Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy.

OBJECTIVES: To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively. PARTICIPANTS AND METHODS: We performed a single-centre, randomised, double-blind, placebo-controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS. Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF-36 scores between both groups were compared using linear regression, adjusted for baseline scores. RESULTS: The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [sd] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within-group analysis showed a significant improvement in fatigue scores in the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo (P = 0.04 for both component scores). CONCLUSIONS: Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH-induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue.

Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort.

BACKGROUND: A biologic rationale exists for the association between metabolic syndrome (MetS) and prostate cancer (PCa). However, epidemiologic studies have been conflicting. OBJECTIVE: To evaluate the association between MetS and the odds of PCa diagnosis in men referred for biopsy. DESIGN, SETTING, AND PARTICIPANTS: Patients without prior PCa diagnosis undergoing prostate biopsy were identified from a large prostate biopsy cohort (in Toronto, Canada). The definition of MetS was based on the most recent interim joint consensus definition, requiring any three of five components (obesity, elevated blood pressure, diabetes or impaired fasting glucose, low high-density lipoprotein-cholesterol, and hypertriglyceridemia). Both the individual components of MetS and the cumulative number of MetS components were evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes were PCa detection overall, clinically significant PCa (CSPC; defined as any Gleason pattern ≥ 4, >50% involvement of a single biopsy core, or more than one of three total number of cores involved), and intermediate- or high-grade PCa (I-HGPC; Gleason 7-10). Tests for trend and multivariable logistic regression analyses were performed. RESULTS AND LIMITATIONS: Of 2235 patients, 494 (22.1%) had MetS. No individual MetS component was independently associated with PCa. However, increasing number of MetS components was associated with higher PCa grade (p<0.001), as well as progressively higher odds of PCa outcomes (three or more; ie, MetS) compared with no MetS components: Odds ratios were 1.54 for PCa overall (95% confidence interval [CI], 1.17-2.04; p=0.002), 1.56 for CSPC (95% CI, 1.17-2.08; p=0.002), and 1.56 for I-HGPC (95% CI, 1.16-2.10; p=0.003) in multivariable analyses. The main limitation is the retrospective design. CONCLUSIONS: Although the individual MetS components are not independently associated with PCa outcomes, MetS is significantly associated with higher odds of PCa diagnosis, CSPC, and I-HGPC. There is a biologic gradient between the number of MetS components and the risk of PCa, as well as cancer grade. PATIENT SUMMARY: Metabolic syndrome is a collection of metabolic abnormalities that increases one's risk for heart disease. Our study shows that an increasing degree of metabolic abnormality is also associated with an increased risk of diagnosis of overall and aggressive prostate cancer.

The impact of the use of aspirin and other nonsteroidal anti-inflammatory drugs on the risk of prostate cancer detection on biopsy.

OBJECTIVE: To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. METHODS: Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers. The primary outcome was any PC on biopsy, and the secondary outcome was clinically significant PC (CSPC; Gleason sum ≥7). Multivariate logistic regression analyses were performed to adjust for a priori defined clinical confounders. RESULTS: Of 839 patients, 408 (48.6%) were diagnosed with PC and 201 (24.0%) had CSPC. A higher proportion of ASA users (63.5%) and other NSAID users (61.2%) had PC compared with nonusers (41.9%; P <.001). CSPC was more common among ASA users (34.9%; P <.001) compared with other NSAID users (20.0%) and nonusers (20.9%). In multivariate regression analyses, ASA use (odds ratio [OR] = 2.04; 95% confidence interval [CI] = 1.32-3.13; P = .001) and other NSAID use (OR = 2.42; 95% CI = 1.36-431; P = .003) were associated with higher odds of PC detection, whereas ASA use was associated with higher odds of CSPC (OR = 1.62; 95% CI = 1.00-2.62; P = .048). CONCLUSION: In men undergoing biopsy, ASA and other NSAID use were associated with increased probability of detecting PC, whereas ASA use was associated with the risk of detecting CSPC. Although NSAID use might have a protective biological effect against PC, men who develop elevated prostate-specific antigen levels while on NSAIDs may nonetheless be less likely to have an inflammatory etiology and more likely to harbor PC. It may be warranted for clinicians to consider the influence of NSAIDs when evaluating patients being considered for biopsy.

