ABSTRACT
BACKGROUND: The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). PATIENTS AND METHODS: A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. The median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration, 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason score ≥ 7; prostate-specific antigen ≥ 10 ng/mL; or stage ≥ T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. The interaction between radiation volume and ADT use was assessed. RESULTS: After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = .01), or with ADT use (AHR, 0.71; 95% CI, 0.58-0.90; P = .004). However, a combination of WPRT and ADT did not further improve ACM compared with either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the radiotherapeutic treatment volume and ADT (AHR, 1.61; 95% CI, 1.004-2.58; P = .048). CONCLUSION: Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, although a combination of the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes.
Subject(s)
Androgen Antagonists/therapeutic use , Prostatic Neoplasms/mortality , Prostatic Neoplasms/therapy , Radiotherapy/methods , Aged , Humans , Male , Neoplasm Grading , Pelvis/radiation effects , Prospective Studies , Prostate/radiation effects , Prostatic Neoplasms/pathology , Regression Analysis , Treatment OutcomeABSTRACT
Radiation therapy and immunotherapy in partnership may have the capability of delivering a therapeutic effect exceeding the sum of its parts. The possible relationship has been demonstrated in murine models and has been extended to a variety of clinical trials. Though the standard notion of whole body radiation therapy is immunosuppressive, there is growing evidence toward the contrary for focal radiation therapy. Furthermore, if immunotherapeutic techniques can retune the immune system against cancerous cells, they should have obvious benefits for advanced treatments moving forward. Herein, we explore the promise in combining radiation therapy and immunotherapy with distinct focus on potential morbidities and toxicities through analysis of completed clinical trials.
Subject(s)
Neoplasms/therapy , Clinical Trials as Topic , Combined Modality Therapy/adverse effects , Humans , Immunotherapy/adverse effects , Radiotherapy, Adjuvant/adverse effectsABSTRACT
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 Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use
, Brachytherapy
, Prostatic Neoplasms/drug therapy
, Aged
, Aged, 80 and over
, Coronary Artery Disease/epidemiology
, Coronary Artery Disease/etiology
, Humans
, Male
, Middle Aged
, Neoadjuvant Therapy
, Prostatic Neoplasms/complications
, Prostatic Neoplasms/radiotherapy
, Retrospective Studies
, Risk Assessment
, Risk Factors
ABSTRACT
PURPOSE: To determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer. METHODS AND MATERIALS: We analyzed 5972 men with T1c-T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed. RESULTS: ADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02-4.17; p=0.04]) or not (AHR, 1.8 [95% CI, 1.05-3.20; p = 0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p=0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR = 2.21 [1.04-4.68]; p=0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33-1.22]; p=0.17). CONCLUSIONS: ADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men.
Subject(s)
Androgen Antagonists/administration & dosage , Brachytherapy/methods , Myocardial Infarction/epidemiology , Prostatic Neoplasms/therapy , Aged , Cause of Death/trends , Comorbidity , Follow-Up Studies , Humans , Incidence , Male , Neoadjuvant Therapy , Prostatic Neoplasms/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate/trends , United States/epidemiologyABSTRACT
BACKGROUND: Sipuleucel-T is an autologous cellular immunotherapy approved by the US Food and Drug Administration for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Its mechanism of action is based on stimulation of the patient's own immune system to target prostate cancer. Peripheral blood mononuclear cells, including antigen-presenting cells and T cells, are obtained from patients via leukapheresis and treated ex vivo with PA2024, a fusion protein consisting of prostatic acid phosphatase/granulocyte-macrophage colony-stimulating factor antigen. METHODS: Data relating to the potential pharmacodynamic biomarkers associated with sipuleucel-T activity are reviewed, as well as considerations for patient selection and for sequencing sipuleucel-T with other prostate cancer treatments. Possible directions for future development are also discussed, including treatment of less advanced prostate cancer populations, combination treatment, and immune modulation. RESULTS: Data from three randomized, double-blind, placebo-controlled phase III clinical trials of sipuleucel-T in patients with metastatic castration-rresistant prostate cancer have shown improvement in overall survival vs control. Here, we review its developing role in prostate cancer therapy and future directions for development. CONCLUSIONS: There is potential to build on sipuleucel-T to further advance immunotherapy of prostate cancer.
