Ovarian Carcinoma, Ovarian Germ Cell Tumor
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 ovarian cancer. The ovarian cancer screening tests are part of a trial that addresses the screening of four cancer sites, each with their own results record: prostate (NCT00002540), lung (NCT01696968), colorectal (NCT01696981), and ovarian (NCT01696994).
Detailed description
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Undergo questionnaire assessments
PROCEDUREUltrasound Imaging
Undergo TVU
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 74 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers) | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Ovarian cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate. |
| Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers) | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Ovarian 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 |
|---|---|---|
| T3 TVU Screening Results | T3 (three years after entry) | Transvaginal Ultrasound (TVU) result. |
| T4 CA-125 Screening Results | T4 (four years after entry) | Cancer Antigen 125 (CA-125) result. |
| Deaths From All Causes | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. |
| Death Rates From All Causes | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study. |
| Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers) | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Ovarian cancer diagnoses confirmed by medical record abstraction. |
| Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers). | Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years. | Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer. |
| T5 CA-125 Screening Results | T5 (five years after entry) | Cancer Antigen 125 (CA-125) result. |
| T0 (Baseline) CA-125 Screening Results | T0 (at study entry) | Cancer Antigen 125 (CA-125) result. |
| T0 (Baseline) TVU Screening Results | T0 (at study entry) | Transvaginal Ultrasound (TVU) result. |
| T1 CA-125 Screening Results | T1 (one year after entry) | Cancer Antigen 125 (CA-125) result. |
| T1 TVU Screening Results | T1 (one year after entry) | Transvaginal Ultrasound (TVU) result. |
| T2 CA-125 Screening Results | T2 (two years after entry) | Cancer Antigen 125 (CA-125) result. |
| T2 TVU Screening Results | T2 (one year after entry) | Transvaginal Ultrasound (TVU) result. |
| Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | One year from screening examination | Number of positive screens with complications |
| T3 CA-125 Screening Results | T3 (three years after entry) | Cancer Antigen 125 (CA-125) result. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled between November 1993 and July 2001 at 10 study centers.
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. Participants complete a baseline questionnaire (BQ) at entry and a dietary history questionnaire (DHQ) during study years 0-6. | 39,111 |
| Ovarian Screening Participants undergo blood sample collection for Cancer Antigen 125 (CA-125) analysis at baseline and annually for 5 years. Participants also undergo an OVR (discontinued in December 1998) and TVU at baseline and annually for 3 years. | 39,105 |
| Total | 78,216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cancer Before Rand. (Ovarian Screening) | 0 | 2 |
| Overall Study | Died Before ASU (Control) | 73 | 0 |
| Overall Study | Died Before Randomization | 1 | 2 |
| Overall Study | No Ovaries at Baseline | 4,807 | 4,851 |
| Overall Study | Refused ASU (Control) | 311 | 0 |
| Overall Study | Refused Screen (Ovarian Screening) | 0 | 3,582 |
Baseline characteristics
| Characteristic | Ovarian Screening | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13872 Participants | 13889 Participants | 27761 Participants |
| Age, Categorical Between 18 and 65 years | 25233 Participants | 25222 Participants | 50455 Participants |
| Age, Continuous | 62.5 years STANDARD_DEVIATION 5.4 | 62.5 years STANDARD_DEVIATION 5.4 | 62.5 years STANDARD_DEVIATION 5.4 |
| Region of Enrollment United States | 39105 participants | 39111 participants | 78216 participants |
| Sex: Female, Male Female | 39105 Participants | 39111 Participants | 78216 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 903 / 34,253 |
| serious Total, serious adverse events | 0 / 34,253 |
Outcome results
Primary
Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers)
Ovarian 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 11.9 years.
Population: Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers) | 2.6 Deaths per 10,000 PY |
| Ovarian Screening | Ovarian Cancer Death Rates (Including Primary Peritoneal and Fallopian Tube Cancers) | 3.1 Deaths per 10,000 PY |
95% CI: [0.91, 1.54]Poisson regression
Primary
Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers)
Ovarian 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 11.9 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers) | 100 Participants |
| Ovarian Screening | Ovarian Cancer Deaths (Including Primary Peritoneal and Fallopian Tube Cancers) | 188 Participants |
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, she 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 Ovarian Cancer Diagnosis | 49 Positive screens w/ complications |
| Control | Complications of Diagnostic Evaluation (DE) Following a Positive Screening Test | When DE Did Not Lead to Ovarian Cancer Diagnosis | 226 Positive screens w/ complications |
Secondary
Death Rates From All Causes
Deaths from all causes were compared between the ovarian 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; median follow-up 11.9 years.
