Biomedical subjects

John K Gohagan

Publications and source records attributed to John K Gohagan.

13 recordsLinked to original sources

PubMed2007

Repeat prostate biopsy in the prostate, lung, colorectal and ovarian cancer screening trial.

OBJECTIVE: To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS AND METHODS: The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate-specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow-up of positive screening results is done by the subject's healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings. RESULTS: The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA-positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing. CONCLUSION: The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy.

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PubMed2006

Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial.

OBJECTIVES: Prostate volume correlates both with prostate-specific antigen (PSA) values and with the presence of benign prostatic hyperplasia (BPH). Here we examine the relationship between prostate volume and PSA level in a large, geographically diverse sample of men undergoing prostate cancer screening. METHODS: We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated by DRE performed by trained examiners at the PLCO sites. Linear and logistic regression was used to assess the effect of prostate volume and age on PSA levels. Regression coefficients were adjusted for the effect of prostate volume measurement error. RESULTS: Prostate volume estimated by DRE showed considerable measurement error. Averaging volume over screening visits and accounting for examiner bias greatly reduced this error. Linear regression analysis showed a slope of 0.030/cm3 of log PSA on prostate volume when correcting for measurement error (95% confidence interval [CI], 0.029 to 0.031). Age was independently associated with (log) PSA, with a slope of 0.022 per year. Logistic regression analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm3 increase in prostate volume. The correlation of log PSA and prostate volume was 0.37. Prostate volume was not correlated with body mass index and showed weak correlation (r = 0.14) with age. CONCLUSIONS: Prostate volume and age are independently associated with increased PSA levels in a population of men undergoing screening.

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PubMed2006

Prostate specific antigen changes as related to the initial prostate specific antigen: data from the prostate, lung, colorectal and ovarian cancer screening trial.

PURPOSE: Annual screening with PSA, although of unproven benefit, is currently used for prostate cancer early detection. A large fraction of screened men have low (less than 2 ng/ml) initial PSA. The yield over time of positive PSA screens (ie more than 4 ng/ml) in these men has not been well characterized in large cohorts in the United States. MATERIALS AND METHODS: Men in the screening arm of the PLCO received baseline PSA and annual tests for 5 years. 30,495 of these men had baseline PSA 4 ng/ml or less. We estimated the cumulative probability of converting to PSA greater than 4 at years 1 through 5 as a function of baseline PSA. RESULTS: Among men with baseline PSA less than 1 ng/ml, 1.5% converted by year 5 (95% CI 1.2-1.7). Among men with baseline PSA of 1.0 to 1.99 ng/ml, 1.2% (95% CI 0.9-1.3) and 7.4% (95% CI 6.8-8.1) converted by year 1 and 5, respectively. A total of 33.5% and 79% of men with initial PSA of 2.0 to 2.99 and 3.0 to 4.0, respectively, converted by year 5. Of men with baseline PSA less than 1 ng/ml converting to PSA more than 4 ng/ml, 8% were diagnosed with cancer within 2 years of conversion. About 10% of men with baseline PSA less than 1 ng/ml and negative baseline DRE had a positive DRE within 3 years. CONCLUSIONS: For men choosing PSA screening, screening every 5 years for baseline PSA less than 1 ng/ml and every 2 years for PSA 1 to 2 ng/ml could result in a 50% reduction in PSA tests and in less than 1.5% of men missing earlier positive screens, but with an unknown effect on prostate cancer mortality.

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PubMed2005

Baseline chest radiograph for lung cancer detection in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

