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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01696981
• Collaborator: (none)
• Enrollment: 154,900
• Location: 1
• Arms: 2

Study Details

Study Description

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 colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colon Carcinoma; Rectal Carcinoma	Other: Screening Questionnaire Administration; Procedure: Sigmoidoscopy	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer in women and men aged 55-74 at study entry.

SECONDARY OBJECTIVES:

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

2. 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.

3. 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 (Colorectal Screening): Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. 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 colorectal cancer (follow-up diagnostic procedures are through their own medical care environment). Participants diagnosed with colorectal 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 colorectal 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Screening
• Official Title: Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
• Actual Study Start Date: Nov 16, 1993
• Actual Primary Completion Date: May 21, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Colorectal Screening Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a DQX at baseline and DHQ at year 3. An ADU (previously referred to as the PSH questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident colorectal cancers as all deaths that occur among both screened and control subjects during the trial.	Other: Screening Questionnaire Administration; Undergo questionnaire assessments; Procedure: Sigmoidoscopy; Undergo a flexible sigmoidoscopy; Other Names: Proctosigmoidoscopy
No Intervention: Control Participants receive standard medical care. Participants complete a DHQ at baseline.

Outcome Measures

Primary Outcome Measures

1. Colorectal Cancer Deaths [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Colorectal cancer deaths confirmed in participants by a death review committee if available, otherwise by death certificate.

2. Colorectal Cancer Death Rates [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Colorectal 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 Outcome Measures

1. Deaths From All Causes [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Deaths from all causes were compared between the colorectal cancer screening arm and the usual care arm.

2. Death Rates From All Causes [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Deaths from all causes were compared between the colorectal cancer screening arm and the usual care arm. Rate is the number of deaths divided by person years of follow-up in the study.

3. Colorectal Cancer Incidence [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Colorectal cancer diagnoses confirmed by medical record abstraction.

4. Colorectal Cancer Incidence Rates [Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.]

   Colorectal cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as colorectal cancer diagnoses divided by person years at risk for colorectal cancer.

5. Complications of Diagnostic Evaluation Following a Positive Screening Test [One year from screening examination]

   Number of participants who experienced complications during diagnostic work-up of a positive colorectal examination.

6. T0 (Baseline) FSG Screening Results [T0 (at study entry)]

   Flexible sigmoidoscopy (FSG) result

7. T3/T5 FSG Screening Result [T3 (three years after entry) or T5 (five years after entry)]

   Flexible sigmoidoscopy (FSG) result

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Exclusion Criteria:

• Men and 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, prostate

• This includes primary or metastatic PLCO cancers

• Individuals with previous surgical removal of the entire colon, one lung, or the entire prostate (men only)

• 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

• 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.

• 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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Christine D Berg, National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01696981
• Other Study ID Numbers: NCI-2012-01757; NCI-2012-01757; CDR0000078532; NCI-P93-0050; PLCO-1; PLCO-Colorectal
• First Posted: Oct 2, 2012
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Carcinoma

Study Results

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 Detail	Participants signed a study informed consent prior to being randomized to a study arm.

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Period Title: Overall Study
STARTED	77455	77445
COMPLETED	76254	67071
NOT COMPLETED	1201	10374

Baseline Characteristics

Arm/Group Title	Control	Colorectal Screening	Total
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.	Total of all reporting groups
Overall Participants	77455	77445	154900
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	49610 64.1%	49634 64.1%	99244 64.1%
>=65 years	27845 35.9%	27811 35.9%	55656 35.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.6 (5.4)	62.6 (5.4)	62.6 (5.4)
Sex: Female, Male (Count of Participants)
Female	39111 50.5%	39105 50.5%	78216 50.5%
Male	38344 49.5%	38340 49.5%	76684 49.5%
Region of Enrollment (participants) [Number]
United States	77455 100%	77445 100%	154900 100%

Outcome Measures

1. Primary Outcome

Title	Colorectal Cancer Deaths
Description	Colorectal 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 12.1 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Participants]	341 0.4%	252 0.3%

2. Secondary Outcome

Title	Deaths From All Causes
Description	Deaths from all causes were compared between the colorectal 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 12.1 years.

Outcome Measure Data

Analysis Population Description

All participants. An intention-to-treat analysis was performed.

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Participants]	11064 14.3%	10835 14%

3. Secondary Outcome

Title	Death Rates From All Causes
Description	Deaths from all causes were compared between the colorectal 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 12.1 years.