Population: Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Death Rates From All Causes | 92.6 Deaths per 10,000 PY |
| Ovarian Screening | Death Rates From All Causes | 91.9 Deaths per 10,000 PY |
95% CI: [0.95, 1.04]Poisson regression
Secondary
Deaths From All Causes
Deaths from all causes were compared between the ovarian cancer screening arm and the usual care arm.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Deaths From All Causes | 3542 Participants |
| Ovarian Screening | Deaths From All Causes | 3508 Participants |
Secondary
Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers)
Ovarian cancer diagnoses confirmed by medical record abstraction.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
Population: Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers) | 176 Participants |
| Ovarian Screening | Ovarian Cancer Incidence (Including Primary Peritoneal and Fallopian Tube Cancers) | 212 Participants |
Secondary
Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers).
Ovarian cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as ovarian cancer diagnoses divided by person years at risk for ovarian cancer.
Time frame: Events through 13 years of follow-up or through December 31, 2009; median follow-up 11.9 years.
Population: Female participants, excluding females without ovaries at baseline, were analyzed. An intention-to-treat analysis was performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers). | 4.7 Diagnoses per 10,000 PY |
| Ovarian Screening | Ovarian Cancer Incidence Rates (Including Primary Peritoneal and Fallopian Tube Cancers). | 5.7 Diagnoses per 10,000 PY |
95% CI: [0.99, 1.48]Poisson regression
Secondary
T0 (Baseline) CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T0 (at study entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T0 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T0 (Baseline) CA-125 Screening Results | Negative (<35 U/mL) | 28275 Participants |
| Control | T0 (Baseline) CA-125 Screening Results | Positive (>= 35 U/mL) | 400 Participants |
| Control | T0 (Baseline) CA-125 Screening Results | Inadequate screen | 58 Participants |
Secondary
T0 (Baseline) TVU Screening Results
Transvaginal Ultrasound (TVU) result.
Time frame: T0 (at study entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T0 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T0 (Baseline) TVU Screening Results | Negative | 26624 Participants |
| Control | T0 (Baseline) TVU Screening Results | Positive | 1309 Participants |
| Control | T0 (Baseline) TVU Screening Results | Inadequate screen | 544 Participants |
Secondary
T1 CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T1 (one year after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T1 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T1 CA-125 Screening Results | Negative (<35 U/mL) | 27035 Participants |
| Control | T1 CA-125 Screening Results | Positive (>= 35 U/mL) | 433 Participants |
| Control | T1 CA-125 Screening Results | Inadequate screen | 46 Participants |
Secondary
T1 TVU Screening Results
Transvaginal Ultrasound (TVU) result.
Time frame: T1 (one year after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T1 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T1 TVU Screening Results | Negative | 25740 Participants |
| Control | T1 TVU Screening Results | Positive | 930 Participants |
| Control | T1 TVU Screening Results | Inadequate screen | 376 Participants |
Secondary
T2 CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T2 (two years after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T2 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T2 CA-125 Screening Results | Negative (<35 U/mL) | 26024 Participants |
| Control | T2 CA-125 Screening Results | Positive (>= 35 U/mL) | 480 Participants |
| Control | T2 CA-125 Screening Results | Inadequate screen | 51 Participants |
Secondary
T2 TVU Screening Results
Transvaginal Ultrasound (TVU) result.
Time frame: T2 (one year after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T2 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T2 TVU Screening Results | Negative | 24988 Participants |
| Control | T2 TVU Screening Results | Positive | 764 Participants |
| Control | T2 TVU Screening Results | Inadequate screen | 296 Participants |
Secondary
T3 CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T3 (three years after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T3 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T3 CA-125 Screening Results | Negative (<35 U/mL) | 24925 Participants |
| Control | T3 CA-125 Screening Results | Positive (>= 35 U/mL) | 427 Participants |
| Control | T3 CA-125 Screening Results | Inadequate screen | 49 Participants |
Secondary
T3 TVU Screening Results
Transvaginal Ultrasound (TVU) result.
Time frame: T3 (three years after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a TVU screen at T3 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T3 TVU Screening Results | Inadequate screen | 290 Participants |
| Control | T3 TVU Screening Results | Negative | 23926 Participants |
| Control | T3 TVU Screening Results | Positive | 733 Participants |
Secondary
T4 CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T4 (four years after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T4 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T4 CA-125 Screening Results | Negative (<35 U/mL) | 19772 Participants |
| Control | T4 CA-125 Screening Results | Positive (>= 35 U/mL) | 327 Participants |
| Control | T4 CA-125 Screening Results | Inadequate screen | 16 Participants |
Secondary
T5 CA-125 Screening Results
Cancer Antigen 125 (CA-125) result.
Time frame: T5 (five years after entry)
Population: Females in the Ovarian Screening arm (excluding females with no ovaries at baseline) who had a CA-125 screen at T5 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control | T5 CA-125 Screening Results | Negative (<35 U/mL) | 21788 Participants |
| Control | T5 CA-125 Screening Results | Positive (>= 35 U/mL) | 366 Participants |
| Control | T5 CA-125 Screening Results | Inadequate screen | 39 Participants |