Causes of death in men undergoing androgen suppression therapy for newly diagnosed localized or recurrent prostate cancer

BACKGROUND.

The authors estimated and characterized mortality after androgen suppression therapy (AST) use in men with newly diagnosed localized and recurrent prostate cancer.

METHODS.

The study cohorts comprised 102 men who were randomized to radiation therapy (RT) and AST and 46 men who underwent salvage AST for recurrence from a randomized trial that compared external beam RT and 6 months of AST to RT. Cox regression multivariable analyses were performed to estimate the mortality hazard ratio (HR) in men with moderate to severe as compared with no or minimal comorbidity, adjusting for age and known prostate cancer prognostic factors.

RESULTS.

After a median follow‐up of 8.4 years (interquartile range: 7.2‐9.6 years), prostate cancer‐specific mortality (PCSM) comprised 13% and 75% of all mortality in men with newly diagnosed localized and recurrent prostate cancer, respectively. There was an increased risk of death in men with moderate to severe as compared with no or minimal comorbidity (adjusted HR [AHR], 11.5; 95% confidence interval [CI], 5.2‐25.6; P < .001) in men with newly diagnosed localized prostate cancer but not in men with recurrent prostate cancer (AHR, 2.5; 95% CI, 0.2‐37.8; P = .51).

CONCLUSIONS.

The ability to measure an increase in the risk of death in men with moderate to severe as compared with no or minimal comorbidity undergoing AST decreases as the risk of PCSM increases, which may explain the discordance in the literature regarding the risk of cardiovascular death and AST use. Cancer 2008. © 2008 American Cancer Society.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

Salvage radiation in men after prostate-specific antigen failure and the risk of death

BACKGROUND:

A survival benefit has been observed with salvage radiation therapy (RT) for prostate‐specific antigen (PSA) failure after radical prostatectomy (RP) in men with rapid rises in PSA doubling time (DT, <6 months). Whether such a benefit exits in men with a protracted PSA rise in DT (≥6 months) is unclear and was examined in the current study.

METHODS:

Of 4036 men who underwent RP at Duke University between 1988 and 2008, 519 experienced a PSA failure, had complete data, and were the subjects of this study. Univariate and multivariate Cox regression analyses were performed to evaluate whether salvage RT in men with either a rapid (<6 months) or a protracted (≥6 months) PSA DT was associated with the risk of all‐cause mortality adjusting for age at the time of PSA failure, known prostate cancer prognostic factors, and cardiac comorbidity.

RESULTS:

After a median follow‐up of 11.3 years after PSA failure, 195 men died. Salvage RT was associated with a significant reduction in all‐cause mortality for men with either a PSA DT of <6 months (adjusted hazard ratio [AHR], 0.53; P = .02) or a PSA DT of ≥6 months (AHR, 0.52; P = .003). In a subset of patients with comorbidity data at the time of PSA failure, salvage RT remained associated with a significant reduction in all‐cause mortality for both men with a PSA DT of <6 months (AHR, 0.35; P = .042) or a PSA DT of ≥6 months (AHR, 0.60; P = .04).

CONCLUSIONS:

Salvage RT for PSA DTs less than or in excess of 6 months is associated with a decreased risk in all‐cause mortality. Cancer 2011. © 2011 American Cancer Society.     

Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer : implications for management

BACKGROUND.

Among screened populations, it is unknown whether men with prostate cancer (PC) diagnosed at the initial screening (prevalent cases) have a different outcome than men who are diagnosed at subsequent screenings (incident cases) after adjusting for known prognostic factors.

METHODS.

The current study cohort was comprised of 1923 men from a prospective PC screening study who underwent radical prostatectomy (RP) between September 19, 1989 and May 22, 2002. Cox regression multivariate analysis was used to determine whether having prevalent PC versus incident PC was associated with the time to prostate‐specific antigen (PSA) failure after RP after adjusting for PSA level, Gleason score, clinical tumor (T) classification, and year of RP.

