT: BACKGROUND: Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown. OBJECTIVE: To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage <T3); and 1360 men with localized or locally advanced, high-risk PCa consecutively treated in a community-based, multi-institutional setting between 1991 and 2006. CAD risk factors included at least a history of diabetes mellitus, hypercholesterolemia, or hypertension. The median follow-up for men with low-, intermediate-, and high-risk PCa were 4.1, 4.4, and 4.6 yr, respectively. INTERVENTIONS: Men were treated with or without a median duration of 4 mo of NHT followed by brachytherapy with or without supplemental external-beam radiation therapy (EBRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression multivariable analyses were performed to assess whether NHT use affected the risk of ACM in men with low-, intermediate-, and high-risk PCa, adjusting for age; year of brachytherapy; supplemental EBRT use; the presence of CAD risk factors; treatment propensity score; and known PCa prognostic factors, including pretreatment PSA level, biopsy Gleason score, and clinical stage. RESULTS AND LIMITATIONS: NHT use was associated with a significantly increased risk of ACM in men with low-risk PCa (adjusted hazard ratio [HR]: 1.27; 95% confidence interval [CI], 1.07-1.51; p<0.01) but not in men with intermediate-risk (adjusted HR: 1.13; 95% CI, 0.96-1.35; p=0.15) or high-risk PCa (adjusted HR: 0.86; 95% CI, 0.66-1.13; p=0.28). Using an interaction model for the low-risk group, NHT use was associated with a significantly increased risk of ACM in the subgroup of men with at least a single CAD risk factor (adjusted HR: 1.36; 95% CI, 1.07-1.74; p=0.01) but not for men with no CAD risk factors (adjusted HR: 1.19; 95% CI, 0.95-1.51; p=0.13). CONCLUSIONS: For men with no or at least a single risk factor for CAD, NHT use is associated with an increased risk of ACM in the setting of low-risk but not intermediate- or high-risk PCa. This effect is driven by the subgroup of men with at least a single risk factor for CAD. These results warrant prospective validation given the widespread use of NHT for prostate downsizing prior to brachytherapy.
European urology 09/2012; · 7.67 Impact Factor
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ABSTRACT: Study Type - Therapy (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate-specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high-risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined-modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation-based regimens have been attempted but failed to accrue.
• To assess the risk of prostate cancer-specific mortality after therapy with radical prostatectomy (RP) or combined-modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen-suppression therapy (AST) in men with Gleason score 8-10 prostate cancer.
• Men with localised high-risk prostate cancer based on a Gleason score of 8-10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT. • Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer-specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors.
• As of January 2009, with a median (interquartile range) follow-up of 4.62 (2.4-8.2) years, there were 21 prostate cancer-specific deaths. • Treatment with RP was not associated with an increased risk of prostate cancer-specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-5.6, P= 0.3). • Factors associated with an increased risk of prostate cancer-specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3-16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1-7.2; P= 0.03) as compared with T1c, 2a.
• Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer-specific mortality in men with Gleason score 8-10 prostate cancer.
BJU International 04/2012; 110(8):1116-21. · 2.84 Impact Factor
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ABSTRACT: We investigated whether the decrease in death from cardiovascular disease, a major competing risk, explains the observed increase in prostate cancer specific mortality before 1992.
Between 1991 and 2006, 1,880 men with known cardiovascular disease underwent radiation therapy for prostate cancer and were followed until July 2008. Cox regression multivariable analysis was performed to assess whether known prostate cancer prognostic factors, history of coronary artery revascularization for cardiovascular disease, age, Charlson comorbidity score and prostate cancer treatment were associated with the risk of death.
Despite a significantly higher Charlson comorbidity score (p<0.001) due to a higher rate of prior myocardial infarction, the risk of death was significantly lower (adjusted hazard ratio 0.63, 95% CI 0.49-0.82, p<0.001) in men who underwent revascularization. High grade prostate cancer contributed significantly to the risk of death in men who underwent revascularization (AHR 1.74, 95% CI 1.04-2.91, p=0.04) but not in those who did not (AHR 1.18, 95% CI 0.88-1.58, p=0.27).
The availability of and appropriate selection for revascularization may explain the increase in prostate cancer specific mortality before 1992. Men with cardiovascular disease in whom revascularization was not appropriate could consider active surveillance of prostate cancer because the increased risk of death was not associated with high grade prostate cancer.
The Journal of urology 09/2011; 186(3):898-902. · 4.02 Impact Factor
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ABSTRACT: The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population.
The study cohort comprised 764 men aged > or = 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM.
The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017).
Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer.
Cancer 03/2010; 116(11):2590-5. · 4.77 Impact Factor
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ABSTRACT: To identify clinical factors associated with prostate cancer-specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy.
The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/mL or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk of PCSM.
After a median follow-up of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was significantly associated with a decreased risk of PCSM (adjusted hazard ratio, 0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (adjusted hazard ratio 1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (p = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL).
In elderly men with intermediate-risk prostate cancer, CVD status is a negative predictor of PCSM and affects the prognostic capacity of pretreatment PSA level. These observations support the potential utility of prerandomization stratification by comorbidity to more accurately assess prognostic factors and treatment effects within this population.
International journal of radiation oncology, biology, physics 10/2009; 77(1):147-52. · 4.59 Impact Factor
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ABSTRACT: We estimated the risk of prostate cancer (PC) -specific mortality (PCSM) after brachytherapy alone or in conjunction with androgen suppression therapy (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC.
The study cohort comprised 1,342 men with a prostate-specific antigen level more than 20 ng/mL and clinical T3 or 4 and/or Gleason score 8 to 10 disease. Competing risks multivariable regression was performed to estimate the risk of PCSM in men treated with brachytherapy alone or with supplemental AST, EBRT, or both, adjusting for age, year of treatment, and known PC prognostic factors.
Despite higher baseline probabilities of PCSM after a median follow-up of 5.1 years, there was a significant reduction in the risk of PCSM (adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006) in men treated with brachytherapy and both AST and EBRT as compared with neither. When compared with brachytherapy alone, a significant decrease in the risk of PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95% CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26). There was a near-significant reduction (AHR, 0.53; 95% CI, 0.27 to 1.07; P = .079) in the risk of PCSM in men treated with tri- as compared with bimodality therapy.
Supplemental AST and EBRT but not either supplement compared with brachytherapy alone was associated with a decreased risk of PCSM in men with high-risk PC.
Journal of Clinical Oncology 08/2009; 27(24):3923-8. · 18.37 Impact Factor
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ABSTRACT: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy.
The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >or=8, or clinical category >or=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors.
After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM.
In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.
International journal of radiation oncology, biology, physics 06/2009; 76(5):1439-44. · 4.59 Impact Factor
