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Ian M Thompson

Publications and source records attributed to Ian M Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2006

Obesity, adipokines, and prostate cancer in a prospective population-based study.

BACKGROUND: The purpose of this investigation was to examine the association of obesity and the adipokines leptin, adiponectin, and interleukin-6 (IL-6) with prostate cancer risk and aggressiveness. METHODS: One hundred twenty-five incident prostate cancer cases and 125 age-matched controls were sampled from among participants in the original San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. The odds ratios (OR) of prostate cancer and high-grade disease (Gleason sum >7) associated with the WHO categories of body mass index (kg/m(2)) and with tertiles of serum concentrations of adiponectin, leptin, and IL-6 were estimated using multivariable conditional logistic regression models. RESULTS: Body mass index was not associated with either incident prostate cancer [obese versus normal; OR, 0.75; 95% confidence interval (95% CI), 0.38-1.48; P(trend) = 0.27] or high-grade versus low-grade disease (OR, 1.17; 95% CI, 0.39-3.52; P(trend) = 0.62). Moreover, none of the three adipokines was statistically significant associated with prostate cancer risk or high-grade disease, respectively: leptin (highest versus lowest tertile; OR, 0.77; 95% CI, 0.28-1.37; P(trend) = 0.57; OR, 1.20; 95% CI, 0.48-3.01; P(trend) = 0.85); adiponectin (OR, 0.87; 95% CI, 0.46-1.65; P(trend) = 0.24; OR, 1.93; 95% CI, 0.74-5.10; P(trend) = 0.85); IL-6 (OR, 0.84; 95% CI, 0.46-1.53; P(trend) = 0.98; OR, 0.84; 95% CI, 0.30-2.33; P(trend) = 0.17). CONCLUSIONS: Findings from this nested case-control study of men routinely screened for prostate cancer and who had a high prevalence of overweight and obesity do not provide evidence to support that prediagnostic obesity or factors elaborated by fat cells strongly influence prostate cancer risk or aggressiveness. However, due to the small sample population, a small or modest effect of obesity and adipokines on these outcomes cannot be excluded.

Adiponectin↗
PubMed2006

Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial.

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes.

Adenocarcinoma↗
PubMed2006

Chemoprevention of prostate cancer with finasteride.

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5alpha-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5alpha-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

Animals↗
PubMed2005

Erectile dysfunction and subsequent cardiovascular disease.

CONTEXT: The risk factors for cardiovascular disease and erectile dysfunction are similar. OBJECTIVE: To examine the association of erectile dysfunction and subsequent cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Men aged 55 years or older who were randomized to the placebo group (n = 9457) in the Prostate Cancer Prevention Trial at 221 US centers were evaluated every 3 months for cardiovascular disease and erectile dysfunction between 1994 and 2003. Proportional hazards regression models were used to evaluate the association of erectile dysfunction and cardiovascular disease. In an adjusted model, covariates included age, body mass index, blood pressure, serum lipids, diabetes, family history of myocardial infarction, race, smoking history, physical activity, and quality of life. MAIN OUTCOME MEASURES: Erectile dysfunction and cardiovascular disease. RESULTS: Of the 9457 men randomized to placebo, 8063 (85%) had no cardiovascular disease at study entry; of these men, 3816 (47%) had erectile dysfunction at study entry. Among the 4247 men without erectile dysfunction at study entry, 2420 men (57%) reported incident erectile dysfunction after 5 years. After adjustment, incident erectile dysfunction was associated with a hazard ratio of 1.25 (95% confidence interval [CI], 1.02-1.53; P = .04) for subsequent cardiovascular events during study follow-up. For men with either incident or prevalent erectile dysfunction, the hazard ratio was 1.45 (95% CI, 1.25-1.69; P<.001). For subsequent cardiovascular events, the unadjusted risk of an incident cardiovascular event was 0.015 per person-year among men without erectile dysfunction at study entry and was 0.024 per person-year for men with erectile dysfunction at study entry. This association was in the range of risk associated with current smoking or a family history of myocardial infarction. CONCLUSIONS: Erectile dysfunction is a harbinger of cardiovascular clinical events in some men. Erectile dysfunction should prompt investigation and intervention for cardiovascular risk factors.

