Statin medication use and the risk of biochemical recurrence after radical prostatectomy

BACKGROUND:

Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate‐specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).

METHODS:

The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.

RESULTS:

In total, 236 (18%) men were taking statins at RP. Median follow‐up was 24 months for statin users and 38 for nonusers. Statin users were older (P < .001) and underwent RP more recently (P < .001). Statin users were diagnosed at lower clinical stages (P = .009) and with lower PSA levels (P = .04). However, statin users tended to have higher biopsy Gleason scores (P = .002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio “HR”, 0.70; 95% confidence interval “CI”, 0.50‐0.97; P = .03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66‐1.73; P = .78; dose equivalent = simvastatin 20 mg: HR, 0.57; 95% CI, 0.32‐1.00; P = .05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27‐0.93; P = .03).

CONCLUSIONS:

In this cohort of men undergoing RP, statin use was associated with a dose‐dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. 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.     

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.     

Long‐term adverse effects after retropubic and robot‐assisted radical prostatectomy. Nationwide,population‐based study

Background and Objectives

Surgery for prostate cancer is associated with adverse effects. We studied long‐term risk of adverse effects after retropubic (RRP) and robot‐assisted radical prostatectomy (RARP).

Methods

In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.

Results

A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42‐0.63) and RR for procedures 0.46 (95%CI = 0.38‐0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01‐2.16), and RR for procedures 1.52 (95%CI = 1.02‐2.26).

Conclusions

The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.     

Is delayed radical prostatectomy in men with low‐risk screen‐detected prostate cancer associated with a higher risk of unfavorable outcomes?

BACKGROUND:

Strategies of active surveillance (AS) of low‐risk screen‐detected prostate cancer have emerged, because the balance between survival outcomes and quality of life issues when radically treating these malignancies is disputable. Delay before radical treatment caused by active surveillance may be associated with an impaired chance of curability.

METHODS:

Men diagnosed with low‐risk (T1c/T2; prostate‐specific antigen [PSA] = <10.0; PSA density, <0.2 ng/mL; Gleason score, 3 + 3=6; 1‐2 positive biopsies) prostate cancer in the Swedish section of the European Randomized Study of Screening for Prostate Cancer who received radical prostatectomy (RP) were studied. One group received immediate RP, whereas another group received delayed RP after an initial period of expectant management. These groups were compared regarding histopathological and biochemical outcomes, correcting for baseline differences.

RESULTS:

Mean follow‐up after diagnosis was 5.7 years (standard deviation [SD], 3.2). The immediate RP group (n = 158) received RP a mean of 0.5 (SD, 0.2) years after diagnosis; the delayed RP group (n = 69) received RP after 2.6 (SD, 2.0) years (P < .001). After adjustment for small baseline dissimilarities, no differences in RP frequencies of Gleason score >6 (odds ratio [OR], 1.54; P = .221), capsular penetration (OR, 2.45; P = .091), positive margins (OR, 1.34; P = .445), RP tumor volume (difference, 0.099; P = .155), or biochemical progression rates (P = .185, P = .689) were found between groups, although all data were in favor of immediate RP.

CONCLUSIONS:

With limited patient numbers available for analysis, differences in intermediate outcomes between immediate RP and delayed RP were nonsignificant. The delayed RP group may be subject to a selection bias. Prospective evaluation of active surveillance protocols is essential. Cancer 2010. © 2010 American Cancer Society.     

Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated prostate‐specific antigen

BACKGROUND:

Risk models to predict prostate cancer on biopsy, whether they include only prostate‐specific antigen (PSA) or other markers, are intended for use in all men of screening age. However, the association between PSA and cancer probably depends on a man's recent screening history.

METHODS:

The authors examined the effect of prior screening on the ability to predict the risk of prostate cancer by using a previously reported, 4‐kallikrein panel that included total PSA, free PSA, intact PSA, and human kallikrein‐related peptidase 2 (hK2). The study cohort comprised 1241 men in Gothenburg, Sweden who underwent biopsy for elevated PSA during their second or later visit for the European Randomized Study of Screening for Prostate Cancer. The predictive accuracy of the 4‐kallikrein panel was calculated.

RESULTS:

Total PSA was not predictive of prostate cancer. The previously published 4‐kallikrein model increased predictive accuracy compared with total PSA and age alone (area under the curve [AUC], 0.66 vs 0.51; P < .001) but was poorly calibrated and missed many cancers. A model that was developed with recently screened men provided important improvements in discrimination (AUC, 0.67 vs 0.56; P < .001). Using this model reduced the number of biopsies by 413 per 1000 men with elevated PSA, missed 60 of 216 low‐grade cancers (Gleason score ≤6), but missed only 1 of 43 high‐grade cancers.

CONCLUSIONS:

Previous participation in PSA screening dramatically changed the performance of statistical models that were designed to predict biopsy outcome. A 4‐kallikrein panel was able to predict prostate cancer in men who had a recent screening history and provided independent confirmation that multiple kallikrein forms contribute important diagnostic information for men with elevated PSA. Cancer 2010. © 2010 American Cancer Society.     