Subject(s)
Cancer Vaccines/therapeutic use , Prostatic Neoplasms/therapy , Tissue Extracts/therapeutic use , Antigen-Presenting Cells/immunology , Combined Modality Therapy , Humans , Immunotherapy , Leukapheresis , Leukocytes, Mononuclear/immunology , Male , Orchiectomy , Prostatic Neoplasms/immunology , Prostatic Neoplasms/mortality , T-Lymphocytes/immunology , Tissue Extracts/adverse effectsABSTRACT
UNLABELLED: 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. OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Brachytherapy , Prostatectomy , Prostatic Neoplasms/therapy , Aged , Combined Modality Therapy , Humans , Male , Middle Aged , Prostatic Neoplasms/mortality , Survival RateABSTRACT
PURPOSE: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. METHODS AND MATERIALS: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. RESULTS: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). CONCLUSIONS: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.
Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/radiotherapy , Brachytherapy/mortality , Prostatic Neoplasms/mortality , Prostatic Neoplasms/therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Aged , Androgen Antagonists/therapeutic use , Brachytherapy/methods , Cause of Death , Combined Modality Therapy/methods , Combined Modality Therapy/mortality , Confidence Intervals , Follow-Up Studies , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. METHODS AND MATERIALS: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. RESULTS: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). CONCLUSIONS: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.
Subject(s)
Androgen Antagonists/adverse effects , Heart Failure/mortality , Myocardial Infarction/mortality , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/mortality , Aged , Androgen Antagonists/therapeutic use , Brachytherapy/methods , Cause of Death , Follow-Up Studies , Heart Failure/complications , Humans , Male , Myocardial Infarction/complications , Neoplasm Staging , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatic Neoplasms/complications , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapyABSTRACT
PURPOSE: It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. METHODS AND MATERIALS: Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings. RESULTS: Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10. CONCLUSION: Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease.
Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Biopsy , Confidence Intervals , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Digital Rectal Examination , Humans , Male , Middle Aged , Neoplasm Grading , Odds Ratio , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/complications , Prostatic Neoplasms/ethnology , Regression AnalysisABSTRACT
PURPOSE: Black men present more frequently with high grade prostate cancer and are more likely to have diabetes mellitus. We evaluated whether there is an independent association between diabetes mellitus and the risk of high grade prostate cancer in men diagnosed with prostate cancer and treated with radiation therapy. MATERIALS AND METHODS: A polychotomous logistic regression analysis was performed to evaluate whether a diagnosis of diabetes mellitus was associated with the odds of Gleason score 7 or 8-10 prostate cancer in a cohort of 16,286 men, adjusting for black race, advancing age, prostate specific antigen and digital rectal examination findings. RESULTS: Black men (adjusted OR 1.84, 95% CI 1.08-3.13, p = 0.024) and nonblack men (adjusted OR 1.59, 95% CI 1.33-1.89, p <0.001) with diabetes were more likely to have Gleason score 8-10 vs 6 or less prostate cancer than nondiabetic men. However, this was not true for Gleason score 7 vs 6 or less prostate cancer. Black race was significantly associated with Gleason score 7 vs 6 or less prostate cancer in men without and with diabetes (adjusted OR 1.38, 95% CI 1.17-1.63, p <0.001 and 1.61, 95% CI 1.17-2.21, p = 0.003, respectively). Black race was also associated with Gleason score 8-10 vs 6 or less prostate cancer in men without and with diabetes (adjusted OR 1.36, 95% CI 1.01-1.83, p = 0.04 and 1.58, 95% CI 0.98-2.53, p = 0.06, respectively). CONCLUSIONS: In a cohort of men undergoing radiotherapy for prostate cancer the diagnosis of diabetes mellitus was significantly associated with an increased risk of being diagnosed with Gleason score 8-10 prostate cancer independent of black race.
Subject(s)
Black or African American , Diabetes Complications/epidemiology , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/radiotherapy , Humans , Male , Neoplasm Grading , Prostatic Neoplasms/pathologyABSTRACT
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Subject(s)
Cardiovascular Diseases/complications , Cardiovascular Diseases/surgery , Myocardial Revascularization , Prostatic Neoplasms/complications , Prostatic Neoplasms/mortality , Cause of Death , Humans , Male , Prognosis , Prostatic Neoplasms/radiotherapy , Risk FactorsABSTRACT
PURPOSE: Radical prostatectomy and brachytherapy are widely used treatments for favorable risk prostate cancer. We estimated the risk of prostate cancer specific mortality following radical prostatectomy or brachytherapy in men with low or intermediate risk prostate cancer using prospectively collected data. MATERIALS AND METHODS: The study cohort comprised 5,760 men with low risk prostate cancer (prostate specific antigen 10 ng/ml or less, clinical category T1c or 2a and Gleason score 6 or less), and 3,079 with intermediate risk prostate cancer (prostate specific antigen 10 to 20 ng/ml, clinical category T2b or T2c, or Gleason score 7). Competing risks multivariable regression was performed to assess the risk of prostate cancer specific mortality after radical prostatectomy or brachytherapy, adjusting for age, year of treatment, cardiovascular comorbidity and known prostate cancer prognostic factors. RESULTS: After a median followup of 4.2 years (IQR 2.0-7.4) for low risk and 4.8 years (IQR 2.2-8.1) for intermediate risk men, there was no significant difference in the risk of prostate cancer specific mortality among low risk (adjusted hazard ratio 1.62, 95% CI 0.59-4.45, p = 0.35) or intermediate risk men (AHR 2.30, 95% CI 0.95-5.58, p = 0.07) treated with brachytherapy compared with radical prostatectomy. The only factor associated with an increased risk of prostate cancer specific mortality (AHR 1.05, 95% CI 1.01-1.10, p = 0.03) was increasing age at treatment in intermediate risk men. CONCLUSIONS: The risk of prostate cancer specific mortality in men with low or intermediate risk prostate cancer was not significantly different following radical prostatectomy vs brachytherapy.
Subject(s)
Brachytherapy , Prostatectomy , Prostatic Neoplasms/mortality , Prostatic Neoplasms/therapy , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Prospective Studies , Prostatectomy/methods , Risk FactorsABSTRACT
PURPOSE: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. METHODS: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. RESULTS: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). CONCLUSIONS: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.
Subject(s)
Adenocarcinoma , Black People , Brachytherapy/mortality , Hispanic or Latino , Prostatic Neoplasms , White People , Adenocarcinoma/ethnology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Aged , Androgen Antagonists/therapeutic use , Cause of Death , Cohort Studies , Humans , Male , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Neoplasm Grading , Neoplasm Staging , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Regression Analysis , Risk Factors , Socioeconomic Factors , Treatment OutcomeABSTRACT
BACKGROUND: Brachytherapy for prostate cancer can be technically challenging in men with small prostates (≤20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. METHODS AND MATERIALS: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume ≤20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. RESULTS: 443 patients (6.9%) had a prostate volume ≤20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume ≤20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for ≤20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). CONCLUSION: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume ≤20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.