Outcome Measure Data

Analysis Population Description

All participants. An intention-to-treat analysis was performed.

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Deaths per 10,000 PY]	127.0	124.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Colorectal Screening
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Colorectal Cancer Incidence
Description	Colorectal cancer diagnoses confirmed by medical record abstraction.
Time Frame	Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.

Outcome Measure Data

Analysis Population Description

All participants. An intention-to-treat analysis was performed.

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Participants]	1287 1.7%	1012 1.3%

5. Secondary Outcome

Title	Colorectal Cancer Incidence Rates
Description	Colorectal cancer diagnoses confirmed by medical record abstraction. Incidence rate (cumulative) defined as colorectal cancer diagnoses divided by person years at risk for colorectal cancer.
Time Frame	Events through 13 years of follow-up or through December 31, 2009; median follow-up 12.1 years.

Outcome Measure Data

Analysis Population Description

All participants. An intention-to-treat analysis was performed.

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Diagnoses per 10,000 PY]	15.2	11.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Colorectal Screening
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Complications of Diagnostic Evaluation Following a Positive Screening Test
Description	Number of participants who experienced complications during diagnostic work-up of a positive colorectal examination.
Time Frame	One year from screening examination

Outcome Measure Data

Analysis Population Description

The units analyzed were positive screening exams with documented diagnostic follow-up. If a participant received 2 positive screens with documented follow-up after each one, he would be counted 2 times in the number of units analyzed.

Arm/Group Title	Colorectal Screening
Arm/Group Description	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	21896
Measure Positive Screens with Follow-up	24976
When DE Led to Colorectal Cancer Diagnosis	58
When DE Did Not Lead to Colorectal Cancer Diag	279

7. Primary Outcome

Title	Colorectal Cancer Death Rates
Description	Colorectal 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 12.1 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Colorectal Screening
Arm/Group Description	Participants receive standard medical care. Participants complete a baseline questionnaire at entry and a dietary history questionnaire (DHQ) during study years 0-6.	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	77455	77445
Number [Deaths per 10,000 PY]	3.9	2.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Colorectal Screening
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.63 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	T0 (Baseline) FSG Screening Results
Description	Flexible sigmoidoscopy (FSG) result
Time Frame	T0 (at study entry)

Outcome Measure Data

Analysis Population Description

All participants in the Colorectal Screening arm who had an FSG at T0 were analyzed.

Arm/Group Title	Colorectal Screening
Arm/Group Description	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	64653
Negative	42403 54.7%
Positive	15154 19.6%
Inadequate screen	7096 9.2%

9. Secondary Outcome

Title	T3/T5 FSG Screening Result
Description	Flexible sigmoidoscopy (FSG) result
Time Frame	T3 (three years after entry) or T5 (five years after entry)

Outcome Measure Data

Analysis Population Description

All participants in the Colorectal Screening arm who had an FSG at T0 or T3 were analyzed.

Arm/Group Title	Colorectal Screening
Arm/Group Description	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
Measure Participants	41858
Negative	26694 34.5%
Positive	9818 12.7%
Inadequate screen	5346 6.9%

Adverse Events

Time Frame	During each annual screening visit.
Adverse Event Reporting Description	These events are solely those prompted by the screening examination.
Arm/Group Title	Colorectal Screening
Arm/Group Description	Participants undergo a colorectal examination with a flexible sigmoidoscope at baseline and year 5. Participants complete a Dietary Questionnaire (DQX) at baseline and a Dietary History Questionnaire (DHQ) at study years 3-6. An Annual Study Update (ASU) (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 colorectal cancers and all deaths that occur among both screened and control arm subjects during the trial.
All Cause Mortality
	Colorectal Screening
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Colorectal Screening
	Affected / at Risk (%)	# Events
Total	0/77445 (0%)
Other (Not Including Serious) Adverse Events
	Colorectal Screening
	Affected / at Risk (%)	# Events
Total	504/77445 (0.7%)
General disorders
Anxiety	2/77445 (0%)	2
Bleeding	53/77445 (0.1%)	53
Dizzy	204/77445 (0.3%)	210
Fainted	101/77445 (0.1%)	101
Nausea	101/77445 (0.1%)	101
Pain	41/77445 (0.1%)	42
Perforated Bowel	3/77445 (0%)	3
Other Adverse Event	7/77445 (0%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.