Comorbidity and competing risks for mortality in men with prostate cancer

BACKGROUND:

Accurate estimation of life expectancy is essential for men deciding between aggressive and conservative treatment of prostate cancer. The authors sought to assess the competing risks of nonprostate cancer and prostate cancer mortality among men with differing Charlson comorbidity index scores and tumor risks.

METHODS:

The authors conducted a retrospective study of 1482 men with nonmetastatic prostate cancer diagnosed from 1997 to 2004 at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers. They performed Kaplan‐Meier and competing risks regression analyses to assess survival outcomes.

RESULTS:

After a mean follow‐up of 6.0 years, 370 (25%) men died from other causes, whereas 44 (3%) died of prostate cancer. At 10 years after diagnosis, men with Charlson scores 0, 1, 2, and 3+ had nonprostate cancer mortality rates of 17%, 34%, 52%, and 74%, respectively. In competing risks regression analysis, each point increase in Charlson score was associated with a 2‐fold increase in hazard of nonprostate mortality. Men with Charlson 3+ had 8.5× the hazard of death from other causes, compared with men with the lowest scores (subhazard ratio, 8.5; 95% confidence interval, 6.2‐11.7). After stratification by tumor risk, nonprostate mortality rates remained markedly elevated among men with higher Charlson scores, whereas prostate cancer mortality was rare, especially among low‐risk and intermediate‐risk groups (0.4%, 3%, and 8% for low, intermediate, and high risk, respectively).

CONCLUSIONS:

Men with the highest Charlson scores should consider conservative management of low‐risk and intermediate‐risk tumors, given their exceedingly high risk of death from other causes and low risk of prostate cancer mortality. Cancer 2011;. © 2011 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.     

Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel

Background

Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study.

Methods

Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis.

Results

Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87–1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79–1.17], p = 0.69).

Conclusions

Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel.     

Alcohol consumption,finasteride, and prostate cancer risk

BACKGROUND:

Current research is inconclusive regarding the relation between alcohol consumption and prostate cancer risk. In this study, the authors examined the associations of total alcohol, type of alcoholic beverage, and drinking pattern with the risk of total, low‐grade, and high‐grade prostate cancer.

METHODS:

Data for this study came from the 2129 participants in the Prostate Cancer Prevention Trial (PCPT) who had cancer detected during the 7‐year trial and 8791 men who were determined by biopsy to be free of cancer at the trial end. Poisson regression was used to calculate relative risks (RRs) and 95% confidence intervals (95% CIs) for associations of alcohol intake with prostate cancer risk.

RESULTS:

Associations of drinking with high‐grade disease did not differ by treatment arm. In combined arms, heavy alcohol consumption (≥50 g of alcohol daily) and regular heavy drinking (≥4 drinks daily on ≥5 days per week) were associated with increased risks of high‐grade prostate cancer (RR, 2.01 [95% CI, 1.33‐3.05] and 2.17 [95% CI, 1.42‐3.30], respectively); less heavy drinking was not associated with risk. Associations of drinking with low‐grade cancer differed by treatment arm. In the placebo arm, there was no association of drinking with risk of low‐grade cancer. In the finasteride arm, drinking ≥50 g of alcohol daily was associated with an increased risk of low‐grade disease (RR, 1.89; 95% CI, 1.39‐2.56); this finding was because of a 43% reduction in the risk of low‐grade cancer attributable to finasteride treatment in men who drank <50g of alcohol daily and the lack of an effect of finasteride in men who drank ≥50 g of alcohol daily (P_interaction = .03).

CONCLUSIONS:

Heavy, daily drinking increased the risk of high‐grade prostate cancer. Heavy drinking made finasteride ineffective for reducing prostate cancer risk. Cancer 2009. © 2009 American Cancer Society.     

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.     

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.     

Inappropriate utilization of radiographic imaging in men with newly diagnosed prostate cancer in the United States

BACKGROUND:

The use of radiographic imaging (bone scan and computerized tomography) is only recommended for men diagnosed with high‐risk prostate cancer characteristics. The authors sought to characterize utilization patterns of imaging in men with newly diagnosed prostate cancer.

METHODS:

The authors performed a population‐based observational cohort study using the US Surveillance, Epidemiology, and End Results‐Medicare linked data to identify 30,183 men diagnosed with prostate cancer during 2004 to 2005.

