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.     

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.     

Androgen deprivation and thromboembolic events in men with prostate cancer

BACKGROUND:

Androgen deprivation therapy (ADT) improves prostate cancer outcomes in specific clinical settings, but is associated with adverse effects, including cardiac complications and possibly thromboembolic complications. The objective of this study was to estimate the impact of ADT on thromboembolic events (TEs) in a population‐based cohort.

METHODS:

In the linked Surveillance, Epidemiology and End Results–Medicare database, we identified men older than 65 who were diagnosed with nonmetastatic prostate cancer between 1999 and 2005. Medical or surgical ADT was identified by Medicare claims for gonadotropin‐releasing hormone agonists or bilateral orchiectomy at any time following diagnosis. TEs included deep venous thrombosis, pulmonary embolism, and arterial embolism. The impact of ADT on the risk of any TE and on total number of events was estimated, controlling for patient and tumor characteristics.

RESULTS:

Of 154,611 patients with prostate cancer, 58,466 (38%) received ADT. During a median follow‐up of 52 months, 15,950 men had at least 1 TE, including 8829 (55%) who had ADT and 7121 (45%) with no ADT. ADT was associated with increased risk of a TE (adjusted hazard ratio = 1.56; 95% confidence interval, 1.50‐1.61; P < .0001), and duration of ADT was associated with the total number of events (P < .0001).

CONCLUSIONS:

In this population‐based cohort, ADT was associated with increased risk of a TE, and longer durations of ADT were associated with more TEs. Men with intermediate‐ and low‐risk prostate cancer should be assessed for TE risk factors before starting ADT and counseled regarding the risks and benefits of this therapy. Cancer 2011. © 2011 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.     

Limits of observational data in determining outcomes from cancer therapy

BACKGROUND.

Observational data are used increasingly to assess the effectiveness of therapies. However, selection biases are likely to have an impact on results and threaten the validity of these studies.

METHODS.

The primary objective of the current study was to explore the effect of selection biases in observational studies of treatment effectiveness in cancer care. Patients were identified from the Surveillance, Epidemiology, and End Results‐Medicare linked database. The following groups of patients were included: 5245 men treated with and without androgen deprivation for locally advanced prostate cancer, 43,847 men with active treatment versus observation for low‐ and intermediate‐risk prostate cancer, and 4860 patients with lymph node‐positive colon cancer who were treated with and without fluorouracil chemotherapy. Patients were compared by therapy for the outcomes of cancer‐specific mortality, other‐cause mortality, and overall mortality.

RESULTS.

In all comparisons, the observational data produced improbable results. For example, when evaluating outcomes of men who were treated with and without androgen deprivation for locally advanced prostate cancer, men who underwent androgen deprivation had higher prostate cancer mortality (hazard ratio, 1.5; 95% confidence interval, 1.29–1.92) despite clinical trial evidence that this treatment improves cancer mortality. Controlling for comorbidity, extent of disease, and other characteristics by multivariate analyses or by propensity analyses had remarkably small impact on these improbable results.

CONCLUSIONS.

The current results suggested that the results from observational studies of treatment outcomes should be viewed with caution. Cancer 2008. © 2008 American Cancer Society.     

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.     

Risk of dying from prostate cancer in men randomized to screening

BACKGROUND:

Although the true benefits and disadvantages of prostate cancer screening are still not known, the analysis of fatal cases is important for increasing knowledge of the effects of prostate cancer screening on mortality. Who dies from prostate cancer despite participation in a population‐based prostate‐specific antigen (PSA) screening program?

METHODS:

From the Goteborg branch of the European Randomized study of Screening for Prostate Cancer, 10,000 men randomly assigned to active PSA‐screening every second year formed the basis of the present study. Prostate cancer mortality was attributed to whether the men were attendees in the screening program (attending at least once) or nonattendees.

RESULTS:

Thirty‐nine men died from prostate cancer during the first 13 years. Both overall (34% vs 13 %; P < .0001) and cancer‐specific mortality (0.8% vs 0.3 %; P < .005) were found to be significantly higher among nonattendees compared with attendees. Furthermore, the majority of deaths (12 of 18) among screening attendees were in men diagnosed at first screening (prevalent cases). Only 6 deaths (including 3 interval cases) were noted among men complying with the biennial screening program.

CONCLUSIONS:

Nonattendees in prostate cancer screening constitute a high‐risk group for both death from prostate cancer and death from other causes comparable to that described in other cancer screening programs. Cancer 2009. © 2009 American Cancer Society.     

Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer

BACKGROUND.

The objective of this study was to report the rates of disease‐free survival (DFS), cause‐specific survival (CSS), and overall survival after low‐dose‐rate (LDR) prostate brachytherapy (PB).

METHODS.

Data from 1006 consecutive patients with prostate cancer who received LDR‐PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low‐risk (58%) or intermediate‐risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty‐five percent of patients received 3 months of neoadjuvant androgen‐deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables.

RESULTS.

