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Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) μmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) μmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) μmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) μmol/l ( - 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.

Objectives: To assess the utility of the percent free prostate-specific antigen (%fPSA) for the prediction of prostate cancer in men undergoing repeat biopsy., Methods: A retrospective review was performed of 1037 patients in an institutional review board-approved repeat prostate biopsy database. A total of 617 patients who underwent 683 biopsies had all their data available for analysis. The patients were categorized as having undergone 1 repeat biopsy or >1 repeat biopsy., Results: The overall cancer detection rate was 27% and 22% in men who underwent 1 and >1 repeat biopsy, respectively. The area under the receiver operating characteristic curve for the %fPSA was 0.65 for men who underwent 1 repeat biopsy. Multivariate analysis demonstrated that a positive family history, decreasing %fPSA, and presence of high-grade intraepithelial neoplasia and/or atypical small acinar proliferation predicted for cancer. The univariate odds ratio for every 5% decrease in the %fPSA was 1.5 (95% confidence interval 1.2-1.7). The performance of %fPSA was further improved in men who underwent >1 repeat biopsy, with an area under the curve of 0.72. In men who underwent >1 repeat biopsy, multivariate analysis showed that a decreasing %fPSA, >20 cores removed, and high-grade intraepithelial neoplasia predicted for cancer. The univariate odds ratio for every 5% decrease in the %fPSA was 1.8 (95% confidence interval 1.4-2.3). A %fPSA cutoff of 10% achieved 90% and 91% specificity in the 1 repeat biopsy and >1 repeat biopsy groups, respectively., Conclusions: %fPSA is useful in predicting for prostate cancer in the repeat biopsy population, particularly for those who have undergone multiple repeat biopsies. A persistently low %fPSA should prompt additional investigation in these men., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The Prostate Cancer Prevention Trial (PCPT) has challenged the validity of recommended prostate-specific antigen (PSA) thresholds for prostate biopsy (> 2.5 ng/ml) given the 17% prostate cancer (pCA) detection rate at PSA of 1.1-2.0. The outcome of patients treated at PSA < or = 2.5 is poorly defined, and advantages associated with such an early diagnosis are uncertain., Objective: Compare the outcome of patients with T1c pCA with pretreatment PSA < or = 2.5 and 2.6-4.0., Design, Setting, and Participants: Since 1998, 351 patients with clinical stage T1c and PSA < or = 4.0 have been treated at our institution; 84 (24%) of those patients had PSA < or = 2.5. Clinical information was obtained from a prospective database. Treatment was radical prostatectomy (RP), brachytherapy, and external-beam radiotherapy (EBRT) in 261 (74%), 67 (19%), and 23 (7%) patients, respectively., Intervention: Definitive therapy for clinically localized pCA., Measurements: Progression-free probability and pathologic end points., Results and Limitations: No significant differences between the groups were observed in terms of biopsy (18% vs 22%) or specimen Gleason score 7-8 (44% vs 56%), non-organ-confined cancer (11% vs 13%), indolent cancer (34% vs 24%), or 5-yr progression-free probability (89% vs 93%; p>0.1 for all). More biologically unimportant cancers (defined as pathologically organ-confined and Gleason < or = 6) were identified among patients with PSA < or = 2.5 (55% vs 41%, p=0.050), and indolent cancers were three times more frequent than non-organ-confined cancers among these patients (p=0.003)., Conclusions: The pathologic features and outcome of patients treated at low PSA levels are favorable and similar for patients with PSA < or = 2.5 versus 2.6-4.0. However, > 50% of the former have potentially biologically unimportant cancer. We failed to identify a therapeutic benefit to the diagnosis of cancers below accepted PSA thresholds for biopsy.

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.

The genetic transfer of antigen receptors is a powerful approach to rapidly generate tumor-specific T lymphocytes. Unlike the physiologic T-cell receptor, chimeric antigen receptors (CARs) encompass immunoglobulin variable regions or receptor ligands as their antigen recognition moiety, thus permitting T cells to recognize tumor antigens in the absence of human leukocyte antigen expression. CARs encompassing the CD3zeta chain as their activating domain induce T-cell proliferation in vitro, but limited survival. The requirements for genetically targeted T cells to function in vivo are less well understood. We have, therefore, established animal models to assess the therapeutic efficacy of human peripheral blood T lymphocytes targeted to prostate-specific membrane antigen (PSMA), an antigen expressed in prostate cancer cells and the neovasculature of various solid tumors. In vivo specificity and antitumor activity were assessed in mice bearing established prostate adenocarcinomas, using serum prostate-secreted antigen, magnetic resonance, computed tomography, and bioluminescence imaging to investigate the response to therapy. In three tumor models, orthotopic, s.c., and pulmonary, we show that PSMA-targeted T cells effectively eliminate prostate cancer. Tumor eradication was directly proportional to the in vivo effector-to-tumor cell ratio. Serial imaging further reveals that the T cells must survive for at least 1 week to induce durable remissions. The eradication of xenogeneic tumors in a murine environment shows that the adoptively transferred T cells do not absolutely require in vivo costimulation to function. These results thus provide a strong rationale for undertaking phase I clinical studies to assess PSMA-targeted T cells in patients with metastatic prostate cancer.

Prostate cancer has become a major public health issue and the search for etiologic risk factors and the development of chemopreventive agents has gained momentum over the last decade. An important epidemiologic finding has been the association between the consumption of tomato products and a lower risk of prostate cancer. Several investigators have proposed that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Laboratory and clinical studies have been initiated with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate cancer. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound may possibly reduce prostate cancer risk.