RESULTS:

Thirty‐four percent of men with low‐risk and 48% with intermediate‐risk prostate cancer underwent imaging, whereas only 60% of men with high‐risk disease received imaging before treatment. Radiographic imaging utilization was greater for men who were older than 75 years (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.20‐1.37; P < .001), were black (OR, 1.11; 95% CI, 1.01‐1.21; P = .030), resided in wealthier areas (OR, 1.19; 95% CI, 1.08‐1.32 for median income >$60,000 vs <$35,000; P < .001), lived in rural regions (OR, 1.23; 95% CI, 1.12‐1.36; P < .001), or underwent standard radiation therapies (OR, 1.71; 95% CI, 1.60‐1.84; P < .001). Imaging utilization was less for men living in areas with greater high school education (OR, 0.83; 95% CI, 0.75‐0.91 between highest and lowest graduation rates; P < .001) or opting for active surveillance (OR, 0.17; 95% CI, 0.15‐0.19 vs radical prostatectomy; P < .001). The estimated cost of unnecessary imaging over this 2‐year period exceeded $3.6 million.

CONCLUSIONS:

In the United States, there is widespread overutilization of imaging for low‐risk and intermediate‐risk prostate cancer, whereas a worrisome number of men with high‐risk disease did not receive appropriate imaging studies to exclude metastases before therapy. Cancer 2012;. © 2011 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.     

Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

A significant proportion of screen‐detected men with prostate cancer is likely to be overtreated, especially in older age groups. We aim to find which groups of screen‐detected older men (65+) benefit the most from Immediate Radical Treatment or Active Surveillance (AS) for prostate cancer, depending on age, screening history, health status and prostate cancer stage at detection. We used a microsimulation model (MISCAN) of the natural history of prostate cancer based on ERSPC data. Individual life histories are simulated with US comorbidity lifetables based on a random sample of MEDICARE data. Different screening histories are simulated and we count outcomes for men screen‐detected from ages 66 to 72. For immediately treated men with low‐risk disease (≤ T2a, Gleason 6) the probability of overtreatment ranges from 61% to 86% decreasing to between 37 and 46%, if they are assigned to AS. For intermediate risk men (≤T2, Gleason 3 + 4) overtreatment ranges from 23 to 60%, which reduces to between 16 and 31% for AS. For high risk men (T3, or ≥ Gleason 4 + 3), overtreatment ranges from 11 to 51%. The disease stage at screen‐detection is a critical risk factor for overtreatment. For low risk men, AS seems to significantly reduce overtreatment at a modest cost. For intermediate risk men, the decision between immediate treatment or AS depends on age and comorbidity status. Men screen‐detected in a high risk disease stage may benefit from immediate treatment even beyond age 69.     

Impact of comorbidity in elderly prostate cancer patients treated with brachytherapy

Objective

To analyze the correlations among comorbidity and overall survival (OS), biochemical progression-free survival (b-PFS) and toxicity in elderly patients with localized prostate cancer treated with ¹²⁵I brachytherapy.

Methods

Elderly men, aged ≥65 years, with low-intermediate risk prostate cancer, were treated with permanent ¹²⁵I brachytherapy as monotherapy. Comorbidity data were obtained from medical reports using age-adjusted Charlson comorbidity index (a-CCI). The patients were categorized into two age groups (<75 and ≥75 years old), and two comorbidity score groups (a-CCI ≤3 and >3). Toxicity was scored with Radiation Therapy Oncology Group (RTOG) scale.

Results

From June 2003 to October 2009, a total of 92 elderly patients underwent prostate brachytherapy, including 57 men (62%) with low-risk prostate cancer, and 35 men (38%) with intermediate-risk prostate cancer. The median age of patients was 75 years (range, 65-87 years). Forty-seven patients (51%) had a-CCI ≤3 and 45 patients (49%) a-CCI >3. With a median follow-up period of 56 months (range, 24-103 months), the 5-year actuarial OS and b-PFS were 91.3% and 92.4% respectively, without statistical significance between two Charlson score groups. Toxicity was mild. None of the patients experienced gastrointestinal (GI) toxicity, and only 4 patiens (4%) experienced late genitourinary (GU) grade-3 (G3) toxicity. No correlation between acute GU and GI toxicity and comorbidity was showed (P=0.50 and P=0.70, respectively).

Conclusions

Our data suggest that elderly men with low-intermediate risk prostate cancer and comorbidity can be considered for a radical treatment as ¹²⁵I low-dose rate brachytherapy.Key Words: Prostate cancer, brachytherapy, elderly, comorbidity, toxicity, overall survival, biochemical control     

Psychiatric treatment in men with prostate cancer--results from a Nation-wide, population-based cohort study from PCBaSe Sweden

Aim

To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment.

