CA125 and Ultrasound in Detecting Ovarian Cancer in Postmenopausal Women

University College, London202,638 enrolled

Overview

RATIONALE: Screening tests may help doctors detect ovarian cancer early when the survival is much more encouraging. It is not yet known whether a CA125-based or ultrasound strategy is more effective in detecting ovarian cancer early thereby impacting on the mortality from the disease in postmenopausal women from the general population. PURPOSE: Randomized clinical trial to assess the impact of screening using a multimodal strategy using CA125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA) followed by transvaginal ultrasound as a second line test versus transvaginal ultrasound on mortality from the disease in postmenopausal women from the general population.

OBJECTIVES: * Determine the impact of preclinical detection of ovarian cancer by screening on ovarian cancer mortality in postmenopausal women. * Determine the physical morbidity of ovarian cancer screening in this population. * Determine the psychological consequences of screening results (true negative, true positive, false negative, and false positive) in this population. * Compare the interventions that result from screening for ovarian cancer using CA 125 monitoring and ultrasound in this population. * Compare the feasibility of population screening, in terms of compliance rates with annual screening for ovarian cancer with these strategies. * Compare the performance of these screening strategies in this population. OUTLINE: This is a randomized, multicenter study. Participants are randomized to 1 of 3 screening arms. * Arm I: Participants do not undergo screening. * Arm II: Participants undergo screening with an annual CA 125 level interpreted using the Risk of Ovarian Cancer Algorithm (ROCA). Depending on the results of the test, some patients may undergo additional screening. * Arm III: Participants undergo screening with an annual transvaginal or transabdominal ultrasound. Depending on the results of the test, some patients may undergo additional screening. Participants in all arms complete a health questionnaire at 3-5 years after study entry and in 2014. PROJECTED ACCRUAL: A total of 200,000 participants (100,000 for arm I and 50,000 each for arms II and III) will be accrued for this study within 5 years.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Eligibility

Sex: FEMALEMin age: 50 YearsMax age: 74 YearsHealthy volunteers:

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Postmenopausal, as defined by meeting 1 of the following criteria: * More than 12 months of amenorrhea after natural menopause or hysterectomy * Received more than 12 months of hormone replacement therapy for menopausal symptoms * No prior ovarian malignancy * No prior bilateral oophorectomy * Not at high risk for ovarian cancer due to familial predisposition as defined by the UKCCCR Familial Ovarian Cancer Screening Study PATIENT CHARACTERISTICS: Age * 50 to 74 Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * No active non-ovarian malignancy * Prior malignancy allowed provided there is no documented persistent or recurrent disease and patient has not received treatment for more than 1 year PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * See Disease Characteristics Radiotherapy * Not specified Surgery * See Disease Characteristics Other * No concurrent participation in any other ovarian cancer screening study

Outcomes

Primary Outcomes

UKCTOCS (2001-2014): Death due to ovarian cancer (WHO 2003) determined by independent outcomes committee review of patient notes for all women identified to have a 'possible ovarian cancer' (pre-specified ICD-10 codes) till 31st December 2014.

Long term impact of screening on ovarian cancer mortality in the UKCTOCS (LTFU UKCTOCS) (2015-2021): Death due to ovarian cancer (WHO 2014) determined by independent outcomes committee review till 30 June 2020.

Secondary Outcomes

Performance characteristics: Sensitivity, specificity, positive predictive values of the two screening strategies (multimodal and ultrasound) for detection of ovarian cancer diagnosed within one year of last screen.

Ovarian cancer diagnosis is based on outcomes review of medical notes of all women who developed ovarian cancer during the trial.

Surgical complications in women who underwent false positive surgery and were found to have benign or normal adnexae.

This is assessed through central medical note review and assigned by designated trial gynaecological oncologist.

Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm.

Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm: (a) Incremental cost-effectiveness analysis over the 14 year period of the trial (censorship 31st Dec 2014); (b) Incremental cost-effectiveness analysis for the cumulative mortality estimated over a 25-year period by extrapolating beyond the 14 years of the trial

Compliance with annual screening: The proportion of women who attended all tests that formed part of an annual screening episode of the total who were eligible for that annual screening episode.

Psychological morbidity related to screening - assessed in a separate MRC funded study, UKCTOCS Psychosocial study, PI Prof Dame Lesley Fallowfield.