BACKGROUND: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round. METHODS: Of the 154,942 participants enrolled, who were aged 55-74 years with no history of PLCO cancers, 77,465 were randomly assigned to the intervention arm. Current or former smokers and never smokers in this arm received an initial single-view posterior-anterior chest radiograph. RESULTS: In the initial screen, 5991 (8.9%, 95% confidence interval [CI] = 8.7% to 9.2%) of radiographs were suspicious for lung cancer: 8.2% (95% CI = 7.9% to 8.5%) for women and 9.6% (95% CI = 9.3% to 10.0%) for men. Rates were highest for older age groups and for smokers. Among those 5991 participants with a positive screen, 206 (3.4%, 95% CI = 3.0% to 3.9%) underwent biopsy examination, 126 (61.2%, 95% CI = 54.5% to 67.8%) of whom were diagnosed with lung cancer within 12 months of the screen (59 in women and 67 in men). The positive predictive value was 2.1% (95% CI = 1.7% to 2.5%), and 1.9 lung cancers were detected per 1000 screens. Among these cancers, 44% (95% CI = 35% to 52%) were stage I non-small-cell lung cancer. High rates of lung cancer were found in current smokers (6.3 per 1000 screens) and in former smokers who had smoked within the past 15 years (4.9 per 1000 screens). The lung cancer detection rate among never smokers was 0.4 per 1000 screens; this group accounted for 11% (95% CI = 5.6% to 16.6%) of the cancers identified. CONCLUSIONS: In the baseline screen, nearly half the cancers were stage I. Whether this experience results in a reduction in lung cancer mortality is yet to be seen.

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PubMed2005

Flexible sigmoidoscopy in the PLCO cancer screening trial: results from the baseline screening examination of a randomized trial.

BACKGROUND: The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial is a randomized clinical trial to test the effectiveness of cancer screening, including the effect of flexible sigmoidoscopy screening on colorectal cancer mortality. Here we report findings from the baseline screening flexible sigmoidoscopy examination. METHODS: Analyses included 77,465 men and women aged 55-74 years who were enrolled at 10 screening centers. The trial administered baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy examinations, referred patients with screen-detected colorectal polyps or masses to personal physicians, and tracked subjects with polyps or masses to determine results from diagnostic follow-up. Cochran-Mantel-Haenszel statistics and logistic regression were used to test for differences in proportions according to sex and age. RESULTS: A total of 64 658 subjects (83.5%) underwent screening flexible sigmoidoscopy, and at least one polyp or mass was identified in 15,150 subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures. Follow-up lower endoscopy was more frequent in subjects with at least one larger (> or = 0.5 cm) polyp or mass (86.0% [95% confidence interval {CI} = 84.6% to 87.4%] and 81.0% [95% CI = 79.8% to 82.2%] in women and men, respectively) than in those with a smaller (< 0.5 cm) polyp or mass (69.1% [95% CI = 67.5% to 70.6%] and 65.4% [95% CI = 64.1% to 66.7%] in women and men, respectively). The yields per 1000 screened, depending on 5-year age group, were as follows: for colorectal cancer, 1.1-2.5 in women and 2.4-5.6 in men; for advanced adenoma, 18.0-30.4 in women and 36.1-49.1 in men; and for colorectal cancer or any adenoma, 50.6-79.6 in women and 101.9-128.6 in men. Approximately 77% (130/169) of the colorectal adenocarcinoma patients were stage I or II at diagnosis. CONCLUSIONS: Acceptance of screening flexible sigmoidoscopy was high. Diagnostic follow-up varied according to polyp size, yet cancer or adenoma detection rates met expectations.

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PubMed2005

Prostate Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of a randomized trial.

BACKGROUND: The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. METHODS: A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. RESULTS: Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. CONCLUSION: The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.

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PubMed2005

Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial.

OBJECTIVE: Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial. STUDY DESIGN: This was a randomized controlled trial of screening versus usual care. Baseline screening results are reported. RESULTS: Of 39,115 women randomized to receive screening, 28,816 received at least 1 test. Abnormal TVU was found in 1338 (4.7%), and abnormal CA-125 in 402 (1.4%). Twenty-nine neoplasms were identified (26 ovarian, 2 fallopian, and 1 primary peritoneal neoplasm). Nine were tumors of low malignant potential and 20 were invasive. The positive predictive value for invasive cancer was 3.7% for an abnormal CA-125, 1.0% for an abnormal TVU, and 23.5% if both tests were abnormal. CONCLUSION: The effect of screening on ovarian cancer mortality in the PLCO cohort has yet to be evaluated and will require longer follow-up. Screening identified both early- and late-stage neoplasms, and the predictive value of both tests was relatively low.

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PubMed2005

Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.

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PubMed2005

Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial.