RESULTS.

Men with prevalent PC had higher PSA levels (P < .001) and more advanced clinical T classification (P < .001) than men with incident PC. After a median follow‐up of 6.1 years, factors that were associated with a significantly shorter time to PSA failure after RP were prevalent PC (adjusted hazard ratio [AHR], 1.8; 95% confidence interval [95% CI], 1.3‐2.6; P = .0005), baseline PSA (AHR, 1.07; 95%CI, 1.04‐1.09; P < .001), Gleason 7 disease (AHR, 2.5; 95% CI, 1.9‐3.3; P < .001), Gleason 8 to 10 disease (AHR, 2.3; 95%CI, 1.5‐3.5; P < .001), and the year of RP (AHR, 0.92; 95%CI, 0.86‐0.97; P = .003). Men with prevalent PC also had worse outcomes after adjusting for their more advanced pathologic features.

CONCLUSIONS.

After adjusting for known prognostic factors, men with prevalent PC had a poorer outcome after RP than men with incident PC. The authors believe that this finding should be taken into consideration when weighing the risk of recurrence and treatment options for men who are diagnosed with PC on their initial screening. Cancer 2008. © 2008 American Cancer Society.     

Comorbidity,body mass index,and age and the risk of nonprostate‐cancer‐specific mortality after a postradiation prostate‐specific antigen recurrence

BACKGROUND:

Some men with a postradiation therapy (RT) prostate‐specific antigen (PSA) recurrence will die of noncancer causes before developing metastases. Therefore, our ability to determine who would benefit from salvage hormonotherapy (HT) would be enhanced if an individual's risk of nonprostate‐cancer‐specific mortality were known.

METHODS:

Among 206 men with unfavorable‐risk localized prostate cancer initially randomized to RT+/?HT, 87 men who experienced PSA recurrence were studied. Fine and Gray's competing risks regression was used to assess whether body mass index (BMI) and the Adult Comorbidity Evaluation‐27 comorbidity level at randomization were associated with the risk of nonprostate‐cancer‐specific mortality after PSA recurrence, adjusting for age at recurrence.

RESULTS:

After a median postrecurrence follow‐up of 4.4 years, moderate/severe comorbidity (adjusted hazard ratio [HR] = 3.15; P = .02), BMI ≥ median (27.4 kg/m²; adjusted HR=2.98; p=.04), and increasing age at recurrence (adjusted HR = 1.17; P = .03) were significantly associated with an increased risk of nonprostate‐cancer‐specific mortality. Five‐year cumulative incidence estimates of nonprostate‐cancer‐specific mortality were as follows: 0% (95% confidence interval [CI] [0,0]) for low‐risk patients (mild/no comorbidity and age<median [76.2 years] and BMI<median), 18.8% (5.8‐31.8) for intermediate‐risk patients (mild/no comorbidity and either age≥median or BMI≥median); and 37.9% (95% CI, 6.8‐68.9) for high‐risk patients (moderate/severe comorbidity; P = .03 overall).

CONCLUSIONS:

After a post‐RT PSA recurrence, men with moderate/severe comorbidity and those who are obese or older face a substantial risk of nonprostate‐cancer‐specific mortality, and they could be considered for surveillance protocols with a plan to initiate salvage HT if the PSA rises rapidly (eg, PSA doubling time <6 months) or the patient develops clinically or radiographically evident disease. Cancer 2010. © 2009 American Cancer Society.     

Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50

BACKGROUND:

We previously reported that a single prostate‐specific antigen (PSA) measured at ages 44‐50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow‐up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage ≥T3 or metastases at diagnosis).

METHODS:

Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974‐1986 at ages 33‐50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls.

RESULTS:

At a median follow‐up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% CI, 0.70‐0.74; for advanced cancer, 0.75; 95% CI, 0.72‐0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% CI, 77%‐86%) found in men with PSA above the median (0.63 ng/mL at ages 44‐50).