Subject(s)
Brachytherapy , Prostate/pathology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Aged , Androgen Antagonists/therapeutic use , Brachytherapy/methods , Cause of Death , Contraindications , Follow-Up Studies , Humans , Male , Organ Size , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Regression AnalysisABSTRACT
BACKGROUND: A study was undertaken to determine the impact of prior coronary revascularization (angioplasty, stent, or coronary artery bypass graft) on the risk of all-cause mortality after neoadjuvant hormonal therapy (HT) for prostate cancer (PC) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). METHODS: Among 7839 men who received radiation with or without a median of 4 months of HT for PC from 1991 to 2006, 495 (6.3%) had CAD-induced CHF or MI and formed the study cohort. Of these men, 250 (50.5%) had been revascularized before treatment for PC. Cox regression was used to determine whether HT increased the risk of all-cause mortality, and whether revascularization altered this risk, after adjusting for known PC prognostic factors and a propensity score for revascularization. RESULTS: Median follow-up was 4.1 years. Neoadjuvant HT was associated with an increased risk of all-cause mortality (28.9% vs 15.7% at 5 years; adjusted hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.13-2.64; P = .01). Men who received HT without revascularization had the highest risk of all-cause mortality (33.3%; adjusted HR, 1.48; 95% CI, 1.01-2.18; P = .047), whereas men who were revascularized and did not receive HT had the lowest risk of all-cause mortality (9.4%; adjusted HR, 0.51; 95% CI, 0.28-0.93; P = .028). The reference group had an intermediate risk of all-cause mortality (23.4%) and was comprised of men in whom HT use and revascularization were either both given or both withheld. CONCLUSIONS: In men with a history of CAD-induced CHF or MI, neoadjuvant HT is associated with an excess risk of mortality, which appears to be reduced but not eliminated by prior revascularization.
Subject(s)
Androgen Antagonists/adverse effects , Coronary Artery Bypass/adverse effects , Heart Failure/complications , Myocardial Infarction/etiology , Myocardial Infarction/surgery , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy , Angioplasty/adverse effects , Brachytherapy , Cause of Death , Combined Modality Therapy , Humans , Male , Neoadjuvant Therapy , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Risk , StentsABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Brachytherapy , Prostatic Neoplasms/mortality , Aged , Cardiovascular Diseases/complications , Cause of Death , Combined Modality Therapy , Humans , Male , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-ModulatedABSTRACT
OBJECTIVE: To examine the effect of short-course androgen-suppression therapy (AST) before brachytherapy on all-cause mortality (ACM) rates, stratified by the presence or absence of a history of myocardial infarction (MI) or stroke. AST is used to reduce prostate size to enable men with favourable-risk prostate cancer to undergo brachytherapy, but no disease-specific benefit has been reported for this practice, and AST use has been associated with an increased risk of ACM in some men with pre-existing cardiovascular disease. PATIENTS AND METHODS: The study comprised 12792 men with favourable-risk disease, i.e. a prostate-specific antigen (PSA) level of <20 ng/mL, Gleason score ≤7 and clinical category ≤T2c, treated between 1991 and 2007 at community-based medical centres with brachytherapy ± neoadjuvant AST. Multivariable Cox regression analysis was used to assess whether there were significant associations between AST use in men with a history of MI or stroke and the risk of ACM, adjusting for age, treatment year, and known prognostic factors of prostate cancer. RESULTS: After a median (interquartile range) follow-up of 3.8 (2.0-5.9) years there were 1557 deaths. The risk of ACM was lower in men with no history of MI or stroke than in those with this history, whether AST was used (adjusted hazard ratio 0.79, 95% confidence interval 0.67-0.92; P= 0.003) or not (0.74, 0.65-0.85; P < 0.001). However, men with a history of MI or stroke treated with AST had a greater risk of ACM than those not treated with AST (1.2, 1.05-1.38; P= 0.008). CONCLUSION: The use of short-course AST in men with a history of MI or stroke is associated with a greater risk of ACM in men with favourable-risk prostate cancer.