PURPOSE: The benefit of prostate specific antigen (PSA) and digital rectal examination (DRE) screening for prostate cancer is under evaluation in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Followup of positive screens in PLCO is done by subject personal physicians and it is outside of trial control. We describe the pattern of prostate biopsy in men with positive screens in PLCO. MATERIALS AND METHODS: We examined all men with positive baseline PSA or DRE screens and men with positive post-baseline screens occurring by December 2000. RESULTS: Of 2,717 men with positive PSA (greater than 4 ng/ml) at baseline 41% and 64% underwent biopsy within 1 and 3 years, respectively. A screening PSA of 7 to 10 and greater than 10 ng/ml at baseline was associated with significantly higher biopsy rates (HR 1.9 and 2.6, respectively) compared to PSA 4 to 7 ng/ml. The 1,793 in men whom the first positive PSA was after baseline had a lower overall biopsy rate (50% within 3 years). Furthermore, PSA above 7 ng/ml were not associated with higher biopsy rates in this group. The 4,449 men with positive DRE screens and negative PSA had a 3-year biopsy rate of 27%. Men with positive DRE at diagnostic followup had a biopsy rate of around 90%. However, few men, even of those with positive DRE screens, had positive diagnostic DREs. CONCLUSIONS: : These biopsy rates following positive PSA and DRE screens are likely to be representative of national rates. These results suggest that PLCO is evaluating the effects of screening in a contemporary and robust manner.

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PubMed2003

Results of repeat sigmoidoscopy 3 years after a negative examination.

CONTEXT: The necessary frequency of endoscopic colorectal cancer screening after a negative examination is uncertain. OBJECTIVE: To examine the yield of adenomas and cancer in the distal colon found by repeat flexible sigmoidoscopy (FSG) 3 years after a negative examination. DESIGN, SETTING, AND PARTICIPANTS: Participants were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a randomized, controlled community-based study of cancer screening. The mean (SD) age was 65.7 (4.0) years at study entry (1993-1995) and 61.6% were men. Individuals underwent screening FSG at baseline and at 3 years as part of the protocol and were referred to their personal physicians for further evaluation of screen-detected abnormalities. Results from subsequent diagnostic evaluations were tracked in a standardized fashion. Of 11 583 eligible for repeat screening FSG 3 years after an initial negative examination, 9317 (80.4%) returned. MAIN OUTCOME MEASURES: Polyp or mass detection in distal colon at year 3 repeat FSG; incidence of adenoma or cancer in distal colon at year 3 examination; determination of reason for detection (increased depth of insertion or improved preparation at the year 3 examination or detection in a previously examined area). RESULTS: A total of 1292 returning participants (13.9%) had a polyp or mass detected by FSG 3 years after the initial examination. In the distal colon, 3.1% (292/9317) were found to have an adenoma or cancer. The incidence of advanced adenoma (n = 72) or cancer (n = 6) in the distal colon was 78 (0.8%) of 9317. Of individuals with advanced distal adenomas detected at the year 3 examination, 80.6% (58/72) had lesions found in a portion of the colon that had been adequately examined at the initial sigmoidoscopy. CONCLUSIONS: Repeat FSG 3 years after a negative examination will detect advanced adenomas and distal colon cancer. Although the overall percentage with detected abnormalities is modest, these data raise concern about the impact of a prolonged screening interval after a negative examination.

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PubMed2003

Predictors of advanced proximal neoplasia in persons with abnormal screening flexible sigmoidoscopy.

BACKGROUND & AIMS: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. RESULTS: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>or=10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. CONCLUSIONS: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia.

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PubMed2002

Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial.

Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.

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PubMedDate not supplied

The prostate, lung, colon, and ovarian (PLCO) cancer screening trial: Status and promise.

The Prostate, Lung, Cancer, and Ovarian Cancer Screening Trial is a randomized, multicenter, study evaluating whether screening for prostate, lung, colon, and ovarian cancer will reduce cancer-specific mortality. More than 155,000 participants have been identified and will be monitored through 2015. A biorepository of screened individuals and control participants has been created. Together, the data derived from the intervention and control arms and material in the biorepository provide a valuable resource to allow identification and testing of novel biomarkers for human disease.

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