Results From Four Rounds of Ovarian Cancer Screening in a Randomized Trial

University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA.
Obstetrics and Gynecology (Impact Factor: 5.18). 05/2009; 113(4):775-82. DOI: 10.1097/AOG.0b013e31819cda77
Source: PubMed


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.,, NCT00002540

Download full-text


Available from: Christine C Johnson,
  • Source
    • "There are four large ovarian cancer screening trials reported that have TVS as a major component of the screening algorithm (Table 2). The Prostate, Lung, Colorectal and Ovarian (PLCO) trial in the US was a randomized controlled trial of 78,216 women aged 55–74 years assigned to receive either annual screening with TVS and serum Ca-125 for 4 years or their usual gynecologic care.25,26 Ultrasound findings considered abnormal included: 1) an ovarian volume >10 cm3, 2) an ovarian cyst volume >10 cm3, 3) any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size, or 4) any mixed (solid and cystic) component within a cystic ovarian tumor. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Transvaginal ultrasonography (TVS) is an integral part of all major ovarian cancer screening trials. TVS is accurate in detecting abnormalities in ovarian volume and morphology, but is less reliable in differentiating benign from malignant ovarian tumors. When used as the only screening test, TVS is sensitive, but has a low positive predictive value. Therefore, serum biomarkers and tumor morphology indexing are used together with TVS to identify ovarian tumors at high risk for malignancy. This allows preoperative triage of high-risk cases to major cancer centers for therapy while decreasing unnecessary surgery for benign disease. Ovarian cancer screening has been associated with a decrease in stage at detection in most trials, thereby allowing treatment to be initiated when the disease is most curable.
    International Journal of Women's Health 12/2013; 6(1):25-33. DOI:10.2147/IJWH.S38347
  • Source
    • "When ovarian cancer is detected early, the five year survival rate is over 90% [4]. Serum measurement of CA125, the current standard, has an early stage detection rate of only about 28% and when combined with ultrasound still only identifies 48% [5,6]. Development of improved diagnostic tools for early detection of ovarian cancer, including the discovery of new ovarian cancer biomarkers, has the potential to significantly improve the survival rate. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. CA125 is currently used as the marker for ovarian cancer; however, it lacks specificity and sensitivity for detecting early stage disease. There is a critical unmet need for sensitive and specific routine screening tests for early diagnosis that can reduce ovarian cancer lethality by reliably detecting the disease at its earliest and treatable stages. Results In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/−) treatment confirmed the sialylation changes in the ovarian cancer samples. Conclusion Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer.
    Clinical Proteomics 08/2012; 9(1):10. DOI:10.1186/1559-0275-9-10
  • Source
    • "Previous attempts at screening for ovarian cancer, in the hope of, at minimum, intercepting the development of the disease at an early stage, have largely been unsuccessful. In one large multi-institutional prospective study of 35000 women screened with CA-125 and transvaginal ultrasounds, 70% of the women presented with advanced stage disease, which was no different from unscreened populations [86]. This suggests that cancer prevention should probably play a larger role if there is to be success in reducing ovarian-cancer related mortality. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.
    Journal of Hematology & Oncology 03/2012; 5(1):8. DOI:10.1186/1756-8722-5-8 · 4.81 Impact Factor
Show more