Screening for Ovarian Cancer in Older Patients (PLCO Screening Trial)

PRIMARY OBJECTIVES:

I. To determine whether screening with CA125 and transvaginal ultrasound (TVU) can reduce
mortality from ovarian cancer in women aged 55-74 at entry.

SECONDARY OBJECTIVES:

I. To assess screening variables, other than mortality, for each of the interventions
including sensitivity, specificity, and positive predictive value.

II. To assess the incidence, stage, and survival of cancer cases. III. To investigate the
mortality predictive value of biologic and/or prognostic characterizations of tumor tissue as
intermediate endpoints.

IV. To conduct biomolecular and genetic research into factors associated with cancer
carcinogenesis and promotion, as well as the early detection of these factors.

OUTLINE: Participants in the overall PLCO study are stratified by screening center, gender,
and age (55-59 vs 60-64 vs 65-69 vs 70-74). Participants are randomized to 1 of 2 arms
(control vs screening).

ARM I (Control): Participants receive standard medical care. Participants complete a Diet
History Questionnaire (DHQ) at baseline.

ARM II (Ovarian Screening): Participants undergo blood sample collection for CA125 analysis
at baseline annually for 5 years. Serum that is not used in the study will be stored in an
NCI biorepository. Participants also undergo an ovarian palpation exam (OVR, discontinued in
December 1998) and TVU at baseline and annually for 3 years. A scheduling and tracking
procedure is implemented to ensure regular attendance at repeat screens for participants
screened negative or for those who are designated suspicious or positive at screening but for
whom subsequent diagnostic procedures do not reveal ovarian cancer (follow-up diagnostic
procedures are through their own medical care environment). Participants diagnosed with
ovarian cancer via a screening test are referred for treatment in accordance with current
accepted practice for appropriate stage of disease, patient age, and medical condition; a
procedure is provided for contact with qualified medical personnel to insure appropriate
therapy.

Participants complete a Dietary Questionnaire (DQX) at baseline and DHQ at year 3. An Annual
Study Update (ADU) (previously referred to as the Periodic Survey of Health [PSH]
questionnaire) is mailed to each participant annually for 13 years to identify all prevalent
and incident cancers of the ovaries as all deaths that occur among both screened and control
subjects during the trial.

After completion of screening, participants are followed up for at least 13 years.

Exclusion Criteria:

- Women who at the time of randomization are less than 55 or greater than or equal to 75
years of age

- Individuals undergoing treatment for cancer at this time, excluding basal-cell and
squamous-cell skin cancer

- Individuals with known prior cancer of the colon, rectum, lung, or ovary

- This includes primary or metastatic PLCO cancers

- Individuals with previous surgical removal of the entire colon or one lung

- Until October 1996, women with previous surgical removal of both ovaries were
excluded from the trial. In order to increase the enrollment of women into the
trial, beginning in October 1996, these women were no longer excluded for this
reason.

- Individuals who are participating in another cancer screening or cancer primary
prevention trial

- Prior to April 1, 1999 women were excluded from the trial if they were currently
taking or had taken Tamoxifen or Evista\Raloxifene in the past 6 months. As of April
1999 based on a decision from the PLCO Ovary Subcommittee, women who have or are
currently taking Tamoxifen or Evista\Raloxifene are not excluded from participation.

- Individuals who are unwilling or unable to sign the informed consent form

- Individuals who have had a colonoscopy, sigmoidoscopy, or barium enema in the past
three years