CONCLUSIONS:

A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low‐risk men to be screened less often but increase frequency of testing on a more limited number of high‐risk men. This is likely to improve the ratio of benefit to harm for screening. Cancer 2011. © 2010 American Cancer Society.     

Major 30‐day complications after radical radiotherapy

BACKGROUND:

Radiotherapy (RT) is used commonly to treat localized prostate cancer, particularly among older men and men with comorbid illnesses. Few population‐based studies have reported on the rates of major short‐term complications that lead to hospitalization after radiotherapy.

METHODS:

In this study, the authors identified all men with nonmetastatic prostate cancer who received RT between 1990 and 1999 in Ontario, Canada. Patients who underwent a prior prostate‐directed surgery were excluded. Mortality and complications after RT were examined by using administrative data. A comprehensive list of 7 categories of complications was developed by combining published lists from radical prostatectomy series with input from experts. Logistic regression was used to analyze the relations between complications (that occurred within 30 days of RT) and clinical factors. A similar analysis was performed among men who underwent radical prostatectomy during the same period.

RESULTS:

There were 7661 men (mean age, 69 years) identified who received RT. Nine patients (0.1%) died within 30 days of RT. Any complication within 30 days of RT was experienced by 6.5% of patients. In analyses that were adjusted for year of treatment, increasing age was associated with any, respiratory, bleeding, genitourinary, and miscellaneous medical complications (P<.02) but not with cardiac, vascular, or bowel complications. Over time, any, cardiac, vascular, and genitourinary complications decreased, but the other 4 categories of complications did not decrease. Despite being older and having more comorbidity, men who received RT had lower complication rates in each category compared with 11,010 men who underwent radical prostatectomy.

CONCLUSIONS:

Short‐term complications that required hospital‐based management were relatively uncommon after RT, commonly increased with patient age, and generally declined over time. Cancer 2009. © 2009 American Cancer Society.     

Overtreatment of men with low-risk prostate cancer and significant comorbidity

BACKGROUND:

Men with low‐risk prostate cancer and significant comorbidity are susceptible to overtreatment. The authors sought to compare the impact of comorbidity and age on treatment choice in men with low‐risk disease.

METHODS:

The authors sampled 509 men with low‐risk prostate cancer diagnosed at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers between 1997 and 2004. Rates of aggressive treatment (radical prostatectomy, radiation therapy, brachytherapy) were determined among men of different ages and with different Charlson comorbidity scores. Multivariate modeling was used to determine the influence of both variables in predicting nonaggressive treatment, and Cox proportional hazards analysis was used to compare the risk of other‐cause mortality among groups according to Charlson score and age.

RESULTS:

Men with Charlson scores ≥3 were treated aggressively in 54% of cases (30 of 56 men), while men aged >75 years at diagnosis were treated aggressively in 16% of cases (7 of 44 men). In multivariate analysis, age >75 years was a much stronger predictor of nonaggressive treatment (relative risk, 12.0; 95% confidence interval [CI], 5.4‐28.3) than a Charlson score ≥3 (relative risk, 2.0; 95% CI, 1.3‐2.9). In survival analysis, men with Charlson scores ≥3 had an 8‐fold increased risk (hazard ratio, 8.4; 95% CI, 4.2‐16.6) and 70% probability of other‐cause mortality at 10 years, whereas age >75 years was associated with a 5‐fold increased risk (hazard ratio, 4.9; 95%CI, 1.7‐13.8) and a 24% probability of other‐cause mortality.

CONCLUSIONS:

Men with significant comorbidity often were overtreated for low‐risk prostate cancer. Like advanced age, significant comorbidity should be a strong relative contraindication to aggressive treatment in men with low‐risk disease. Cancer 2011. © 2010 American Cancer Society.     

Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture

BACKGROUND:

Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown.

