Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer-Specific Mortality Stratified by the Extent of Competing Mortality.

PURPOSE: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. METHODS AND MATERIALS: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. RESULTS: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). CONCLUSIONS: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

Whole Pelvis Versus Prostate-Only Radiotherapy With or Without Short-Course Androgen Deprivation Therapy and Mortality Risk.

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.

Neoadjuvant hormonal therapy use and the risk of death in men with prostate cancer treated with brachytherapy who have no or at least a single risk factor for coronary artery disease.

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

Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer.

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.

Type of diabetes mellitus and the odds of Gleason score 8 to 10 prostate cancer.

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.

Diabetes mellitus, race and the odds of high grade prostate cancer in men treated with radiation therapy.

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.

Cholinergic control of male mating behavior in hamsters: effects of central oxotremorine treatment.

The responses of rats to intracranial injections of cholinergic drugs implicate acetylcholine in the control of male mating behavior and suggest specific brain areas as mediators of these effects. In particular, past work has linked the medial preoptic area (MPOA) to the control of intromission frequency but implicated areas near the lateral ventricles in effects on the initiation and spacing of intromissions. Studies of responses to systemic cholinergic treatments suggest that acetylcholine is even more important for the control of mating behavior in male hamsters but provide no information on the relevant brain areas. To fill this gap, we observed the effects of central injections of the cholinergic agonist oxotremorine that approached the MPOA along contrasting paths. Both studies suggest that increased cholinergic activity in or near the MPOA can facilitate behavior by reducing the postejaculatory interval and possibly affecting other parts of the mechanisms controlling the initiation of copulation and the efficiency of performance early in an encounter. In addition, oxotremorine caused other changes in behavior that could not be tied to the MPOA and may reflect actions at more dorsal sites, possibly including the bed nucleus of the stria terminalis and medial septum. These effects were notably heterogeneous, including facilitatory and disruptive effects on male behavior along with a facilitation of lordosis responses to manual stimulation. These results emphasize the number and diversity of elements of sexual behavior in hamsters that are under the partial control of forebrain cholinergic mechanisms.

Coronary artery revascularization and the risk of death in men with prostate cancer.

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.

Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low or intermediate risk disease.

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.

Race and survival following brachytherapy-based treatment for men with localized or locally advanced adenocarcinoma of the prostate.

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.

Coronary revascularization and mortality in men with congestive heart failure or prior myocardial infarction who receive androgen deprivation.

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.

Risk of all-cause and prostate cancer-specific mortality after brachytherapy in men with small prostate size.

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.

Prostate cancer-specific mortality and the extent of therapy in healthy elderly men with high-risk prostate cancer.

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.

The use of supplemental external beam radiotherapy in men with low-risk prostate cancer undergoing brachytherapy before and after the 1999 American Brachytherapy Society Guideline statement.

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.

Androgen-suppression therapy for prostate cancer and the risk of death in men with a history of myocardial infarction or stroke.

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.

Mortality in men with localized prostate cancer treated with brachytherapy with or without neoadjuvant hormone therapy.

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.

Predictors of prostate cancer-specific mortality in elderly men with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.

Total androgen blockade versus a luteinizing hormone-releasing hormone agonist alone in men with high-risk prostate cancer treated with radiotherapy.

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.

Risk of death from prostate cancer after brachytherapy alone or with radiation, androgen suppression therapy, or both in men with high-risk disease.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Surgically (laparotomy/laparoscopy) guided placement of high dose rate interstitial irradiation catheters (LG-HDRT): technique and outcome.

OBJECTIVE: To describe and evaluate the technique and the clinical outcome of a new modality for the treatment of women with persistent or recurrent pelvic malignancies utilizing surgically (laparotomy or laparoscopic) guided high dose rate (HDR) catheters to complete high dose rate interstitial irradiation therapy (LG-HDRT). METHODS: Between 6/2000 and 6/2004, 14 women with histologic evidence of postradiation persistent (3 patients) or recurrent (11 patients) pelvic disease underwent LG-HDRT. Five patients (36%) received treatment for a 2nd, 3rd or 4th recurrence. Preoperative clinical and radiologic evaluation to exclude evidence of extrapelvic disease was routine. Initial intraoperative evaluation included intraabdominal inspection and or biopsy to determine the extent of disease. A two "team" approach was used to place the 100 cm Teflon after loading HDR catheters. Each catheter had its open ends closed with bone wax prior to placement. Using a 14 gauge intravenous catheter as a guide, each HDR catheter was individually placed transvaginally. The tumor bed (treatment volume) was marked circumferentially with clips to facilitate treatment planning. Dosimetry was typically completed on the day of surgery and HDR therapy was started within the initial 24 postoperative hours. The catheters were removed transvaginally, without anesthesia following completion of therapy. RESULTS: Mean patient age was 63.1 years and weight was 138.2 lb. Squamous cell cancer of the vagina or cervix was the most common (64%) diagnosis. The mean time from initial diagnosis to LG-HDRT was 67.9 months. The procedure was completed laparoscopically in 71% of patients, with 4 patients requiring laparotomy (3 conversions from laparoscopy). The mean duration of surgery was 94.9 min and the mean hospital stay was 4.8 days. Only 2 patients (14%) were discharged prior to the completion of therapy. The mean number of catheters placed was 6.1 and the mean dose delivered was 20 Gy over a mean of 5 fractions. There were no major intraoperative complications. Postradiation complications were limited to DVT (1), bladder bleeding (1),