The median follow‐up was 7.5 years. By using Fine and Gray competing risks analysis, the 5‐year and 10‐year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%‐97.7%) and 94.1% (95% confidence interval, 92%‐95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10‐year CSS rate was 99.1% (95% confidence interval, 97.3%‐99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%‐95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%‐86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis.

CONCLUSIONS.

In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low‐risk and intermediate‐risk prostate cancer, the actuarial rate of recurrent disease after LDR‐PB was approximately 3% at 5 years and 6% at 10 years. Cancer 2013. © 2012 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.     

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.     

How can we make cancer survival statistics more useful for patients and clinicians: An illustration using localized prostate cancer in Sweden

Purpose

Studies of cancer patient survival typically report relative survival or cause-specific survival using data from patients diagnosed many years in the past. From a risk-communication perspective, such measures are suboptimal for several reasons; their interpretation is not transparent for non-specialists, competing causes of death are ignored and the estimates are unsuitable to predict the outcome of newly diagnosed patients. In this paper, we discuss the relative merits of recently developed alternatives to traditionally reported measures of cancer patient survival.

Methods

In a relative survival framework, using a period approach, we estimated probabilities of death in the presence of competing risks. To illustrate the methods, we present estimates of survival among 23,353 initially untreated, or hormonally treated men with intermediate- or high-risk localized prostate cancer using Swedish population-based data.

Results

Among all groups of newly diagnosed patients, the probability of dying from prostate cancer, accounting for competing risks, was lower compared to the corresponding estimates where competing risks were ignored. Accounting for competing deaths was particularly important for patients aged more than 70 years at diagnosis in order to avoid overestimating the risk of dying from prostate cancer.

Conclusions

We argue that period estimates of survival, accounting for competing risks, provide the tools to communicate the actual risk that cancer patients, diagnosed today, face to die from their disease. Such measures should offer a more useful basis for risk communication between patients and clinicians and we advocate their use as means to answer prognostic questions.     

Predictors of competing mortality in early breast cancer

BACKGROUND:

Death in the absence of disease recurrence (competing mortality) is an important determinant of disease‐free survival (DFS) in early breast cancer. The authors sought to identify predictors of this event using competing risks modeling.

METHODS:

A cohort study was made of 1231 consecutive women with stage I to II invasive breast cancer diagnosed between 1986 and 2004, treated with breast conservation therapy. Median follow‐up was 82 months. The authors used a parametric competing risks regression model to analyze factors associated with the cumulative incidence of competing mortality. They generated a risk score from the model coefficient estimates and stratified patients according to low and high risk score for analysis.

RESULTS:

Ten‐year DFS was 69.7% (95% confidence interval [CI], 66.2%‐72.9%). The 10‐year cumulative incidence of locoregional recurrence (LRR) was 4.4% (95% CI, 3.0%‐5.8%), distant recurrence was 7.1% (95% CI, 5.4%‐8.9%), and competing mortality was 18.7% (95% CI, 15.9%‐21.6%). On multivariate analysis, competing mortality was associated with increasing age (hazard ratio [HR], 1.83 per 10 years; 95% CI, 1.58‐2.12), black race (HR, 1.71; 95% CI, 1.17‐2.51), and comorbid disease (HR, 1.93, 95% CI, 1.40‐2.65). Ten‐year cumulative incidences of competing mortality, locoregional recurrence, and distant recurrence for patients at low (n = 638) versus high (n = 593) risk of competing mortality were 7.2% versus 30.6% (P < .001), 4.4% versus 4.4% (P = .97), and 8.6% versus 5.6% (P = .12), respectively.

CONCLUSIONS:

Competing mortality is an important event influencing 10‐year DFS in early breast cancer and is associated with increasing age, black race, and comorbid disease. Stratifying patients according to competing mortality risk may be useful in designing clinical trials. Cancer 2010. © 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.     

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.     

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. Cancer 2011. © 2010 American Cancer Society.     

Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade

Background

Higher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading.

Methods

We characterized vessel morphology (area and irregularity) among 511 patients diagnosed with prostate cancer during 1986 to 2000, re-reviewed Gleason grade, and followed men through 2012. Men were grouped according to integrated vessel lumen irregularity and vessel area across Gleason grade. The more angiogenic group was identified as those with more irregular vessel lumen and smaller vessel area. Crude rates (95 % confidence intervals) and survival probability were estimated across Gleason grade and vessel morphology.

Results

During a median 14-year follow-up, 62 men developed bone metastases or died of prostate cancer. Lethality rates were uniformly low within Gleason grade categories 6 and 7(3 + 4), regardless of vessel morphology. However, among men with Gleason grades of 7(4 + 3) or 8–10, the more angiogenic group was associated with fourfold higher risk of lethal outcomes compared to those with less angiogenic potential. Ten-year survival probability ranged from 95 to 74 % according to the extent of vessel morphology (p < 0.0001, log-rank test).

