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Study Type – Prognosis (inception cohort) Level of Evidence 1b OBJECTIVE To evaluate the relationship between testosterone levels and the development of high-risk prostate cancer, by prospectively examining serum androgen concentrations in a well-studied cohort, as the role of testosterone in prostate cancer progression is debated. PATIENTS AND METHODS The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of ≥20 ng/mL at diagnosis, or a Gleason score of ≥8. The hazard ratio (HR) of high-risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses. RESULTS The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95% confidence interval, CI, 1.01–4.23; P = 0.047); the likelihood for men aged ≤65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35–2.6; P = 0.9). The risk rate per person-years increased from lowest to highest tercile of FTI for the oldest men (age >70 years) but this trend was not apparent among younger men. CONCLUSION Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone-replacement therapy. [ABSTRACT FROM AUTHOR]

Purpose: According to a 1944 publication by Swyer benign prostatic hyperplasia develops in some men after age 45 with further prostatic growth whereas in other men prostate size remains stable or decreases with advancing age. Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia, less is known about the phenomenon of prostate atrophy. Materials and Methods: In the Baltimore Longitudinal Study of Aging serial pelvic magnetic resonance imaging was performed in men without prostate cancer beginning in 1993. From this population we retrospectively identified 278 men with 2 or more magnetic resonance imaging determined prostate volume measurements to examine differential growth rates in a cohort of community men over time. Results: Median age was 58 years and median prostate size was 28 cc at study entry. At a median followup of 4.3 years prostate size increased in 61.9% and remained stable or decreased in 38.1% of men. The median rate of volume change was 0.6 cc per year (range −9.9 to 62.1), corresponding to a median growth rate of 2.5% per year (range −29.2 to 176.4%). During followup 64.6% of men with an initial prostate size less than 40 cc had prostate growth compared to only 50.9% of men with an initial prostate size of 40 cc or greater. Conclusions: These results suggest that changes in prostate size are highly variable among aging men. Although benign prostatic hyperplasia is common, a considerable proportion of aging men have a stable or decreasing prostate size. Further research is needed to identify the underlying mechanism for such differences in prostate growth. [Copyright &y& Elsevier]

Purpose: Prostate specific antigen is used for prostate cancer screening but its specificity is limited. Specificity might be increased by considering genotype associated prostate specific antigen levels. Materials and Methods: We examined associations between single nucleotide polymorphisms on chromosomes 10 and 19 (previously shown to be associated with prostate specific antigen) with prostate specific antigen and prostate cancer in 505 men from the Baltimore Longitudinal Study of Aging. Results: In a model with age and date the risk ratio for prostate cancer was 1.18 (95% CI 1.13–1.23) per unit increase in prostate specific antigen. Including the interaction between alleles and prostate specific antigen significantly altered the risk ratio for prostate cancer (Cox proportional hazards p <0.001). Specifically prostate cancer risk per unit increase in prostate specific antigen was significantly different in carriers than in noncarriers of a minor allele (1.28 vs 1.10, respectively, Cox proportional hazards p <0.001), whereas men with a minor allele had a significantly higher risk of prostate cancer at prostate specific antigen levels greater than 6 ng/ml. Conclusions: Our data suggest that genotype influences the risk of prostate cancer per unit increase in prostate specific antigen. Prostate cancer risk stratification using prostate specific antigen and genotype could improve prostate specific antigen test performance. [Copyright &y& Elsevier]

Purpose: Although prostate specific antigen velocity was proposed to increase the specificity of prostate specific antigen-based screening, there are little published data on the effect of differential prostate growth on prostate specific antigen velocity. If a patient presents with rising prostate specific antigen over a year or more, it would be useful to know whether such a change in prostate specific antigen could be explained by prostate growth. Thus, we investigated the relationship between changes in prostate size and prostate specific antigen changes in a large cohort of men without prostate cancer. Materials and Methods: We identified 242 men without prostate cancer from the Baltimore Longitudinal Study of Aging who had 2 or greater serial pelvic magnetic resonance imaging studies and contemporaneous prostate specific antigen measurements. In this population we used the t test, correlation coefficients, and regression analysis to examine the relationship between prostate specific antigen changes and prostate volume changes, as assessed by magnetic resonance imaging. Results: The mean age was 55 years. During 4.2 years of median followup, the median rate of volume change was 0.6 cc per year (range −9.9 to 11.8), and the median prostate specific antigen change was 0.03 ng/ml per year. There was no correlation between prostate specific antigen changes and prostate growth, as measured in cc per year (r = −0.01, p = 0.9) or the percent change per year (r = 0.07, p = 0.3). On multivariate analysis, there was no significant relationship between changes in prostate volume and prostate specific antigen changes. Conclusions: Our data suggest that volume increases alone do not cause a high prostate specific antigen velocity. Despite growth rates as high as 10 cc per year, prostate specific antigen velocity was less than 0.1 ng/ml per year in most men without prostate cancer. Thus, differential rates of prostatic growth should not confound the use of prostate specific antigen velocity for prostate cancer detection and prognostication. [Copyright &y& Elsevier]

Objectives: To describe the distribution and implications of prostate-specific antigen velocity (PSAV) by prostate-specific antigen (PSA) in an unselected population. A PSAV >0.35 and >2.0 ng/mL/y have been associated with an increased risk of prostate cancer (CaP) death more than 10 years and 1 year before diagnosis, respectively. It is unknown how frequently PSAVs of this magnitude occur in community men. Methods: From the Baltimore Longitudinal Study of Aging, we examined the PSAV distribution in 786 men with serial PSA measurements (3474 PSAV observations) at total PSA levels <10 ng/mL. We also determined whether PSAV altered the probability of overall and life-threatening CaP at PSA levels <3 and 3-10 ng/mL. Results: Overall, the mean PSA and PSAV were 1.3 ng/mL and 0.05 ng/mL/y, respectively. PSAV rose continuously with increasing PSA (P <.0001), and was significantly higher in cancers than controls for observations at PSA levels <3 ng/mL (P = .02) and 3-10 ng/mL (P = .0008). The probability of life-threatening CaP was 3% at a PSA <3 ng/mL, but increased to 13.6% with PSAV >0.4 ng/mL/y. At PSA levels of 3-10 ng/mL, the probability of life-threatening CaP was 9.8% based on PSA alone vs 12% with PSAV >0.4 ng/mL/y. Conclusions: PSAV was significantly higher in CaP observations than controls in all PSA ranges studied and altered the risk of overall and life-threatening CaP at a given PSA level. Because the value of PSAV is PSA-dependent, the PSA level should be taken into account when interpreting PSAV. [ABSTRACT FROM AUTHOR]

To compare the effects of a pedometer-based behavioral intervention (Fitness for Life [FFL] program) and a traditional high-intensity fitness (TRAD) program on physical activity (PA), Army Physical Fitness Test (APFT), and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run. From a pool of 261 Army National Guard, a total of 156 were randomized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance. For both groups, the total APFT score and 2-mile run time/score improved from baseline to 12 weeks (FFL: down 7.4%, p = 0.03; TRAD: down 5%, p = 0.08) but at 24 weeks they had regressed toward baseline. PA improved modestly and coronary risk profile changed minimally in both groups. A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA, APFT, and 2-mile run times/score. Neither group sustained the improved run times over the 12 weeks of maintenance.

Purpose: We updated our experience with a strategy of expectant treatment for men with stage T1c prostate cancer and evaluated predictors of disease intervention., Materials and Methods: A total of 407 men with a median age of 65.7 years (range 45.8 to 81.5) with stage T1c (99.8%) or T2a (0.2%) prostate cancer suspected of harboring small volume prostate cancer based on needle biopsy findings and prostate specific antigen density have been followed in a prospective, longitudinal surveillance program with a median followup of 2.8 years (range 0.4 to 12.5). A recommendation for treatment was made if disease progression was suggested by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer or greater than 50% involvement of any core with cancer). Cox proportional hazards regression was used to evaluate the affect of multiple covariates on the outcome of curative intervention., Results: Of 407 men 239 (59%) men remained on active surveillance at a median followup of 3.4 years (range 0.43 to 12.5), 103 (25%) underwent curative intervention at a median of 2.2 years after diagnosis (range 0.96 to 7.39) and 65 (16%) were either lost to followup (12), withdrew from the program (45), or died of causes other than prostate cancer (8). Older age at diagnosis (p = 0.011) and an earlier date of diagnosis (p = 0.001) were significantly associated with curative intervention., Conclusions: Recognizing that over treatment of prostate cancer is prevalent, especially among elderly patients, a program of careful selection and monitoring of older men who are likely to harbor small volume, low grade disease may be a rational alternative to the active treatment of all.