Prostate Carcinoma
Conditions
Brief summary
This clinical trial studies whether screening methods used to diagnose cancer of the prostate, lung, colon, rectum, or ovaries can reduce deaths from these cancers. Screening tests may help doctors find cancer cells early and plan better treatment for prostate cancer.
Detailed description
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREMedical Examination Assessment
Undergo DRE
Undergo questionnaire assessments
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
MALE
Age
55 Years to 74 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Cancer Deaths | Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years. | Prostate cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. |
| Prostate Cancer Death Rates | Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years. | Prostate cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Cancer Incidence | Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years. | Prostate cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as prostate cancer diagnoses divided by person years at risk for prostate cancer. |
| Prostate Cancer Incidence Rates | Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years. | Prostate cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as prostate cancer diagnoses divided by person years at risk for prostate cancer. |
| Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | One year from screening examination | Number of positive screens with complications |
| T0 (Baseline) PSA Screening Results | T0 (at study entry) | Prostate-Specific Antigen (PSA) result. |
| T0 (Baseline) DRE Screening Results | T0 (at study entry) | Digital Rectal Examination (DRE) result. |
| T1 PSA Screening Results | T1 (one year after entry) | Prostate-Specific Antigen (PSA) result. |
| Deaths From All Causes | Events through 13 years of follow-up or through December 31, 2009. | Deaths from all causes were compared between the prostate cancer screening arm and the usual care arm. |
| T2 PSA Screening Results | T2 (two years after entry) | Prostate-Specific Antigen (PSA) result. |
| T2 DRE Screening Results | T2 (two years after entry) | Digital Rectal Examination (DRE) results |
| T3 PSA Screening Results | T3 (three years after entry) | Prostate-Specific Antigen (PSA) result |
| T3 DRE Screening Results | T3 (three years after entry) | Digital Rectal examination (DRE) result |
| T4 PSA Screening Result | T4 (four years after entry) | Prostate-Specific Antigen (PSA) result |
| T5 PSA Screening Results | T5 (five years after entry) | Prostate-Specific Antigen (PSA) result. |
| T1 DRE Screening Results | T1 (one year after entry) | Digital Rectal Examination (DRE) result. |
| Death Rates From All Causes | Events through 13 years of follow-up or through December 31, 2009. | Deaths from all causes were compared between the prostate cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled between November 1993 and July 2001 at 10 study centers. Recruitment was done for all four outcomes of the study (prostate, lung, colorectal and ovarian).
Pre-assignment details
Participants signed a study informed consent prior to being randomized to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Control Participants receive standard medical care. | 38,345 |
| Prostate Screening Participants undergo blood sample collection for prostate specific antigen (PSA) analysis at baseline and annually for 5 years. Participants also undergo a digital rectal examination (DRE) at baseline and annually for 3 years. | 38,340 |
| Total | 76,685 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cancer Before Rand. (Prostate Screening) | 0 | 25 |
| Overall Study | Died Before ASU (Control) | 202 | 0 |
| Overall Study | Died Before Randomization | 2 | 6 |
| Overall Study | Refused ASU (Control) | 597 | 0 |
| Overall Study | Refused Screen (Prostate Screening) | 0 | 2,433 |
Baseline characteristics
| Characteristic | Prostate Screening | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13940 Participants | 13955 Participants | 27895 Participants |
| Age, Categorical Between 18 and 65 years | 24400 Participants | 24390 Participants | 48790 Participants |
| Age, Continuous | 62.7 years STANDARD_DEVIATION 5.3 | 62.7 years STANDARD_DEVIATION 5.3 | 62.7 years STANDARD_DEVIATION 5.3 |
| Region of Enrollment United States | 38340 participants | 38345 participants | 76685 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 38340 Participants | 38345 Participants | 76685 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 546 / 38,340 |
| serious Total, serious adverse events | 0 / 38,340 |
Outcome results
Primary
Prostate Cancer Death Rates
Prostate cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. Rate is the number of deaths divided by person years of follow-up in the study.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Prostate Cancer Death Rates | 3.4 Deaths per 10,000 PY |
| Prostate Screening | Prostate Cancer Death Rates | 3.7 Deaths per 10,000 PY |
95% CI: [0.87, 1.36]Poisson regression
Primary
Prostate Cancer Deaths
Prostate cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years.
Population: All male participants randomized were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Prostate Cancer Deaths | 145 Participants |
| Prostate Screening | Prostate Cancer Deaths | 158 Participants |
95% CI: [0.87, 1.36]Poisson regression
Secondary
Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test
Number of positive screens with complications
Time frame: One year from screening examination
Population: The units analyzed were positive screening exams with documented diagnostic follow-up. If a participant received 3 positive screens with documented follow-up after each one, he would be counted 3 times in the number of units analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | When DE Led to Prostate Cancer Diagnosis | 901 Positive screens w/ complications |
| Control | Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | When DE Did Not Lead to Prostate Cancer Diagnosis | 124 Positive screens w/ complications |
Secondary
Death Rates From All Causes
Deaths from all causes were compared between the prostate cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.
Time frame: Events through 13 years of follow-up or through December 31, 2009.
Population: All male participants were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Death Rates From All Causes | 166.6 Deaths per 10,000 PY |
| Prostate Screening | Death Rates From All Causes | 160.5 Deaths per 10,000 PY |
95% CI: [0.93, 1]Poisson regression
Secondary
Deaths From All Causes
Deaths from all causes were compared between the prostate cancer screening arm and the usual care arm.