Aged↗
PubMed2005

Phase III prostate cancer prevention trials: are the costs justified?

One randomized, prospective clinical trial for chemoprevention of prostate cancer has been completed, and two additional trials are ongoing. The investment, time, and effort for these trials are substantial. We reviewed the outcomes of these trials to address the value of the investment. The outcomes of the Prostate Cancer Prevention Trial (testing finasteride) and the design of the Selenium and Vitamin E Cancer Prevention Trial (SELECT; testing vitamin E and selenium) trial as well as the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (testing dutasteride) were reviewed. From a public health standpoint, there is tremendous potential for benefit from large-scale cancer prevention trials. Because of the volume of data that are collected, potential discoveries related to the biology of the disease are substantial. Translational scientific efforts are direct outgrowths of these studies. Prospective, randomized chemoprevention trials for prostate and other cancers are expensive and require long periods of time to conduct, yet the rewards are on a par with the investment.

Clinical Trials, Phase III as Topic↗
PubMed2005

Assessing benefit and risk in the prevention of prostate cancer: the prostate cancer prevention trial revisited.

PURPOSE: The Prostate Cancer Prevention Trial demonstrated a 25% reduction in period prevalence of prostate cancer in men randomly assigned to 5 mg/d of finasteride. However, widespread use of finasteride for prevention is inhibited by the observed increased risk of high-grade disease. We present a model of risk and benefit that estimates the potential effects of histologic artifact in the assignment of excess risk for high-grade disease and the possible effect of overdetection bias introduced by finasteride-induced volume reduction. METHODS: The absolute benefit/absolute risk ratio of finasteride use was estimated by calculating the ratio of absolute risk reduction in the finasteride arm to the absolute risk of excess high-grade cancers. This ratio was recalculated for assumptions that 10%, 25%, or 50% of the excess high-grade cancers were due to histologic artifact, and that there was a 25% overdetection bias in the finasteride arm. RESULTS: For all cancers the absolute benefit/absolute risk ratio increased from 4.6:1 to 5.1:1, 6.2:1, and 9.2:1 for assumptions of 10%, 25%, or 50% histologic artifact, respectively. The ratio increased from 4.6:1 to 8.2:1 for the assumption of 25% overdetection bias, and to 9.1:1, 10.9:1, and 16.3:1 for combined assumptions of 25% overdetection bias and 10%, 25%, or 50% histologic artifact, respectively. CONCLUSION: The adoption of a prevention strategy hinges on potential benefits weighed against potential risks. This model demonstrates the magnitude of effect for a hypothesized range of histologic artifact and overdetection bias on the assessment of risk versus benefit for finasteride.

Adenocarcinoma↗
PubMed2005

Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower.

CONTEXT: Three fourths of US men older than 50 years have been screened with prostate-specific antigen (PSA) for prostate cancer. OBJECTIVE: To estimate the receiver operating characteristic (ROC) curve for PSA. DESIGN, SETTING, AND PARTICIPANTS: Calculation of PSA ROC curves in the placebo group of the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men. MAIN OUTCOME MEASURES: Operating characteristics of PSA for prostate cancer detection, including sensitivity, specificity, and ROC curve. RESULTS: Of 8575 men in the placebo group with at least 1 PSA measurement and digital rectal examination in the same year, 5587 (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95% confidence interval [CI], 0.666-0.689), 0.782 (95% CI, 0.748-0.816), and 0.827 (95% CI, 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed slightly better performance of PSA in men younger than 70 years vs those 70 years or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P = .03). CONCLUSION: There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA.

Aged↗
PubMed2005

Estimated impact of the Prostate Cancer Prevention Trial on population mortality.

