After nearly 12 years of follow-up, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial has shown that screening with flexible sigmoidoscopy reduces colorectal-cancer incidence by 21% ...and mortality by 26%.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States.
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Colorectal-cancer mortality
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and incidence
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,
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are reduced with screening by means of fecal occult-blood testing. Endoscopic screening with flexible sigmoidoscopy or colonoscopy is more sensitive than fecal testing for the detection of adenomatous polyps, the precursor lesions of colorectal cancer.
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Three European randomized trials of flexible sigmoidoscopy have been performed.
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In the United Kingdom, one-time screening with flexible sigmoidoscopy significantly reduced the incidence of colorectal cancer (by 23%) and associated mortality (by 31%).
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In Italy, an 18% reduction in incidence and a nonsignificant 22% . . .
CONTEXT Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. OBJECTIVE To evaluate the effect of screening for ovarian cancer ...on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial of 78 216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39 105) or usual care (n = 39 111) at 10 screening centers across the United States between November 1993 and July 2001. INTERVENTION The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median range, 12.4 years 10.9-13.0 years) for cancer diagnoses and death until February 28, 2010. MAIN OUTCOME MEASURES Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. RESULTS Ovarian cancer was diagnosed in 212 women (5.7 per 10 000 person-years) in the intervention group and 176 (4.7 per 10 000 person-years) in the usual care group (rate ratio RR, 1.21; 95% confidence interval CI, 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10 000 person-years) in the intervention group and 100 deaths (2.6 per 10 000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10 000 person-years) in the intervention group and 2914 deaths (76.2 per 10 000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). CONCLUSIONS Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00002540
Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial.
This was a randomized controlled trial of screening ...versus usual care. Baseline screening results are reported.
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.
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.
CONTEXT The effect on mortality of screening for lung cancer with modern chest radiographs is unknown. OBJECTIVE To evaluate the effect on mortality of screening for lung cancer using radiographs in ...the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial that involved 154 901 participants aged 55 through 74 years, 77 445 of whom were assigned to annual screenings and 77 456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed. INTERVENTION Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009. MAIN OUTCOME MEASURES Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality. RESULTS Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10 000 person-years in the intervention group and 19.2 per 10 000 person-years in the usual care group (rate ratio RR; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10). CONCLUSION Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00002540
The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research ...by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses' Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.
In this study involving nearly 77,000 men, investigators analyzed the effect of screening with prostate-specific–antigen testing and digital rectal examination on the rate of death from prostate ...cancer, as compared with usual care. After a follow-up of 7 years, the death rates from prostate cancer did not differ significantly between the two study groups. Data from the 10-year follow-up (which were 67% complete) also showed no significant difference in prostate-cancer mortality.
The benefit of screening for prostate cancer with serum prostate-specific–antigen (PSA) testing, digital rectal examination, or any other screening test is unknown. There has been no comprehensive assessment of the trade-offs between benefits and risks. Despite these uncertainties, PSA screening has been adopted by many patients and physicians in the United States and other countries. The use of PSA testing as a screening tool has increased dramatically in the United States since 1988.
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Numerous observational studies have reported conflicting findings regarding the benefit of screening.
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As a result, the screening recommendations of various organizations differ. The American Urological Association and . . .
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.
Background
The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality ...from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
Methods
A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results
Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P
interaction = .81), pretrial PSA testing (P
interaction = .52), and comorbidity (P
interaction = .68).
Conclusions
After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly ...used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.
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