Time frame: Events through 13 years of follow-up or through December 31, 2009.
Population: All male participants were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Deaths From All Causes | 7089 Participants |
| Prostate Screening | Deaths From All Causes | 6855 Participants |
Secondary
Prostate Cancer Incidence
Prostate cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as prostate cancer diagnoses divided by person years at risk for prostate cancer.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years.
Population: All male participants randomized were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Prostate Cancer Incidence | 3815 Participants |
| Prostate Screening | Prostate Cancer Incidence | 4250 Participants |
Secondary
Prostate Cancer Incidence Rates
Prostate cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as prostate cancer diagnoses divided by person years at risk for prostate cancer.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.0 years.
Population: All male participants randomized were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Prostate Cancer Incidence Rates | 97.1 Diagnoses per 10,000 PY |
| Prostate Screening | Prostate Cancer Incidence Rates | 108.4 Diagnoses per 10,000 PY |
95% CI: [1.07, 1.17]Poisson regression
Secondary
T0 (Baseline) DRE Screening Results
Digital Rectal Examination (DRE) result.
Time frame: T0 (at study entry)
Population: All males in the Prostate Screening arm who had a DRE screen at T0 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T0 (Baseline) DRE Screening Results | Negative | 30456 Participants |
| Control | T0 (Baseline) DRE Screening Results | Positive | 2481 Participants |
| Control | T0 (Baseline) DRE Screening Results | Inadequate screen | 1192 Participants |
Secondary
T0 (Baseline) PSA Screening Results
Prostate-Specific Antigen (PSA) result.
Time frame: T0 (at study entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T0 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T0 (Baseline) PSA Screening Results | Negative (<=4 ng/mL) | 31507 Participants |
| Control | T0 (Baseline) PSA Screening Results | Positive (> 4 ng/mL) | 2718 Participants |
| Control | T0 (Baseline) PSA Screening Results | Inadequate screen | 22 Participants |
Secondary
T1 DRE Screening Results
Digital Rectal Examination (DRE) result.
Time frame: T1 (one year after entry)
Population: All males in the Prostate Screening arm who had a DRE screen at T1 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T1 DRE Screening Results | Negative | 29311 Participants |
| Control | T1 DRE Screening Results | Positive | 2237 Participants |
| Control | T1 DRE Screening Results | Inadequate screen | 900 Participants |
Secondary
T1 PSA Screening Results
Prostate-Specific Antigen (PSA) result.
Time frame: T1 (one year after entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T1 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T1 PSA Screening Results | Negative (<=4 ng/mL) | 30159 Participants |
| Control | T1 PSA Screening Results | Positive (> 4 ng/mL) | 2502 Participants |
| Control | T1 PSA Screening Results | Inadequate screen | 27 Participants |
Secondary
T2 DRE Screening Results
Digital Rectal Examination (DRE) results
Time frame: T2 (two years after entry)
Population: All males in the Prostate Screening arm who had a DRE screen at T2 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T2 DRE Screening Results | Positive | 2327 Participants |
| Control | T2 DRE Screening Results | Inadequate screen | 733 Participants |
| Control | T2 DRE Screening Results | Negative | 28391 Participants |
Secondary
T2 PSA Screening Results
Prostate-Specific Antigen (PSA) result.
Time frame: T2 (two years after entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T2 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T2 PSA Screening Results | Negative | 29063 Participants |
| Control | T2 PSA Screening Results | Positive (> 4 ng/mL) | 2593 Participants |
| Control | T2 PSA Screening Results | Inadequate screen | 35 Participants |
Secondary
T3 DRE Screening Results
Digital Rectal examination (DRE) result
Time frame: T3 (three years after entry)
Population: All males in the Prostate Screening arm who had a DRE screen at T3 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T3 DRE Screening Results | Inadequate screen | 748 Participants |
| Control | T3 DRE Screening Results | Negative | 27179 Participants |
| Control | T3 DRE Screening Results | Positive | 2317 Participants |
Secondary
T3 PSA Screening Results
Prostate-Specific Antigen (PSA) result
Time frame: T3 (three years after entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T3 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T3 PSA Screening Results | Negative (<=4 ng/mL) | 27814 Participants |
| Control | T3 PSA Screening Results | Positive (> 4 ng/mL) | 2676 Participants |
| Control | T3 PSA Screening Results | Inadequate screen | 43 Participants |
Secondary
T4 PSA Screening Result
Prostate-Specific Antigen (PSA) result
Time frame: T4 (four years after entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T4 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T4 PSA Screening Result | Negative (<=4 ng/mL) | 20362 Participants |
| Control | T4 PSA Screening Result | Positive (> 4 ng/mL) | 1796 Participants |
| Control | T4 PSA Screening Result | Inadequate screen | 12 Participants |
Secondary
T5 PSA Screening Results
Prostate-Specific Antigen (PSA) result.
Time frame: T5 (five years after entry)
Population: All males in the Prostate Screening arm who had a PSA screen at T5 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T5 PSA Screening Results | Negative (<=4 ng/mL) | 23560 Participants |
| Control | T5 PSA Screening Results | Positive (> 4 ng/mL) | 2377 Participants |
| Control | T5 PSA Screening Results | Inadequate screen | 14 Participants |