Biomedical subjects

Phyllis J Goodman

Publications and source records attributed to Phyllis J Goodman.

18 recordsLinked to original sources

PubMed2006

Effect of finasteride on the sensitivity of PSA for detecting prostate cancer.

BACKGROUND: In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer. We examined the impact of finasteride on the sensitivity and area under the receiver operating characteristic curve (AUC) of prostate-specific antigen (PSA) for detecting prostate cancer. METHODS: We studied men in the placebo and finasteride groups of the PCPT who had a prostate biopsy and concurrent PSA tests during the 7-year study. We compared the placebo and finasteride groups for sensitivity and AUC of PSA for the detection of all prostate cancer, of Gleason grade 7 or higher prostate cancer, and of Gleason grade 8 or higher prostate cancer. All statistical tests were two-sided. RESULTS: Of 5112 men in the placebo group, prostate cancer was detected in 1111. Gleason tumor grade was available for 1100 men, of whom 240 had grade 7 or higher and 55 had grade 8 or higher. Of 4579 men in the finasteride group, 695 had prostate cancer. Gleason grade was available for 686 men, of whom 264 had grade 7 or higher and 81 had grade 8 or higher. The AUC of PSA for all outcomes was greater for the finasteride group than the placebo group. For detecting prostate cancer versus no cancer, the AUCs were 0.757 and 0.681, respectively (P < .001); for detecting Gleason grade > or = 7 versus < or = 6 or no cancer, the AUCs were 0.838 and 0.781, respectively (P = .003); and for detecting Gleason grade > or = 8 versus < or = 7 or no cancer, the AUCs were 0.886 and 0.824, respectively (P = .071). The sensitivity of PSA was higher for men in the finasteride group than in the placebo group at all PSA cutoffs matched by specificity. CONCLUSIONS: PSA had statistically significantly better sensitivity and AUC for detecting prostate cancer in the finasteride arm of the PCPT than in the placebo arm. This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride.

Aged↗

PubMed2006

Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial.

BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who participated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. METHODS: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. RESULTS: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score > or =7) whereas a previous negative prostate biopsy reduced this risk. CONCLUSIONS: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy.

Black or African American↗

PubMed2006

Associations of demographic and lifestyle characteristics with prostate-specific antigen (PSA) concentration and rate of PSA increase.

BACKGROUND: The objective of this study was to examine whether demographic and lifestyle characteristics are associated with prostate-specific antigen (PSA) levels and the rate of PSA increase (PSA velocity). METHODS: Data for this study came from 3341 participants in the placebo arm of the Prostate Cancer Prevention Trial who, based on biopsies at the end of the study, were free of prostate carcinoma. Linear regression was used to assess associations of age, race, smoking, body mass index (BMI), physical activity, diet, and supplement use with PSA concentration during the second year of the trial, and linear mixed models were used to assess associations of these factors with PSA velocity (the percentage increase in PSA per year) during 6 years of the trial. RESULTS: Between the group of men ages 50-59 years and the group of men age 70 years and older, mean PSA increased by 0.22 ng/mL, and PSA velocity decreased by 1.2 percentage points (both P < 0.001). The PSA level among men who had a BMI > or = 35 kg/cm(2) was 0.20 ng/mL lower than the PSA level among men who had a BMI < 25 kd/cm(2) (P < 0.001), but BMI was not associated with PSA velocity. PSA velocity was 1.2 percentage points higher in African-American men compared with white men (P = 0.043). Low energy intake and the use of high-dose calcium supplements were associated with significantly lower PSA velocity (both P = 0.05). Weight gain also was associated with lower PSA velocity. CONCLUSIONS: Differences in PSA concentration associated with demographic and lifestyle characteristics were small and were not likely to bias the interpretation of a single PSA test. Age, race, energy intake, calcium supplement use, and weight change were associated with substantial differences in PSA velocity, and the clinical interpretation of PSA velocity may be biased by these factors.

Age Factors↗

PubMed2006

The prostate cancer prevention trial: design, biases and interpretation of study results.

PURPOSE: We describe the complexities of the study design of the PCPT and how they influenced the end point chosen, trial implementation, analysis and interpretation of the results. MATERIALS AND METHODS: Data from the PCPT are provided to evaluate and quantify the potential biases of this trial design. RESULTS: Six potential sources of bias, including prostate specific antigen, digital rectal examination, prostate biopsy technique, study medication nonadherence and contamination, and transurethral prostate resection are presented. These biases resulted in the need for the end of study biopsy to evaluate the trial objectives. CONCLUSIONS: There were a large number of known and potential biases that worked for and against finasteride. Because of the trial design and inherent biases, it is imperative that interim biopsy results should be interpreted with caution. While the period prevalence end point that relied on an end of study biopsy was perhaps not the most clinically relevant, it was the only way to remove as much bias as possible and meet the study objective of determining if finasteride could decrease the risk of prostate cancer. The success of the PCPT depended on constant scrutiny by the Data and Safety Monitoring Committee to monitor these biases. The design and biopsy assumptions outlined at the inception of the trial were met, including adherence and contamination rates, the for-cause biopsy rate and the final percent of men with study end points.

Bias↗

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↗

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

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

Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial.