Methods

PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants.

Findings

In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14-1.45), RR 1.42 (95% CI 1.12-1.80) and RR 1.61 (95% CI 1.16-2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45-3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54-1.77) and treatment strategies RR 1.93 (95% CI 1.75-2.13).

Interpretation

Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders.     

Comorbidities and mammography use interact to explain racial/ethnic disparities in breast cancer stage at diagnosis

BACKGROUND:

Interactions with comorbidity burden and comorbidity‐related care have not been examined as potential explanations for racial/ethnic disparities in advanced‐stage breast cancer at diagnosis.

METHODS:

The authors used linked Surveillance, Epidemiology, and End Results‐Medicare data to determine whether comorbidity burden and comorbidity‐related care are associated with stage at diagnosis, whether these associations are mediated by mammography use, and whether they explain racial/ethnic disparities. Stage at diagnosis and mammography use were analyzed in multivariate regression models, adjusting for comorbidity burden and comorbidity‐race interactions among 118,742 women diagnosed with breast cancer during 1993 to 2005.

RESULTS:

Mammography utilization was higher among women with ≥3 stable comorbidities than among those without comorbidities. Advanced stage at diagnosis was associated with black race (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6‐1.8), Hispanic ethnicity (OR, 1.3; 95% CI, 1.2‐1.5), unstable comorbidity, and age ≥80 years. Mammography was protective in all racial/ethnic groups, but neither mammography use (OR, 0.3; 95% CI, 0.3‐0.3 and OR, 0.2; 95% CI, 0.2‐0.2 for women with 1 and ≥2 prior mammograms, respectively) nor overall physician service use (OR, 0.7; 95% CI, 0.7‐0.8 for women with ≥16 visits) explained the association between race/ethnicity and stage at diagnosis. The black/white OR fell to 1.2 (95% CI, 0.9‐1.5) among women with multiple stable comorbidities who received ≥2 screening mammograms, and 1.0 (95% CI, 0.8‐1.3) among mammography users with unstable comorbidities.

CONCLUSIONS:

Comorbidity burden was associated with regular mammography and earlier stage at diagnosis. Racial/ethnic disparities in late stage disease were reduced among women who received both regular mammograms and comorbidity‐related care. Cancer 2011. © 2011 American Cancer Society.     

Changes in functional status associated with radiation for prostate cancer in older veterans

BackgroundAlthough older men value maintaining independence and avoiding functional decline, little is known about their functional trajectories with receipt of prostate radiation.MethodsWe performed a retrospective cohort study including veterans age 65+ with localized prostate cancer who resided in a VA nursing facility while receiving prostate radiation from 2005 to 2015. We evaluated the change in Minimum Data Set (MDS) activities of daily living (ADL) score during 6 months from the start of treatment. Because prior studies have shown Charlson Comorbidity Index (CCI) to be a strong predictor of treatment-related toxicity, analysis included interaction with CCI.ResultsWe identified 487 patients with median age 73 (range 65–94). For the average patient in our cohort, the predicted MDS-ADL score worsened from 2.9 (95% CI 2.4–3.6) at the start of radiation to 3.8 (95% CI 3.1–4.8) at 3 months and then 4.5 (95% CI 3.5–5.7) at month 6. Patients with greater comorbidity (CCI ≥ 4) had worse functional outcomes in months 0–3 compared to patients with less comorbidity (CCI 0–3). MDS-ADL score worsened by 1.9 in the CCI ≥4 patients compared to 0.3 in the CCI 0–3 group During months 3–6, patients in both Charlson groups experienced similar worsening of MDS-ADL score.ConclusionsIn a vulnerable population of older patients with localized prostate cancer, radiation was associated with a decline in functional independence. Patients with higher comorbidity experienced more severe functional decline within the first 3 months of radiation therapy. In all comorbidity levels, functional status had not returned to baseline by 6 months.     

Assessing the impact of comorbid illnesses on death within 10 years in prostate cancer treatment candidates

BACKGROUND:

Treatment choice in prostate cancer is influenced by pre‐existing comorbid illnesses, but information about their individual prognostic impact is sparse, and only 1 comorbidity index has been developed for this setting. The authors assessed the impact of individual comorbid illnesses on the risk of early, other‐cause death in prostate cancer treatment candidates and propose a modification of an existing comorbidity scale.

