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

PRIMARY OBJECTIVES:

I. To determine whether screening with digital rectal examination (DRE) plus serum
prostate-specific antigen (PSA) can reduce mortality from prostate cancer in men 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 (Prostate Screening): Participants undergo blood sample collection for PSA analysis at
baseline and annually for 5 years. Serum that is not used in the study will be stored in an
NCI biorepository. Participants also undergo a DRE 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 prostate
cancer (follow-up diagnostic procedures are through their own medical care environment).
Participants diagnosed with prostate 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 prostate cancers 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:

- Men 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, prostate

- This includes primary or metastatic PLCO cancers

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

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

- Males who have taken Proscar/Propecia/finasteride in the past 6 months

- NOTE: Individuals who are already enrolled in the trial when their physician
prescribes finasteride are not prevented from taking this medication. As a
result, these participants will continue to be screened and followed just as
those participants who are not on finasteride.

- NOTE: Men who are taking Tamoxifen are not excluded from any part of the PLCO
Screening Trial.

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

- Males who have had more than one PSA blood test in the past three years

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