Short- vs long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate

BACKGROUND

The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high‐risk prostate cancer was associated with prolonged survival in advanced age men.

METHODS

A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high‐grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow‐up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred.

RESULTS

Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1; 95% confidence interval [CI]: 0.7, 1.8; P = .70), whereas age at randomization (AHR: 1.05; 95% CI: 1.01, 1.09; P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6; 95% CI: 0.9, 2.6; P = .09).

CONCLUSIONS

After adjusting for known prognostic factors, the treatment of node‐negative, high‐risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study. Cancer 2007. © 2007 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.     

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands

Background:

Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA.

Methods:

The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (⩾3 ng ml⁻¹), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy.

Results:

The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason ⩾7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less.

Conclusions:

Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.     

Prostate‐specific antigen screening for prostate cancer and the risk of overt metastatic disease at presentation

BACKGROUND:

The objective of this study was to estimate the total number of patients who would be expected to present with metastatic (M1) prostate cancer (PC) in the modern US population in a given year if the age‐specific and race‐specific annual incidence rates of M1 PC were the same as the rates in the era before prostate‐specific antigen (PSA) testing.

METHODS:

The authors computed the total number of men who presented with M1 PC in the Surveillance, Epidemiology, and End Results (SEER) 9 registries area in the year 2008 (the most recent SEER year) and estimated the number of cases that would be expected to occur in this area in the year 2008 in the absence of PSA testing. The expected number was computed by multiplying each age‐race–specific average annual incidence rate from the pre‐PSA era (1983‐1985) by the number of men in the corresponding age‐race category in the year 2008 and adding the products.

RESULTS:

In the year 2008, the observed and expected numbers of men presenting with M1 PC in the SEER 9 registries area were 739 and 2277, respectively, with an expected‐to‐observed ratio of 3.1 (95% confidence interval, 3.0‐3.2). If this ratio was applied to the total US population in the year 2008, then the total number of men presenting with M1 PC in that year would be equal to approximately 25,000 instead of the approximately 8000 actually observed.

CONCLUSIONS:

If the pre‐PSA era rates were present in the modern US population, then the total number of men presenting with M1 PC would be approximately 3 times greater than the number actually observed. Cancer 2012. © 2012 American Cancer Society.     

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors

BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. RESULTS: Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC.     

Impact of race on biochemical disease recurrence after prostate brachytherapy

BACKGROUND:

Understanding racial differences in disease presentation and response to therapy is necessary for the effective treatment and control of prostate cancer. In this study, the authors examined the influence of race on biochemical disease‐free survival (BDFS) among men who received prostate brachytherapy.

METHODS:

In total, 2301 men were identified who had a minimum follow‐up of 24 months and had received low‐dose‐rate brachytherapy for prostate cancer at the Mount Sinai Medical Center from June 1990 to October 2008. Patient factors, with specific emphasis on patient race, were analyzed with respect to freedom from biochemical failure (FFbF). Kaplan‐Meier analyses, life‐tables, and log‐rank tests were used to identify variables that were predictive of 10‐year FFbF.

RESULTS:

In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10‐year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10‐year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10‐year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10‐year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate‐specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low‐risk disease, the 10‐year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10‐year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen‐deprivation therapy(ADT) with or without supplemental external‐beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10‐year FFbF. No significant differences was observed in overall survival, cause‐specific survival, or distant metastasis‐free survival between racial groups.

CONCLUSIONS:

AA race appeared to be an independent negative predictor of BDFS after prostate brachytherapy, and this result may highlight the need for more aggressive therapy in this patient population. Cancer 2011;. © 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.     

Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials

BACKGROUND:

Several phase II trials in men with noncastrate PSA‐recurrent prostate cancer have assessed the impact of novel nonhormonal agents on PSA kinetics. However, it is unknown whether changes in PSA kinetics influence metastasis‐free survival (MFS).

METHODS:

We performed a retrospective post hoc analysis of 146 men treated in 4 phase II trials examining the investigational agents marimastat (a matrix metalloproteinase inhibitor; n = 39), imatinib (a tyrosine kinase inhibitor; n = 25), ATN‐224 (a copper/zinc‐superoxide dismutase inhibitor; n = 22), and lenalidomide (an antiangiogenic/immunomodulatory drug; n = 60). We investigated factors influencing MFS, including within‐subject changes in PSA kinetics (PSA slope, doubling time, and velocity) before and after treatment initiation.

RESULTS:

After a median follow‐up of 16.8 months, 70 patients (47.9%) developed metastases. In multivariable Cox regression models, factors that were independently predictive of MFS after adjusting for age and other clinical prognostic variables were baseline PSA doubling time (PSADT) (P = .05), baseline PSA slope (P = .01), on‐study change in PSADT (P = .02), and on‐study change in PSA slope (P = .03). In a landmark Kaplan‐Meier analysis, median MFS was 63.5 months (95% confidence interval [CI], 34.6‐not reached) and 28.9 months (95% CI, 13.5‐68.0) for men with or without any decrease in PSA slope by 6 months after treatment, respectively.