Subject(s)
Androgen Antagonists/adverse effects , Myocardial Infarction/chemically induced , Prostatic Neoplasms/therapy , Stroke/chemically induced , Aged , Aged, 80 and over , Androgens/metabolism , Brachytherapy , Cause of Death , Combined Modality Therapy , Epidemiologic Methods , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Prostatic Neoplasms/complications , Prostatic Neoplasms/mortality , Stroke/mortality , Treatment OutcomeABSTRACT
PURPOSE: In 1999, the American Brachytherapy Society (ABS) recommended brachy-monotherapy for men with low-risk prostate cancer because of the potential for increased toxicity with combined external beam radiotherapy (EBRT) and brachytherapy without the proof of increased efficacy. We investigated the patterns of care in the community in this patient population before and after the reporting of the ABS guideline. METHODS AND MATERIALS: The study cohort consisted of 4943 men (median age, 69.0 years) with low-risk prostate cancer treated with brachytherapy with or without supplemental EBRT from 1991 to 2007 across 21 community radiation oncology centers. Multivariable logistic regression analysis was performed to determine if there was a significant association between the year of brachytherapy, prostate-specific antigen level, clinical tumor (T) category, patient's age, and the use of supplemental EBRT. RESULTS: Supplemental EBRT was used in 647 men (13%). The EBRT use initially increased until 2001 and then decreased yielding a significant association (adjusted odds ratio [AOR], 0.92; p<0.001) between the EBRT use and the year of brachytherapy using a quadratic formulation. Specifically, EBRT use peaked at 24.6% in 2001 and subsequently declined to 3.3% by 2007. Men with clinical category T2a as compared with T1c disease (AOR, 1.43; p<0.001) were more likely to receive combined modality therapy. CONCLUSIONS: The use of supplemental EBRT in men with low-risk prostate cancer treated with brachytherapy has decreased since 2001. This change in practice patterns suggests gradual adoption of the 1999 ABS practice guidelines.
Subject(s)
Brachytherapy/statistics & numerical data , Brachytherapy/standards , Guideline Adherence/statistics & numerical data , Practice Guidelines as Topic , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/radiotherapy , Radiotherapy, Conformal/statistics & numerical data , Radiotherapy, Conformal/standards , Cohort Studies , Humans , Male , Middle Aged , Multivariate Analysis , Prevalence , Risk Assessment , Risk Factors , Treatment Outcome , United States/epidemiologyABSTRACT
BACKGROUND: Discrepancies exist regarding the impact of neoadjuvant hormone therapy (NHT) on the risk of all-cause mortality (ACM) in men who receive brachytherapy for localized prostate cancer. Therefore, the objective of the current study was to examine the effect of NHT on the risk of ACM in men with prostate cancer who receive with brachytherapy. METHODS: The study cohort included 2474 men with localized prostate cancer who either received NHT (N = 1083) or did not receive NHT (N = 1391) and brachytherapy without supplemental external beam radiation between 1991 and 2005 at centers within the 21st Century Oncology Consortium. All men had at least 2 years of follow-up. Low-risk, intermediate-risk, and high-risk disease was present in 65%, 23%, and 12% of men, respectively. A Cox regression multivariate analysis was used to evaluate the risk of ACM in men who received NHT compared with all others adjusting for age, prostate-specific antigen level, Gleason score, and tumor classification. RESULTS: After a median follow-up of 4.8 years (interquartile range, 3.3-7.5 years) and adjusting for known prostate cancer prognostic factors and age, treatment with NHT was associated significantly with an increased risk of ACM (adjusted hazard ratio, 1.24; 95% confidence interval, 1.01-1.53; P = .04) in men aged > or =73 years. In men who were younger than the median age of 73 years, hormone therapy use was not significant (P = .34). CONCLUSIONS: Compared with men who were younger than the median age of 73 years, men aged > or =73 years with localized prostate cancer who received brachytherapy and NHT had an increased risk of ACM compared with men who did not receive NHT.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Prostatic Neoplasms/mortality , Prostatic Neoplasms/radiotherapy , Age Factors , Aged , Brachytherapy , Cause of Death , Combined Modality Therapy , Humans , Male , Neoadjuvant Therapy , Prostatic Neoplasms/drug therapy , Retrospective StudiesABSTRACT
PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.