PURPOSE: Studies have shown that finasteride decreases prostate specific antigen (PSA) by approximately 50% during the first 12 months of use. We estimated the long-term effects of finasteride on PSA in men with and without a prostate cancer diagnosis at the end of the study. MATERIALS AND METHODS: We analyzed serial PSA in participants in the Prostate Cancer Prevention Trial who had an end of study biopsy (928 with cancer and 8,620 with negative biopsy) or an interim diagnosis of prostate cancer (671). Linear mixed effects regression models were fit to longitudinal PSA values beginning 1 year after randomization. RESULTS: In subjects with no cancer in the end of study biopsy PSA in the finasteride arm showed a median annual decrease of 2% [corrected] after year 1, while PSA in the control arm showed an annual increase of 3% (p <0.001). In end of study cases PSA increased annually by 6% (placebo) and 7% (finasteride). In those with interim diagnoses PSA increased by 11% (placebo) and 15% (finasteride) each year prior to diagnosis. Cases with high grade disease (Gleason 7 and above) had greater PSA increases than cases with low grade disease (p <0.001). CONCLUSIONS: In men who have been receiving finasteride for more than 1 year time varying adjustment factors may be needed to determine whether PSA is in the normal range. In the Prostate Cancer Prevention Trial cohort the adjustment factor required to preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the initiation of finasteride.

Aged↗

PubMed2004

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

BACKGROUND: The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.

Aged↗

PubMed2004

Implementation of the Prostate Cancer Prevention Trial (PCPT).

The Prostate Cancer Prevention Trial is a randomized double blind chemoprevention trial of 18,882 men. It is designed to test the difference in the histologically proven prostate cancer prevalence between a group of participants given finasteride and another given placebo for 7 years. We present an overview of the study design, details of the administrative structure of the study and a description of the successful implementation of the accrual phase.

Chemoprevention↗

PubMed2004

Statistical design issues and other practical considerations for conducting phase III prostate cancer prevention trials.

PURPOSE: We briefly describe the purpose of phase II studies as a source of preliminary data for phase III prevention trials, and address statistical and other practical considerations for phase III prostate cancer prevention trials. MATERIALS AND METHODS: Objectives of 2 types of phase II studies and general criteria for validating surrogate end points are described, and statistical considerations needed for planning a phase III prevention trial are explained, including selection of an appropriate study population and end point, the corresponding expected event rate, estimates of loss to followup, and death and compliance rates. If a preventive agent has an impact on the ability to detect prostate cancer, additional study design considerations are then made. Other practical issues are addressed, including collection of biological materials for correlative studies, assessment of quality of life measures and the addition of ancillary studies that may include the collection of additional end points unrelated to prostate cancer. RESULTS: The Southwest Oncology Group is coordinating 2 recently reported phase III prostate cancer prevention trials. The Prostate Cancer Prevention Trial final results of 18,882 men randomized to either finasteride or placebo, and the Selenium and Vitamin E Cancer Prevention Trial has accrued more than half of its goal of 32,400 men. These studies are used to illustrate some statistical design features. CONCLUSIONS: The aforementioned trials provide valuable lessons in the successful design and conduct of phase III prostate cancer prevention trials.

Anticarcinogenic Agents↗

PubMed2003

The influence of finasteride on the development of prostate cancer.

BACKGROUND: Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS: Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS: Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

5-alpha Reductase Inhibitors↗

PubMed2003

The selenium and vitamin E cancer prevention trial.

BACKGROUND: Evidence suggests that both selenium and vitamin E reduce the risk of prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized, prospective, double-blind study designed to determine whether selenium and vitamin E alone and in combination can reduce the risk of prostate cancer among healthy men. MATERIALS AND METHODS: The preclinical and epidemiological evidence supporting a role for selenium and vitamin E as chemopreventive agents in prostate cancer are reviewed, and details of the trial design are presented. RESULTS. Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. SELECT is a 2x2 factorial study with an accrual goal of 32,400 men with nonsuspicious DRE and serum PSA of 4 ng/ml or lower. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013.

Clinical Trials as Topic↗

PubMed2002

Biomarker-based methods for determining noncompliance in a prevention trial.

The Prostate Cancer Prevention Trial (PCPT) is a 7-year randomized trial of 18000 men designed to test a daily dose of finasteride (5 mg/d) for the primary prevention of prostate cancer. Compliance is assessed every 6 months by determining the percentage of pills consumed since the previous visit. In addition, levels of 5 alpha-dihydrotestosterone (DHT) are measured at yearly intervals in a random subset of 5% of participants in the trial as part of a substudy to investigate the potential of this biomarker for monitoring compliance. Motivated by this substudy, we outline three biomarker-based rules for monitoring compliance over time in prevention trials. We make comparisons among the rules using receiver operating characteristic curves. We illustrate the methods using the biomarker DHT in the PCPT substudy with pill counts as a gold standard, and in a simulation study under a hypothetical true gold standard. Our results indicate that simple absolute threshold monitoring rules perform just as well as more complicated rules that utilize the entire biomarker history.

Aged↗

PubMedDate not supplied

SELECT: the selenium and vitamin E cancer prevention trial.

PURPOSE: Growing evidence suggests that both selenium and vitamin E may reduce the risk of prostate cancer. SELECT is a randomized, prospective, double-blind study designed to determine if selenium and vitamin E can reduce the risk of prostate cancer among healthy men. MATERIALS AND METHODS: The preclinical and epidemiologic evidence regarding chemoprevention with selenium and vitamin E were reviewed. Secondary analyses from randomized trials of both agents were included in the analysis. Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the schema of SELECT. RESULTS: Preclinical, epidemiologic, and Phase III data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial and the rapid accrual of SELECT during its first year demonstrate the interest and dedication of healthy men to long-term studies of cancer prevention. A total of 32,400 men are planned to be randomized in SELECT. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013.

Adenocarcinoma↗