METHODS:

From the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992‐2004 were identified. By using Kaplan‐Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall‐related fracture outside the radiation field.

RESULTS:

After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38‐2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56‐1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88‐3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17‐1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97‐2.10). The number needed to treat to result in 1 hip fracture during a 10‐year period was 51 patients (95% CI, 31‐103).

CONCLUSIONS:

In men with prostate cancer, pelvic 3‐D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short‐course AST to EBRT. This risk associated with EBRT must be site‐specific as there was no increase in the risk of fall‐related fractures in bones that were outside the radiation field. Cancer 2011. © 2011 American Cancer Society.     

Death from high‐risk prostate cancer versus cardiovascular mortality with hormonal therapy

BACKGROUND:

Randomized trials have demonstrated improved survival when hormonal therapy (HT) is added to radiation therapy (RT) for high‐risk prostate cancer. However, it is still unknown whether men who have a history of myocardial infarction (MI) or MI risk factors achieve a superior outcome from HT.

METHODS:

A Markov decision analysis model was used to compare quality‐adjusted life expectancy (QALE) in men aged 50, 60, and 70 years who received RT and no HT, 6 months of HT (short‐term), or 3 years of HT (long‐term) for high‐risk prostate cancer stratified by cardiac risk group.

RESULTS:

In men with a history of MI, there was a decrease of 0.1 to 0.2 quality‐adjusted life years and 0.5 to 0.6 quality‐adjusted life years across all ages with short‐term HT and long‐term HT, respectively, compared with no HT. In men without MI, receipt of short‐term or long‐term HT was associated with a QALE benefit versus no HT in all cohorts. Among men without MI, the optimal duration of HT was a function of age and the number of MI risk factors. Long‐term HT improved QALE (range, 1.4‐5.4 years) for men aged 50 or 60 years except those with MI; whereas, for men aged 70 years with 4 cardiac risk factors, short‐term and long‐term HT yielded identical QALE.

CONCLUSIONS:

Men who received RT for high‐risk prostate cancer and had a history of MI experienced net harm when they received HT. Men without MI gained a QALE benefit from HT, even if they had up to 4 cardiac risk factors. The optimal duration of HT is a function of patient age and the number of cardiac risk factors. Cancer 2013. © 2013 American Cancer Society.     

Treatment and survival outcomes in young men diagnosed with prostate cancer

BACKGROUND:

Outcomes of treatment for young men compared with older men with prostate cancer are poorly defined outside of limited institutional series. In this study, the authors examined the association between age at diagnosis and grade, stage, treatment, and survival outcomes in men who were diagnosed during the era of prostate‐specific antigen testing.

METHODS:

The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify men who were diagnosed with prostate cancer between 1988 and 2003. Men ages 35 years to 74 years were stratified by age at diagnosis to examine differences in tumor characteristics, treatment, and survival within each age group.

RESULTS:

In total, 318,774 men ages 35 years to 74 years were identified who had been diagnosed with adenocarcinoma of the prostate between 1988 and 2003. The proportion of men aged ≤55 years at diagnosis increased over the study period from 2.3% between the years 1988 and 1991 to 9% between the years 2000 and 2003, and the median age at diagnosis decreased from 72 years in 1988 to 68 years in 2003. Younger men were diagnosed less frequently with organ‐confined tumors (P < .001) but were less likely to be diagnosed with high‐grade cancer (P < .001). Older men were more likely to receive no local therapy or external beam radiation than young men (P < .001 for trend). Among men who had tumors with a Gleason score between 5 and 7, overall survival was worse with advancing age. However, among all age groups with high grade and stage, the youngest men (ages 35‐44 years) were at the highest risk of all‐cause and cancer‐specific death.

