Context Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Design, Setting, and Participants Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Interventions Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Results Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7.33). Hazard ratios (number of prostate cancers, 99% confidence intervals [CIs]) for prostate cancer were 1.13 for vitamin E (n=473; CI, 0.91–1.41), 1.04 for selenium (n=432; CI, 0.83–1.30), and 1.05 for the combination (n=437; CI, 0.83–1.31) compared with placebo (n=416). There were no significant differences (all p-values > 0.15) in any prespecified cancer endpoints. There were nonsignificant increased risks of prostate cancer in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0l95–1.35) and of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22), but they were not observed in the combination arm. Conclusion Selenium or vitamin E, alone or in combination, did not prevent prostate cancer in this population at the doses and formulations used.

Context The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a non-statistically significant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. Objective To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. Design, Setting and Participants SELECT randomized 35,533 men from 427 study sites in the United States, Canada and Puerto Rico in a double-blind manner between August 22, 2001 and June 24, 2004. Eligible men were 50 years or older (African Americans) or 55 years or older (all others) with a PSA ≤4.0 ng/mL and a digital rectal examination not suspicious for prostate cancer. Included in the analysis are 34,887 men randomly assigned to one of four treatment groups: selenium (n=8752), vitamin E (n=8737), both agents (n=8702), or placebo (n=8696). Data reflect the final data collected by the study sites on their participants through July 5, 2011. Interventions Oral selenium (200 μg/day from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer incidence. Results This report includes 54,464 additional person-years of follow-up since the primary report. Hazard ratios (99% confidence intervals [CI]) and numbers of prostate cancers were 1.17(99% CI 1.004-1.36, p=.008, n=620) for vitamin E, 1.09 (99% CI 0.93-1.27, p=.18, n=575) for selenium, 1.05 (99%CI 0.89-1.22, p=.46, n=555) for selenium + vitamin E vs. 1.00 (n=529) for placebo.The absolute increase in risk compared with placebo for vitamin E, selenium and the combination were 1.6, 0.9 and 0.4 cases of prostate cancer per 1,000 person-years. Conclusions Dietary supplementation with Vitamin E significantly increases the risk of prostate cancer among healthy men. Trial registration clinicaltrials.gov identifier: NCT00006392

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Diffusion weighted imaging (DWI) has been at the forefront of cancer imaging since the early 2000’s. Prior to its application in clinical oncology, this powerful technique had already achieved widespread recognition due to its utility in the diagnosis of cerebral infarction. Following this initial success, the ability of DWI to detect inherent tissue contrast began to be exploited in the field of oncology. Although the initial oncologic applications for tumor detection and characterization, assessing treatment response, and predicting survival were primarily in the field of neuro-oncology, the scope of DWI has since broadened to include oncologic imaging of the prostate gland, breast, and liver. Despite its growing success and application, misconceptions as to the underlying physical basis of the DWI signal exist among researchers and clinicians alike. In this review, we provide a detailed explanation of the biophysical basis of diffusion contrast, emphasizing the difference between hindered and restricted diffusion, and elucidating how diffusion parameters in tissue are derived from the measurements via the diffusion model. We describe one advanced DWI modeling technique, called Restriction Spectrum Imaging (RSI). This technique offers a more direct in vivo measure of tumor cells, due to its ability to distinguish separable pools of water within tissue based on their intrinsic diffusion characteristics. Using RSI as an example, we then highlight the ability of advanced DWI techniques to address key clinical challenges in neuro-oncology, including improved tumor conspicuity, distinguishing actual response to therapy from pseudoresponse, and delineation of white matter tracts in regions of peritumoral edema. We also discuss how RSI, combined with new methods for correction of spatial distortions inherent diffusion MRI scans, may enable more precise spatial targeting of lesions, with implications for radiation oncology, and surgical planning.

Context-The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a non-statistically significant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.Objective-To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.Design, Setting and Participants-SELECT randomized 35,533 men from 427 study sites in the United States, Canada and Puerto Rico in a double-blind manner between August 22, 2001 and June 24, 2004. Eligible men were 50 years or older (African Americans) or 55 years or older (all others) with a PSA ≤4.0 ng/mL and a digital rectal examination not suspicious for prostate cancer. Included in the analysis are 34,887 men randomly assigned to one of four treatment groups: selenium (n=8752), vitamin E (n=8737), both agents (n=8702), or placebo (n=8696). Data reflect the final data collected by the study sites on their participants through July 5, 2011.Interventions-Oral selenium (200 μg/day from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. Main Outcome Measures-Prostate cancer incidence.Results-This report includes 54,464 additional person-years of follow-up since the primary report. Hazard ratios (99% confidence intervals [CI]) and numbers of prostate cancers were 1.17(99% CI 1.004-1.36, p=.008, n=620) for vitamin E, 1.09 (99% CI 0.93-1.27, p=.18, n=575) for selenium, 1.05 (99%CI 0.89-1.22, p=.46, n=555) for selenium + vitamin E vs. 1.00 (n=529) for placebo.The absolute increase in risk compared with placebo for vitamin E, selenium and the combination were 1.6, 0.9 and 0.4 cases of prostate cancer per 1,000 person-years.Conclusions-Dietary supplementation with Vitamin E significantly increases the risk of prostate cancer among healthy men. Trial registration-clinicaltrials.gov identifier: NCT00006392Lifetime risk of prostate cancer in the United Sates is currently estimated to be 16%. 1 While most cases are found at an early, curable stage, treatment is costly and urinary, sexual, and bowel-related side effects are common. 2 Even men who choose active surveillance as an initial management strategy face anxiety, uncertain prognosis, and a measurable risk of sepsis with follow-up biopsies 3 , and more than one-third of those who initially defer therapy are ultimately treated. 4,5 With such a high prevalence, risk of morbidity from treatment, and treatment-related costs, primary prevention of prostate cancer is an attractive option.With considerable preclinical and epidemiologic evidence that selenium and vitamin E may reduce prostate cancer risk, we conducted and reported the results of a prospective were not st...