Obesity is associated with larger prostate volume but not with worse urinary symptoms: analysis of a large multiethnic cohort.

OBJECTIVE: To evaluate the associations between body mass index (BMI) and prostate volume (PV) and lower urinary tract symptoms in a multiethnic cohort. METHODS: A cohort of men without prostate cancer seen at our institution was assembled, excluding those with previous transurethral resection of the prostate. Height and weight were measured to compute BMI, PV was measured by transrectal ultrasound, and the International Prostate Symptom Score (IPSS) questionnaire was administered. After stratified bivariate analyses, multiple linear regression and ordinal logistic regression models were used to assess the independent effect of BMI on PV and IPSS, respectively. RESULTS: The cohort included 1613 patients, and mean BMI was 27.1 kg/m(2). Patients with a BMI of <25.0, 25.0-29.9, and 30.0-34.9 had a median PV of 44.0 mL, 48.0 mL, and 52.0 mL, respectively. The African ethnicity subgroup generally had larger median PVs than European and Asian subgroups and had the largest differences in median PV between normal and obese men. There were no significant differences in IPSS or usage of benign prostatic hyperplasia medications between BMI categories. In multivariable analyses, higher BMI was associated with larger PV (P <.001) but not IPSS (P = .91). On the basis of our model, given a PV of 40 mL, 50 mL, and 60 mL, each 5 kg/m(2) increase in BMI was associated with a 2.19 mL, 2.74 mL, and 3.29 mL increase in PV, respectively. Body weight (P <.001) but not height (P = .13) was associated with PV. CONCLUSION: Higher BMI is associated with larger PV but not worse lower urinary tract symptoms (measured using IPSS). Usage rate of alpha blockers or 5 alpha reductase inhibitors was not significantly different between BMI categories.

Measurement of peri-prostatic fat thickness using transrectal ultrasonography (TRUS): a new risk factor for prostate cancer.

UNLABELLED: Study Type - Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? ADIPOSE tissue secretes various endocrine and paracrine mediators. Some authors have begun to consider whether peri-prostatic fat (PPF) may interact with the prostate and play a role in carcinogenesis. It has recently been shown that the PPF quantity measured by CT is associated with more aggressive disease in patients undergoing radiation therapy. Our group studied a population not yet diagnosed with prostate cancer. By doing so we were able to identify PPF thickness on transrectal ultrasonography as a risk factor for prostate cancer detection upon biopsy, and as a risk factor for high-grade disease. Our study also raises interesting questions about the underlying mechanisms of the association between PPF quantity and prostate cancer. OBJECTIVE: To determine if the amount of peri-prostatic fat (PPF) on transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer overall and high-grade prostate cancer (Gleason ≥4). PATIENTS AND METHODS: A prospectively maintained database of patients undergoing prostate biopsy at Princess Margaret Hospital for cancer suspicion was used. • All TRUS examinations were retrospectively reviewed upon 'blinding' to outcome. • PPF thickness, measured as the distance between the prostate and the pubic bone, was used as an index of the quantity of PPF. • PPF measurements, together with other prostate cancer risk factors, were evaluated against prostate cancer and high-grade prostate cancer detection upon biopsy with univariable and multivariable logistic regression and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Of the 931 patients, 434 (47%) were diagnosed with prostate cancer and 218 (23%) were diagnosed with high-grade prostate cancer. • The mean (range) PPF thickness was 5.3 (0-15) mm. • Increasing PPF thickness was associated with prostate cancer and high-grade prostate cancer diagnosis, with graded effect. When adjusting for other variables, the odds of detecting any prostate cancer and high-grade prostate cancer increased 12% (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23) and 20% (OR 1.20, 95% CI 1.07-1.34), respectively, for each millimetre increase in PPF thickness. • The AUCs for the association of PPF with prostate cancer and high-grade prostate cancer were 0.58 (95% CI 0.54-0.62) and 0.59 (95% CI 0.55-0.64), respectively. CONCLUSION: The amount of PPF can be estimated with TRUS and is a predictor of prostate cancer and high-grade prostate cancer at biopsy. To our knowledge, this study is the first to investigate PPF quantity in patients without prior prostate cancer diagnosis.