Conclusions

Vessel morphology may aid Gleason grading in predicting prostate cancer mortality risks among men diagnosed with high-grade Gleason cancers.

     

Dairy intake after prostate cancer diagnosis in relation to disease‐specific and total mortality

Information regarding postdiagnostic dairy intake and prostate cancer survival is limited. We evaluated intake of total, high‐fat and low‐fat dairy after prostate cancer diagnosis in relation to disease‐specific and total mortality. We included 926 men from the Physicians’ Health Study diagnosed with non‐metastatic prostate cancer between 1982 and 2000 who completed a diet questionnaire a median of 5 years after diagnosis and were followed thereafter for a median of 10 years to assess mortality. Cox proportional hazards regression was used to estimate associations between dairy intake and prostate cancer specific and all‐cause mortality. During 8,903 person‐years of follow‐up, 333 men died, 56 due to prostate cancer. Men consuming ≥3 servings/day of total dairy products had a 76% higher risk of total mortality and a 141% higher risk of prostate cancer‐specific mortality compared to men who consumed less than 1 dairy product/day (hazard ratio (HR) = 1.76, 95% confidence interval (CI): 1.21, 2.55, p_trend < 0.001 for total mortality; HR = 2.41, 95% CI: 0.96, 6.02, p_trend = 0.04 for prostate cancer‐specific mortality). The association between high‐fat dairy and mortality risk appeared to be stronger than that of low‐fat dairy, but the difference between them was not statistically significant (p for difference = 0.57 for prostate cancer‐specific mortality and 0.56 for total mortality). Among men without metastases when diagnosed, higher intake of dairy foods after prostate cancer diagnosis may be associated with increased prostate cancer‐specific and all‐cause mortality.     

Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort

BACKGROUND: Prostate cancer tends to affect older men and to progress relatively slowly. Since the prevalence of comorbidity increases with advancing age, competing causes of death are important contributors to death rates among prostate cancer patients. Accurate determination of the underlying causes of death in older men dying with prostate cancer may thus also be more difficult. METHODS: We compared the distribution of underlying causes of death in decedents from a population-based cohort of elderly prostate cancer patients to that from a population-based comparison cohort of elderly men without prostate cancer. Among decedents from the prostate cancer patient cohort, we examined associations of patient demographics, disease stage, and initial treatment, with assignment of a prostate cancer underlying cause of death (versus any other cause) by use of multivariable logistic regression. In the subgroup of prostate cancer patient decedents having underlying causes of death other than prostate cancer, the underlying cause distribution was compared with that in nonprostate cancer cohort decedents. RESULTS: Prostate cancer was the underlying cause for 39% (95% confidence interval [CI] = 36.3-41.9) of the decedents in the prostate cancer cohort. Causes of death among prostate cancer patients not dying of prostate cancer were similar to those among the nonprostate cancer cohort decedents. However, in those who were aggressively treated, the adjusted odds of other cancer causes of death were 51% higher (odds ratio [OR] = 1.51; 95% CI = 1.08-2.10) than that in nonprostate cancer patient decedents, while in those treated with watchful waiting the adjusted odds were 34% lower (OR = 0.66; 95% CI = 0.47-0.93). CONCLUSIONS: Initial treatment may influence the underlying cause of death reported in vital statistics for prostate cancer patients.     

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.     

Post‐diagnosis alcohol intake and prostate cancer survival: A population‐based cohort study

Alcohol consumption has been declared a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) and is a potential risk factor for several types of cancer mortality. However, evidence for an association with prostate cancer survival remains inconsistent. We examined how alcohol consumption post‐diagnosis was associated with survival after prostate cancer diagnosis. Men diagnosed with prostate cancer (n = 829) in Alberta, Canada between the years 1997 and 2000 were recruited into a population‐based case–control study and then followed for up to 19 years for survival outcomes. Pre‐ and post‐diagnosis alcohol consumption, clinical characteristics and lifestyle factors were collected through in‐person interviews shortly after diagnosis and again 2–3 years post‐diagnosis. Cox proportional hazards were used to examine how post‐diagnosis alcohol consumption was associated with all‐cause and prostate cancer‐specific mortality (competing risk analysis too), in addition to first recurrence/progression or new primary cancer. Most participants reported drinking alcohol (≥once a month for 6 months) post‐diagnosis (n = 589, 71.0%). Exceeding Canadian Cancer Society (CCS) alcohol consumption recommendations (≥2 drinks/day) post‐diagnosis was associated with prostate cancer‐specific mortality relative to non‐drinkers (aHR: 1.82, 95% CI: 1.07–3.10) with borderline evidence of a linear trend. Interestingly, those in the highest quartile of drinks/week pre‐ and post‐diagnosis also had a twofold increase for prostate‐specific mortality (aHR: 2.67, 95% CI: 1.28–5.56) while controlling for competing risks. Our results support post‐diagnosis alcohol consumption was associated with increased mortality after prostate cancer diagnosis, specifically for prostate cancer‐related death. Future studies focused on confirming this burden of disease are warranted.