BACKGROUND: The potential public health impact of the recently completed Prostate Cancer Prevention Trial (PCPT) is debated. The results indicated that the period prevalence of prostate cancer was reduced by 24.8% due to finasteride, whereas an increase in the rate of high-grade tumors (Gleason score 8-10) among men who were diagnosed with cancer also was found (5.0% in the PCPT placebo arm vs. 11.9% in the PCPT finasteride arm). Whether the increased Gleason score was valid or was a histologic artifact is under investigation. METHODS: The authors estimated the number of person-years saved assuming a 24.8% reduction in the incidence of prostate cancer for 5 years among United States males age > or = 55 years. Scenarios for different proportions of patients with high-grade Gleason scores also were considered. RESULTS: With a 24.8% reduction in the number of men with newly diagnosed prostate cancer, the authors estimated that 316,760 person-years would be saved due to finasteride in the United States. An absolute increase of 6.9% in the proportion of men with high-grade tumors in the United States cancer population (corresponding to the difference between the rates on the placebo and finasteride arms of the PCPT) would reduce the number of person-years saved to 262,567. For each absolute increase of 5% in the proportion of patients with high-grade tumors, the number of person-years saved would be reduced by approximately 39,000. CONCLUSIONS: The results of the PCPT may have a major impact on population mortality from prostate cancer if they are applied clinically. The potential detrimental effects of an increased rate of patients who have prostate cancer with high-grade Gleason scores would be outweighed by a reduction in incidence.

Finasteride↗
PubMed2005

Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Prostate cancer continues to be a major health threat, especially among African American men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which opened on July 25, 2001, was planned to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States, including Puerto Rico, and Canada. SELECT is a phase III randomized, placebo-controlled trial of selenium (200 microg/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years) in non-African American men at least 55 years of age and African American men at least 50 years of age. SELECT is a large, simple trial that conforms as closely as possible with community standards of care. This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial, including the role of prostate cancer screening, the best forms and doses of the study agents, and estimation of the event (prostate cancer) rate of men on the placebo arm.

Black or African American↗
PubMed2005

Prevention of hormone-related cancers: prostate cancer.

Androgens are known to play an important role in normal prostate development, benign prostatic hyperplasia, established prostate cancer, and in prostate carcinogenesis. However, despite convincing experimental and clinical evidence, the epidemiologic data correlating sex steroid levels with disease risk is inconsistent. More recent work has focused on studies of polymorphisms in germ-line DNA in an effort to develop polygenic models of prostate cancer susceptibility and prognosis. Such models have the potential to aid in the selection of men for specific chemopreventive interventions and to help determine which men with localized prostate cancer are most likely to benefit from aggressive therapy. In this review, we will provide a brief summary of androgen metabolic pathways followed by an assessment of the epidemiology literature addressing the relationship between androgens and prostate cancer. Finally, we will address the two major questions that have arisen in response to the recently published results from the Prostate Cancer Prevention Trial: Who are the best candidates for finasteride chemoprevention, and what are the clinical implications of the high prevalence of prostate cancer that was detected in men with prostate-specific antigen levels in the so-called "normal" range?

Androgens↗
PubMed2005

Biomarkers for the detection and prognosis of prostate cancer.

Recent studies have cast doubt on the reliability of serum total prostate-specific antigen as a biomarker for the detection and prognosis of prostate cancer. Biomarkers that can identify those men at risk for clinically significant prostate cancer are desperately needed. The search for biomarkers that may improve the detection of biologically consequential prostate cancer is one of the most active areas under current investigation. In this review, we highlight some of these ongoing efforts. Proper validation of newly discovered biomarkers is of paramount importance.

Biomarkers, Tumor↗
PubMed2005

What's new in the field of prostate cancer chemoprevention?

Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.

Antineoplastic Agents↗
PubMed2005

Local and systemic therapy for patients with metastatic prostate cancer: should the primary tumor be treated?

Data from well-designed, prospective clinical trials are lacking to support treatment of primary tumor in men diagnosed with metastatic prostate cancer. However, a growing body of evidence suggests that treatment of the primary tumor may enhance cancer control and survival in some men. This evidence is examined and recommendations are made for identifying patients with metastatic prostate cancer who may benefit from definitive treatment of the prostate tumor.

Androgen Antagonists↗