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Background: Previously, we showed that carbohydrate restriction with calorie restriction slowed tumor growth in xenograft mouse prostate cancer models. Herein, we examined the impact of carbohydrate restriction without calorie restriction on tumor development within the context of diet-induced obesity in the Hi-Myc transgenic mouse model of prostate cancer., Methods: Mice were randomized at 5 weeks of age to ad libitum western diet (WD; 40% fat, 42% carbohydrate; n=39) or ad libitum no carbohydrate ketogenic diet (NCKD; 82% fat, 1% carbohydrate; n=44). At age 3 or 6 months, mice were killed, prostates weighed and prostate histology, proliferation, apoptosis and macrophage infiltration evaluated by hematoxylin and eosin, Ki67, TUNEL and F4/80 staining, respectively. Body composition was assessed by DEXA, serum cytokines measured using multiplex, and Akt/mTOR signaling assessed by Western., Results: Caloric intake was higher in the NCKD group, resulting in elevated body weights at 6 months of age, relative to the WD group (45 g vs 38g; P=0.008). Despite elevated body weights, serum monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-1α levels were lower in NCKD versus WD mice (P=0.046 and P=0.118, respectively), and macrophage infiltration was reduced in prostates of NCKD versus WD mice (P=0.028). Relative Akt phosphorylation and phospho-S6 ribosomal protein levels were reduced in prostates of NCKD versus WD mice. However, while mice randomized to NCKD had smaller prostates after adjustment for body weight at 3 and 6 months (P=0.004 and P=0.002, respectively), NCKD mice had higher rates of adenocarcinoma at 6 months compared to WD mice (100 vs 80%, P=0.04)., Conclusions: Despite higher caloric intake and elevated body weights, carbohydrate restriction lowered serum MCP-1 levels, reduced prostate macrophage infiltration, reduced prostate weight, but failed to slow adenocarcinoma development. Together, these data suggest that although carbohydrate restriction within the context of obesity may reduce obesity-associated systemic inflammation and perhaps slow tumor growth, it is not sufficient to counteract obesity-associated tumor development.

Background: At the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment., Methods: We conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m 2 , overweight 25-29.9 kg/m 2 and obese ⩾30 kg/m 2 ). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk., Results: On crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant., Conclusions: Overweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM., Competing Interests: All authors declared no conflicts of interest Conflict of Interest: None

The American Cancer Society's updated screening guidelines for prostate cancer (CaP) render digital rectal examination (DRE) optional. We investigated the impact of DRE on CaP detection among obese men. Data from 2794 men undergoing initial prostate biopsy at three centers were analyzed to assess CaP risk attributed to abnormal DRE across body mass index (BMI) categories. Predictive accuracies of a combination of PSA, age, race, center and biopsy year including or excluding DRE findings were compared by areas under the receiver-operating characteristics curves. In all cohorts, obese men were less likely to have abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal DREs became stronger predictors for overall CaP in individual (P-trends ≤ 0.05) and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P-trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the predictive accuracy for overall and high-grade CaP detection among all obese men (P ≤ 0.032) but not normal-weight men (P ≥ 0.198). DRE inclusion also near-significantly improved overall CaP detection in obese men with PSA<4 ng ml(-1) (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and is significantly higher among obese men than normal-weight men.

Background: The study aims to investigate the relationship between obesity and prostate cancer diagnosis at biopsy., Methods: From 2005 onwards, a consecutive series of patients undergoing 12-core prostate biopsy for PSA value ≥ 4 ng/ml and/or positive digital rectal examination (DRE) were enrolled. Before the biopsy, patients underwent a physical examination, including height and weight measurement. Obesity was defined as body mass index (BMI) ≥30 kg/m(2). Blood samples were drawn from all patients and analyzed for total PSA and testosterone., Results: 885 patients were enrolled with a median age and PSA of 67 years (range 37-95) and 6.4 ng/ml (range 1-30) respectively. Median BMI was 27.1 kg/m(2) (range 18-46.6) with 185 patients classified as obese. 363 patients had cancer at biopsy; 76 were obese. PSA was independently associated with a higher risk of cancer (OR 1.09 per 1 unit PSA, p = 0.01). On multivariate analysis, the BMI was not significantly associated with an increased prostate cancer risk (p = 0.19). Out of 363 patients with prostate cancer, 154 had a Gleason score 6 (23 were obese) and 209 a Gleason score ≥7 (53 were obese). Among men with cancer, a higher BMI on univariate (p = 0.001) and multivariate analysis (p = 0.005) was associated with high-grade disease (Gleason ≥ 7)., Conclusions: In our single center study and less aggressively screened cohort, obesity is associated with an increased risk of a high-grade Gleason score when prostate cancer is diagnosed at biopsy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and high-grade disease (Gleason >or=4+3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m(-2), respectively. Increased BMI was significantly associated with younger age (P<0.001), black race (P<0.001), more recent year of surgery (P<0.001), and positive surgical margins (P<0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P=0.003), increased tumor volume (P<0.001), and high-grade disease (P=0.007). Men with a BMI >or=35 kg m(2) had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers.