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
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
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.
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 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with ...early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers. Methods A total of 77 464 participants, aged 55–74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided. Results Compliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%–7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (Ptrend < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non–small cell lung cancers. Among non–small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I–II) stage. Conclusions The PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.
To test whether annual screening with transvaginal ultrasonography and CA 125 reduces ovarian cancer mortality.
Data from the first four annual screens, denoted T0-T3, are reported. A CA 125 value at ...or above 35 units/mL or an abnormality on transvaginal ultrasonography was considered a positive screen. Diagnostic follow-up of positive screens was performed at the discretion of participants' physicians. Diagnostic procedures and cancers were tracked and verified through medical records.
Among 34,261 screening arm women without prior oophorectomy, compliance with screening ranged from 83.1% (T0) to 77.6% (T3). Screen positivity rates declined slightly with transvaginal ultrasonography, from 4.6 at T0 to 2.9-3.4 at T1-T3; CA 125 positivity rates (range 1.4-1.8%) showed no time trend. Eighty-nine invasive ovarian or peritoneal cancers were diagnosed; 60 were screen detected. The positive predictive value (PPV) and cancer yield per 10,000 women screened on the combination of tests were similar across screening rounds (range 1.0-1.3% for PPV and 4.7-6.2 for yield); however, the biopsy (surgery) rate among screen positives decreased from 34% at T0 to 15-20% at T1-T3. The overall ratio of surgeries to screen-detected cancers was 19.5:1. Seventy-two percent of screen-detected cases were late stage (III/IV).
Through four screening rounds, the ratio of surgeries to screen-detected cancers was high, and most cases were late stage. However, the effect of screening on mortality is as yet unknown.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00002540
II.
Objective The purpose of this study was to measure the occurrence and natural history of simple ovarian cysts in a cohort of older women. Study Design Simple cysts were ascertained among a cohort of ...15,735 women from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial through 4 years of transvaginal ultrasound screening. Results Simple cysts were seen in 14% of women the first time that their ovaries were visualized. The 1-year incidence of new simple cysts was 8%. Among ovaries with 1 simple cyst at the first screen, 54% retained 1 simple cyst, and 32% had no cyst 1 year later. Simple cysts did not increase risk of subsequent invasive ovarian cancer. Conclusion Simple ovarian cysts are fairly common among postmenopausal women, and most cysts appear stable or resolve by the next annual examination. These findings support recent recommendations to follow unilocular simple cysts in postmenopausal women without intervention.
Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and
body mass index (BMI). It has been recently proposed that this relationship ...may be explained by the larger plasma volume of
obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in
the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening,
28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline.
Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration
times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration,
plasma volume, PSA mass, and BMI.
Results: PSA concentration significantly decreased with increasing BMI ( P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese
(BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and
PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories
( P = 0.10).
Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained
by a hemodilution effect. These findings could have implications for prostate cancer screening in large men. (Cancer Epidemiol
Biomarkers Prev 2009;18(3):748–51)
Abstract Objective To determine the epidemiology of CA-125 in women without ovarian cancer. Methods We analyzed demographic, medical and lifestyle characteristics related to CA-125, measured using ...the Centocor CA-125II RIA assay, among 25,608 multi-ethnic U.S. women aged 55–74 years enrolled in a cancer screening trial and found to have no evidence of ovarian cancer. Results Mean CA-125 level was 11.9 U/ml (SD 8.3); median 10.0 U/ml, interquartile range 8.0–14.0. High levels, using the clinical cut point of ≥ 35 U/ml, were associated with increased age ( p < 0.001) and former smoking ( p < 0.021), while hysterectomy and obesity were protective ( p < 0.001). Mean levels were higher with increasing age ( p < 0.001), ever use of hormone therapy ( p < 0.001), former smoking ( p < 0.017) and history of breast cancer ( p < 0.002), but lower ( p < 0.001) with non-White status, previous hysterectomy, current smoking, and obesity. Current hormone therapy use was not associated with CA-125 in women without a uterus. Conclusion In post-menopausal women without ovarian cancer, CA-125 level is influenced by a number of factors, including race/ethnicity, age, hysterectomy, smoking history and obesity.
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.
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