<b>CONTEXT: </b>Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality.<b>OBJECTIVE: </b>To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.<b>Design, Setting, and Participants: </b>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.<b>MAIN OUTCOME MEASURES: </b>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.<b>RESULTS: </b>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).<b>CONCLUSIONS: </b>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 is common in women from developed countries. We designed a prospective randomized controlled trial of ovarian cancer screening to establish an improved strategy for the early detection of cancers. Asymptomatic postmenopausal women were randomly assigned between 1985 and 1999 to either an intervention group (n = 41,688) or a control group (n = 40,799) in a ratio of 1:1, with follow-up of mean 9.2 years, in Shizuoka district, Japan. The original intention was to offer women in the intervention group annual screens by gynecological examination (sequential pelvic ultrasound [US] and serum CA125 test). Women with abnormal US findings and/or raised CA125 values were referred for surgical investigation by a gynecological oncologist. In December 2002, the code was broken and the Shizuoka Cohort Study of Ovarian Cancer Screening and Shizuoka Cancer Registry were searched to determine both malignant and nonmalignant diagnoses. Twenty-seven cancers were detected in the 41,688-screened women. Eight more cancers were diagnosed outside the screening program. Detection rates of ovarian cancer were 0.31 per 1000 at the prevalent screen and 0.38-0.74 per 1000 at subsequent screens; they increased with successive screening rounds. Among the 40,779 control women, 32 women developed ovarian cancer. The proportion of stage I ovarian cancer was higher in the screened group (63%) than in the control group (38%), which did not reach statistical significance (P = 0.2285). This is to our knowledge the first prospective randomized report of the ovarian cancer screening. The rise in the detection of early-stage ovarian cancer in asymptomatic postmenopausal women is not significant, but future decisions on screening policy should be informed by further follow-up from this trial.
While ovarian cancer is rare and screening is not recommended for most women, it is being studied as a way to reduce ovarian cancer mortality. As effective strategies for screening emerge it will be important to understand the quality of life (QOL) effects of participation in ovarian cancer screening. In this study, we examined the effects of participation in an ovarian cancer screening program on worry about cancer risk and QOL. A randomized controlled clinical trial (n = 592) was conducted. Women without a family history suggestive of a BRCA1/2 mutation were randomly assigned to screening and risk counseling, separately and in combination. Results were compared to women randomized to usual care alone. Levels of cancer worry fell for all study groups and QOL was unaffected; no statistically significant differences were found between groups. Increased levels of worry about ovarian cancer at 2-year follow-up were found among participants in screening receiving abnormal test results. For those who receive abnormal results, screening may have long-term effects and increase worry about cancer risk. Further research will be required to examine the possibility that screening reduces worry when women receive only normal, presumably reassuring, results. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
PURPOSE: To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile.
PATIENTS AND METHODS: Postmenopausal women, > or = 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion.
RESULTS: Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively.
CONCLUSION: An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.
BACKGROUND: The National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was designed to examine whether annual screening tests for these four tumor sites result in reduced disease-related mortality. We assessed the impact of trial participation on both health-related quality of life (HRQL) and trial adherence.
METHODS: Participants (N = 432; 217 in the control arm and 215 in screening arm) were accrued from the Georgetown University PLCO site from May through December 1998. Screening-arm participants were interviewed by telephone at baseline (prescreening), shortly after notification of screening results (short-term follow-up), and 9 months after notification of screening results (intermediate-term follow up). Control-arm participants completed a baseline and 1-year follow-up assessment. Logistic regression analyses were conducted.
RESULTS: Participants reported high levels of HRQL and satisfaction with their decision to participate. Screening-arm participants with abnormal screening results had a higher level of intrusive thoughts about cancer than those with all normal results (odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.3 to 6.3) at the short-term follow-up but not at the intermediate-term follow-up (when abnormal test results were known to be false positive; OR = 1.9, 95% CI = 0.89 to 4.2). Trial adherence was statistically significantly better among participants who had received all normal results in the previous year's screening tests (93.7% versus 78.7%; OR = 3.7, CI = 1.1 to 12.0) than in those who received at least one abnormal result. In the control arm, adherence (defined as returning annual questionnaires) was positively associated with education (OR = 3.4, 95% CI = 1.4 to 8.4) and sex, with women being more likely to return questionnaires than men (OR = 2.1, 95% CI = 1.05 to 4.4).
