Colorectal Cancer Study

by National Cancer Institute

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, or PLCO, is a large-scale clinical trial to determine whether certain cancer screening tests reduce death from cancer. The PLCO is testing the effectiveness of early prostate, lung, colorectal, and ovarian cancer detection using the following tests: digital rectal examination and blood prostate-specific antigen (PSA) testing for prostate cancer; chest X-ray for lung cancer; flexible sigmoidoscopy for colorectal cancer; and transvaginal ultrasound and the blood cancer antigen, CA-125, for ovarian cancer. Screening for cancer may enable doctors to discover and successfully treat the disease earlier, thus preventing deaths. Numerous epidemiologic and other studies are also part of this research.

Sponsored and run by the National Cancer Institute's (NCI) Division of Cancer Prevention, the PLCO trial is taking place at 10 screening centers across the United States: Birmingham, Ala.; Denver, Colo.;Washington, D.C.; Honolulu, Hawaii; Detroit, Mich.; Minneapolis, Minn.; St. Louis, Mo.; Pittsburgh, Pa.; Salt Lake City, Utah; and Marshfield, Wis.

Between 1993, when the trial opened, and 2001, when enrollment completed, a total of 154,942 women and men between the ages of 55 and 74 joined PLCO. Screening of participants will continue until 2006. Additional follow-up will continue for at least 10 more years to determine the benefits or harms of the cancer screening exams being studied.

The PLCO trial also includes research on the genetic and environmental causes of cancer (prostate, lung, colorectal, ovarian and other types of cancer) and studies of new methods for the early detection of cancer, in collaboration with the NCI's Division of Cancer Epidemiology and Genetics.

Together, prostate, lung, colorectal, and ovarian cancers account for 42 percent of all diagnosed cancers in the United States and nearly half of all cancer deaths (47 percent). An estimated 266,360 people will die of prostate, lung, colorectal and ovarian cancer in this country in 2005.

Background on Colorectal Cancer

Colorectal cancer is the third most commonly diagnosed cancer among both men and women in the United States. Family history of the disease and a personal history of inflammatory bowel disease or polyps are factors known to increase a person's risk of colorectal cancer. A diet high in fat and low in dietary fiber also may increase a person's risk.

The colon and rectum are the lowest portion of the digestive system. The colon is the last five or six feet of the intestine and the rectum is the last eight to ten inches of the colon. Because the areas are connected, cancer researchers often report this as a single type of cancer.

In the PLCO trial, researchers are testing flexible sigmoidoscopy. During a sigmoidoscopy, a thin, lighted viewing instrument is inserted into the rectum to examine the left, or distal, portion of the colorectum. PLCO Subjects with a polyp or mass noted on sigmoidoscopy are often referred for further examination with colonoscopy, a procedure that examines the entire colorectum.

Patient Population, Trial Design, and Data Collection

The PLCO is a randomized, controlled trial in which 154,942 persons ages 55 to 74 at entry are randomly assigned to two study arms: half to undergo cancer screening (intervention group) and half to continue their normal health care routine (control group). Both groups answer yearly questionnaires about their health and give biologic samples (blood and tissue) for studies of cancer causes and of early markers for cancer (biomarkers).

The sigmoidoscopy exam is offered twice--at the initial visit and at either the third or fifth annual visit, depending when the participant enrolled in PLCO. With the completion of enrollment and screening, researchers continue to follow participants in both groups for at least 13 years from the time they enrolled.

Results/Publications

The following PLCO analyses regarding colorectal cancer have been published, with the most recent studies listed first:

Screening and Related Clinical Studies

The PLCO trial offers a unique opportunity to examine the effectiveness of screening flexible sigmoidoscopy in a large, diverse population. Results from the initial screening and 12 months of follow-up were comparable to other studies.

Of 77,465 subjects randomized to the screening arm, 64,658 (83 percent) received the baseline flexible sigmoidoscopy exam. A total of 18 percent of women and 28 percent of men were found to have a positive screen (i.e., a lesion or mass reported). The detection rate of colorectal cancer in subjects undergoing screening was 1.8 per 1,000 in women and 3.8 per 1,000 in men, while the detection rate for advanced adenomas (pre-cancerous polyps) was 23 per 1,000 in women and 43 per 1,000 in men. Because of the large size of the study population, the broad geographic representation, and the follow-up criteria, the results of the PLCO trial will offer a benchmark for screening flexible sigmoidoscopy in the United States.

Repeat screening flexible sigmoidoscopy three years after a negative exam will detect abnormalities or masses in the lower portion of the colon.

The PLCO trial is evaluating the effect of flexible sigmoidoscopy (FSG) on colorectal cancer mortality. The trial screened the intervention group upon entry to the study and then in three years. Individuals included in this analysis had an initial FSG that showed no abnormalities or masses and then underwent a screening FSG three years later.

Of the 11,583 individuals without an abnormality or mass on initial FSG, 9,317 (80.4 percent) returned for repeat screening after three years. Of the people who returned, 1,292 (13.9 percetn) had a polyp or mass detected. Of those with a polyp or mass, 951 (73.6 percent) went on to have follow-up screening, colonoscopy or repeat FSG. In the distal colon, 292 (3.1 percent) were found to have an adenoma (a pre-cancerous polyp) and 78 (0.8 percent) were found to have either an advanced adenoma or cancer.

Data from the second screening for participants in the PLCO trial determined that excellent adherence to repeat screening with flexible sigmoidoscopy could be achieved. However, gender may impact adherence to repeat screening, with women less likely to return for follow-up screening.

This study was comprised of 10,164 patients from the PLCO screening trial who had a negative/normal initial screen. These patients were scheduled for repeat flexible sigmoidoscopy three years after the initial screening. Almost 87 percent of eligible patients returned for repeat screening.

Measures of nonadherence with repeat sigmoidoscopy varied significantly according to gender. Compared with men, women missed the year-three clinic almost two times more often than men, and women who attended the year-three clinic refused repeat sigmoidoscopy more than two times more often than men.

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