CONCLUSIONS:

Age at diagnosis among men with prostate cancer continued to decline. Younger men were more likely to undergo prostatectomy, have lower grade cancer, and, as a group, to have better overall and equivalent cancer‐specific survival at 10 years compared with older men. Among men with high grade and locally advanced prostate cancer, the youngest men had a particularly poor prognosis compared with older men. Cancer 2009. Published 2009 by the American Cancer Society.     

Age‐specific physical activity and prostate cancer risk among white men and black men

BACKGROUND:

The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men.

METHODS:

In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health‐AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk.

RESULTS:

During 7 years of follow‐up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in ≥4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43‐0.99 [P_trend = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% CI, 0.36‐0.96 [P_trend = .15]).

CONCLUSIONS:

Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009. Published 2009 by the American Cancer Society.     

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 ≥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. Cancer 2010. © 2010 American Cancer Society.     

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

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 ≥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 ≥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. Cancer 2010. © 2010 American Cancer Society.     

Do radiation use disparities influence survival in patients with advanced breast cancer?

BACKGROUND:

The authors previously identified racial/ethnic disparities in the use of radiation therapy (RT) in patients with advanced breast cancer (BC). They hypothesized that disparities in the use of RT were associated with survival differences favoring white patients.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results database to identify white, black, Hispanic, and Asian patients with BC associated with ≥10 metastatic lymph nodes diagnosed between 1988 and 2005. Multivariate analyses of overall survival (OS) and disease‐specific survival (DSS) assessed age, sex, race, tumor size, histology, estrogen receptor status, progesterone receptor status, RT, and type of surgery. The authors further stratified for use of RT and type of surgery. Risk of mortality was reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS:

Of 15,895 patients with advanced BC, 12,653 met entry criteria. On multivariate analysis, RT was associated with a decreased risk of all‐cause (HR, 0.78; 95% CI 0.74‐0.83; P < .001) and disease‐specific (HR, 0.81; 95% CI, 0.76‐0.86; P < .001) mortality; black race was associated with an increased risk of all‐cause (HR, 1.54; 95% CI, 1.42‐1.68; P < .001) and disease‐specific (HR, 1.53; 95% CI, 1.39‐1.68; P < .001) mortality. After stratifying by type of surgery and use of RT, blacks demonstrated poorer survival than their white counterparts, regardless of surgery type or receipt of RT.

CONCLUSIONS:

Only black patients had poorer OS and DSS relative to whites. When stratified by type of surgery and use of RT, blacks continued to demonstrate poorer survival. This survival disparity is unlikely to be because of lack of RT. Cancer 2012;. © 2011 American Cancer Society.     

Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer

BACKGROUND:

The natural history of castration‐resistant nonmetastatic prostate cancer is poorly defined.

METHODS:

The authors used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases in men with prostate cancer, rising prostate‐specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases. Relations between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N‐telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin.

RESULTS:

At 2 years, 46% of subjects had developed bone metastases, and 20% had died. Median bone metastasis‐free survival was 25 months. In multivariate analyses, baseline PSA ≥13.1 ng/mL was associated with shorter overall survival (relative risk [RR], 2.34; 95% confidence interval [CI], 1.71–3.21; P < .0001), time to first bone metastasis (RR, 1.98; 95% CI, 1.43‐2.74; P < .0001), and bone metastasis‐free survival (RR, 1.98; 95% CI, 1.45–2.70; P < .0001). PSA velocity was significantly associated with overall and bone metastasis‐free survival. Other covariates were not consistently associated with clinical outcomes.

CONCLUSIONS:

In men with progressive castration‐resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis‐free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes. Cancer 2011. © 2010 American Cancer Society.     

Dose‐escalated radiation therapy for intermediate‐risk prostate cancer

BACKGROUND:

Randomized trials supported the use of androgen deprivation therapy (ADT) with radiation therapy (RT) for intermediate‐risk prostate cancer. However, the value of concurrent ADT was less certain with dose‐escalated RT. Better methods of stratifying patients in this risk group may help select patients who are most likely to benefit.