CONCLUSIONS:

This hypothesis‐generating analysis suggests that within‐subject changes in PSADT and PSA slope after initiation of experimental therapy may correlate with MFS in men with biochemically recurrent prostate cancer. If validated in prospective trials, changes in PSA kinetics may represent a reasonable intermediate end point for screening new agents in these patients. Cancer 2011;. © 2011 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.     

Disparities in prostate cancer screening,diagnoses, management,and outcomes between Indigenous and non-Indigenous men in a universal health care system

Background

Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought.

Methods

An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals.

Results

Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50–70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25–65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2–4.2; p < .01) than non-Indigenous men.

Conclusions

Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.     

Hormonal therapy or external-beam radiation with brachytherapy and the risk of death from prostate cancer in men with intermediate risk prostate cancer

Purpose

To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy.

Patients and Methods

A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer-specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category.

Results

Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively).

Conclusion

Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.     

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.     

Circulating estradiol, but not testosterone, is a significant predictor of high-grade prostate cancer in patients undergoing radical prostatectomy

BACKGROUND:

The objective of this study was to assess the association between preoperative circulating levels of 17β‐estradiol (E₂) and high‐grade prostate cancer (HGPCa) (Gleason grade ≥4 + 3) at the time patients underwent radical retropubic prostatectomy (RRP).

METHODS:

Serum total testosterone (tT), sex hormone‐binding globulin (SHBG), and E₂ levels were measured the day before surgery (8‐10 AM ) in a cohort of 655 consecutive Caucasian‐ European patients who underwent RRP at a single institution. Logistic regression models were used to test the association between predictors (including age, body mass index, prostate‐specific antigen [PSA], clinical tumor classification, biopsy Gleason sum, tT, SHBG, and E₂) and HGPCa. Serum E₂ was included in the model as both a continuous variable and a categorized variable (according to the most informative cutoff: 50 pg/mL).

RESULTS:

Pathologic HGPCa was identified in 156 patients (23.8%). Patients with HGPCa had significantly higher PSA, clinical tumor classification, and biopsy Gleason sum than those without HGPCa (all P < .001). No other significant differences were observed between groups. At univariate analysis, continuously coded E₂ was not associated significantly with HGPCa (odds ratio [OR], 1.009; P = .25), whereas patients with E₂ levels ≥50 pg/mL had a 3.24‐fold increased risk of HGPCa (P < .001). At multivariate analysis, E₂ was associated significantly with HGPCa both as a continuous predictor (OR, 1.02; P = .04) and as a categorical predictor (OR, 3.94; P < .001) after accounting for other variables. Conversely, tT and SHBG levels were not associated significantly with HGPCa.

CONCLUSIONS:

E₂ was associated significantly with pathologic HGPCa, whereas SHBG and tT failed to demonstrate any association with HGPCa in patients who underwent RRP. Cancer 2011;. © 2011 American Cancer Society.     

Outcomes after prostate brachytherapy are even better than predicted

BACKGROUND:

During the first 3 years after prostate cancer treatment with radiation therapy, benign prostate‐specific antigen (PSA) bounces are difficult for clinicians to distinguish from a biochemical recurrence, which can result in unnecessary interventions and erroneous predictions of outcomes. The objective of this study was to evaluate a commonly used PSA failure definition in a multinational, multi‐institutional study after monotherapy with prostate brachytherapy.

METHODS:

Participants were selected from 2919 men who underwent permanent prostate brachytherapy at the University Medical Center Utrecht, Princess Margaret Hospital, or Seattle Prostate Institute between 1998 and 2006. Inclusion required not having received androgen‐deprivation therapy and having at least 30 months of follow‐up. Failure was defined as any post‐treatment use of hormone therapy, clinical relapse, or prostogram‐defined biochemical (PSA) failure. Cases in which the nomogram predicted biochemical failure were evaluated at each institution to verify biochemical status over time and the actual clinical outcome at 5 years.

RESULTS:

The median follow‐up for the 1816 patients was 5.2 years. Concordance between the prostogram‐predicted and actual outcomes, as measured by the Harrell c statistic, was 0.655 (95% confidence interval [CI], 0.536‐0.774; P = .010) for the Princess Margaret group, 0.493 (95% CI, 0.259‐0.648; P = .955) for the Seattle group, and 0.696 (95% CI, 0.648‐0.744, P < .001) for the Utrecht group. The overall mean difference in biochemical recurrence‐free survival at 5 years between actual outcomes and prostogram‐defined outcomes was 9.2% (95% CI, 7.7%‐10.6%). The total numbers of prostogram‐defined and actual biochemical failures were 312 and 157, respectively (P = .001).

CONCLUSIONS:

The widely used prostogram could not adequately distinguish a benign PSA bounce from a biochemical recurrence after prostate brachytherapy and could not be used to counsel patients about their predicted outcomes after treatment. The authors conclude that, to avoid unnecessary active interventions after treatment, clinicians should monitor PSA levels for at least 3 years and provide reassurance to patients that a PSA rise during this time is common and may not indicate a treatment failure. Cancer 2012;118:839–847. © 2011 American Cancer Society.