CONCLUSIONS: It is feasible to collect HRQL measures as part of a large cancer screening trial. Prior abnormal screening results were related to short-term HRQL but not to intermediate-term HRQL. Trial adherence was poorer among those who had received previous false-positive results. These results suggest several methods for improving adherence in this and other subgroups.
BACKGROUND: The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography.
METHODS: Postmenopausal women aged 45 years or older were randomised to a control group (n=10,977) or screened group (n=10,958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8.8 mL or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers).
FINDINGS: Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had false-positive screening results. The positive predictive value was 20.7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (p=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10,977 vs nine of 10,958, relative risk 2.0 [95% CI 0.78-5.13]).
INTERPRETATION: These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible and justify a larger randomised trial to see whether screening affects mortality.
OBJECTIVES: To assess the feasibility of a randomised trial of ovarian cancer screening by vaginal ultrasonography.
SETTING: A population based study, recruiting a random sample of the female population aged 46 to 65 years living in Copenhagen, Denmark.
DESIGN: Randomised controlled trial allocating 50% to the study group having vaginal ultrasonography, and 50% to the control group having no examination. (a) Acceptability of the study was evaluated by the proportion of eligible women willing to participate in the study. (b) The false positive rate was evaluated as the proportion of women without ovarian cancer referred for an operation because of abnormal ovaries detected by ultrasonography.
RESULTS: 950 (64.3%) of the 1477 eligible women participated in the study. At the first scan abnormal ovaries were detected in 54 of 435 women (12%), significantly more frequently among younger women. Nine women were referred for an operation because of abnormal findings in the ovaries, giving a false positive rate of 2%. Ovarian size and morphology found at operation corresponded with those at ultrasonography; none of them was malignant.
CONCLUSIONS: A randomised controlled trial of ovarian cancer screening using vaginal ultrasonography seems acceptable in the general population. The rate of abnormal ovaries at ultrasonography with the cut offs used in this study was quite high. Such a study is, therefore, feasible, but it is proposed that it is carried out in an older age group (50-64 years) and that the cut offs used for ovarian size and morphology are re-evaluated. Second line tests, such as colour Doppler flow, should be considered in order to reduce the false positive rate.
OBJECTIVE: To determine the feasibility of a randomised trial of ovarian cancer screening among women attending a breast cancer screening centre.
DESIGN: Randomised controlled trial of ovarian cancer screening using transvaginal ultrasonography as a primary screening test and colour Doppler imaging as a secondary screening test in the screened group and no intervention in the control group.
SETTING: Reading breast cancer screening centre (United Kingdom).
SUBJECTS: 8678 women, without a bilateral oophorectomy or hysterectomy, aged between 50 and 64 attending for NHS breast cancer screening between September 1989 and February 1993.
MAIN OUTCOME MEASURES: Uptake of ovarian cancer screening among eligible women and the screening false positive rate (considered as the referral rate to a gynaecologist for surgical intervention).
RESULTS: 82% (7124/8678) of eligible women agreed to join the trial and were randomly allocated in equal numbers to each arm of the trial. 3280 women had an initial scan. The false positive rate after ultrasonography alone was 2.9% (86/2952), but this dropped to 0.5% after colour Doppler as a secondary screening test. One stage I primary ovarian cancer was detected at screening in a 58 year old women.
CONCLUSIONS: A randomised trial of ovarian cancer screening using ultrasonography and colour Doppler imaging is feasible and acceptable among women attending a breast cancer screening centre. The results indicate that the expected odds of being affected given a positive result in the general population would be about 1:12. A full randomised trial of ovarian cancer screening with mortality as the end point is needed to assess whether screening reduces mortality from this disease. A multicentre European trial is currently in progress.