METHODS:

A total of 238 men with intermediate‐risk (prostate specific antigen [PSA] 10‐20, Gleason 7, or stage T2b‐c) adenocarcinoma of the prostate were treated with external beam RT between 1989 and 2006. Patients had Gleason≤6 (39%) or 7 (61%) tumors; median PSA was 10.5 ng/mL. A median of 37.5% of biopsy cores were positive from a median of 9 biopsy cores sampled. The median RT dose was 74 Gy to the prostate. A total of 112 patients (47%) received neoadjuvant and concurrent ADT (median, 4 months). Median follow‐up period was 49 months.

RESULTS:

The freedom from biochemical failure (FFBF, nadir + 2 definition) was 93% at 3 years, 86% at 4 years, and 80% at 5 years. On univariate analysis, the only factor associated with FFBF was percentage of positive cores (PPC, P = .0340). The prognostic value of PPC≥50 was not evident in patients receiving ADT (FFBF at 4 years 90% vs 91%, P = .3015). For patients not receiving ADT, the impact of PPC≥50 (FFBF at 4 years 76% vs 93%, P = .0844) was more pronounced. On multivariate analysis, PPC (P = .0388) was significantly associated with FFBF, whereas Gleason sum, ADT, RT dose, PSA, and T‐stage were not.

CONCLUSIONS:

After dose‐escalated external beam RT, intermediate‐risk prostate cancer patients with PPC≥50 had the highest risk for biochemical failure and may be most likely to derive a benefit from ADT. Cancer 2009. © 2009 American Cancer Society.     

The use of anticoagulants improves biochemical control of localized prostate cancer treated with radiotherapy

BACKGROUND:

Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.

METHODS:

The study cohort consisted of 662 patients with adenocarcinoma of the prostate who received radiotherapy (RT) with curative intent. Among those 622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin). All patients received external‐beam RT, permanent seed implantation, or a combination of both. Prostate‐specific antigen (PSA) values were monitored for biochemical control of disease.

RESULTS:

At a median follow‐up of 49 months, the biochemical control rate at 4‐years was significantly better in patients who received ACs at 91% compared with 78% in patients who did not receive ACs (P = .0002). The distant metastasis rate at 4 years also was reduced in the AC group compared with the non‐AC group (1% vs 5%; P = .0248). In subgroup analysis, the improvement in biochemical control was significant only for patients with high‐risk disease. Along with Gleason score, T classification, and initial PSA, the use of AC therapy was associated independently with improved biochemical control in multivariate analysis.

CONCLUSIONS:

AC therapy was associated with an improvement in biochemical control in patients with prostate cancer who received RT with curative intent. The effect was most prominent in patients who had high‐risk disease. Cancer 2010. © 2010 American Cancer Society.     

Rates and predictors of colorectal cancer screening by race among motivated men participating in a Prostate Cancer Risk Assessment Program

BACKGROUND:

Screening by fecal occult blood test and lower endoscopy has lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between white and African American men. The goal of this study was to assess for disparities in uptake of CRC screening among men participating in a high‐risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening.

METHODS:

Baseline data on a racially diverse cohort of men aged 50 to 69 years at increased risk of prostate cancer collected via the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariate logistic regression.

RESULTS:

Compared with whites, African American men had statistically significantly lower uptake of fecal occult blood testing (African American 49.0% vs white 60.7%, P = .035), lower endoscopy (African American 44.1% vs white 58.5%, P = .011), and any CRC screening (African American 66.2% vs white 76.3%, P = .053). Predictors of uptake of lower endoscopy among African American men included older age (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.87‐6.97), family history of CRC (OR, 3.47; 95% CI, 1.30‐9.25), and insurance status (OR, 1.90; 95% CI, 1.04‐3.46).

CONCLUSIONS:

Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger African American men with and without a family history of CRC are needed. Cancer 2011;. © 2011 American Cancer Society.