METHODS:

A population‐based case‐cohort study included patients diagnosed from 1990 through 1998 in Ontario, Canada who had planned curative radiotherapy or prostatectomy. The subcohort numbered 1643, and the case sample (those dying of other causes within 10 years) numbered 630. Ontario Cancer Registry data were linked to data from medical charts, including: age, comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS‐G), stage, prostate‐specific antigen, Gleason score, and treatment. Cox proportional hazards regression assessed the age‐adjusted association between CIRS‐G and other‐cause death.

RESULTS:

Respiratory and cardiac diseases were the most common comorbidities and most strongly associated with an increased risk of death. Other important comorbidities included vascular disease, renal disease, and diabetes. The modified CIRS‐G_pros score yielded a relative risk (RR) of 1.64 (95% confidence interval [CI], 1.52–1.76) for those scoring 1 compared with 0 and RR 1.18 (95% CI, 1.15–1.21) for each increment above 1. Except for those aged >80 years, results were consistent across treatment type and age group.

CONCLUSIONS:

This study provides estimates of the role of individual comorbid illnesses in prostate cancer. The modified CIRS‐G_pros could be useful in the clinic and in future research on this patient population. Cancer 2011;. © 2011 American Cancer Society.     

Association between exercise and primary incidence of prostate cancer

BACKGROUND:

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men.

METHODS:

Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self‐reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self‐reported race.

RESULTS:

There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22‐0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models.

CONCLUSIONS:

In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race‐specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. Cancer 2013. © 2013 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.     

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

BACKGROUND.

It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006.

METHODS.

All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n = 6214) or unexposed (n = 6930) to Agent Orange. Strata‐specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate‐specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi‐square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression.

RESULTS.

Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75‐2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31‐3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange‐exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9‐60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8‐63.6 years), had a 2‐fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%‐27%) compared with unexposed men (10.5%; 95% CI, 5%‐15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%‐17.7%) than unexposed men (4%; 95% CI, 0.5%‐7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high‐grade and metastatic disease on presentation.

CONCLUSIONS.

Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as ‘high risk,’ just like men of African‐American heritage and men with a family history of prostate cancer. Cancer 2008. © 2008 American Cancer Society.     

Survival after hepatic resection of colorectal cancer metastases

BACKGROUND:

Most estimates of short‐ and long‐term survival after hepatic resection of colorectal cancer metastases are derived from surgical case series. For the current report, the authors used Medicare data to investigate operative mortality and long‐term survival in a national sample and examined the factors associated with survival.

METHODS:

Data were analyzed from Medicare enrollees (age ≥65 years) who were admitted to hospital between January 1, 2000 and December 31, 2004 with a primary diagnosis of colorectal cancer with resection. The sample was restricted to patients who subsequently underwent hepatic resection for liver metastases. The Medicare Denominator File was used to determine operative mortality and long‐term survival and the factors that were associated with those outcomes.

RESULTS:

Of the 306,061 Medicare beneficiaries who were diagnosed with colorectal cancer, 3957 patients were identified who underwent hepatic resection for liver metastases. The crude 30‐day and 90‐day mortality rates were 4% and 8.2%, respectively, and the 5‐year survival rate was 25.5%. Advancing age (hazards ratio [HR], 1.83; 95% confidence interval [95% CI], 1.32‐2.53 for age ≥80 years vs ages 65‐69 years), comorbid disease (HR, 1.40; 95% CI, 1.06‐1.85 for Charlson ≥5 vs Charlson 0), and synchronous colon/hepatic resection (HR, 2.46; 95% CI, 1.89‐3.20 for synchronous vs metachronous resection) were associated with worse 90‐day mortality. Similarly, long‐term mortality was associated with age (HR, 1.36; 95% CI, 1.18‐1.56), comorbid disease (HR, 1.51; 95% CI, 1.36‐1.69), and synchronous colon/hepatic resection (HR, 1.37; 95% CI, 1.24‐1.51 for synchronous vs metachronous resection).

CONCLUSIONS:

In this national study, short‐ and long‐term survival was worse than that reported in surgical case series. Subgroups at high risk for worse outcomes include the extreme elderly and those undergoing synchronous colon and hepatic resection. Cancer 2009. © 2009 American Cancer Society.     

Prospective study on metabolic factors and risk of prostate cancer

BACKGROUND:

There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

METHODS:

In the Metabolic Syndrome and Cancer Project (Me‐Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

RESULTS:

During a mean follow‐up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62‐1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74‐1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08‐1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07‐2.45); and per 1‐unit increase of the composite z score: RR, 1.13 (95% CI, 1.03‐1.25).

CONCLUSIONS:

The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. Cancer 2012. © 2012 American Cancer Society.