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 (TVU) and the blood cancer antigen (CA)-125 for ovarian cancer. Screening for cancer may enable doctors to discover and successfully treat the disease earlier, preventing deaths. Numerous epidemiologic and other studies are also part of the research.

Sponsored and run by the National Cancer Institute's Division of Cancer Prevention, the PLCO trial is taking place at 10 screening centers across the country: 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 was completed, 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 (PLCO and other types of cancer) and studies of new methods for the early detection of cancer, in collaboration with the National Cancer Institute'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 2005.

Background on Ovarian Cancer:

In 2005 in the United States, it is estimated that ovarian cancer will be diagnosed in 22,220 women and result in 16,200 deaths. Ovarian cancer is the fourth leading cause of cancer death in women. Although ovarian cancer accounts for about 4 percent of all cancers in women, it has the highest mortality of all gynecologic cancers because it is often diagnosed at an advanced stage. This is due to a lack of early symptoms and proven screening tests. Long-term survival is achieved in less than a third of patients.

Current screening tests include bimanual palpation, CA-125, and TVU. Feeling the ovaries during a pelvic exam is a widely used technique but it is not sensitive enough to detect early-stage cancer. CA-125 is a test that measures the level of cancer antigen 125, a sugar protein in the blood. Often this protein is released when cells are inflamed or damaged. Increased levels of CA-125 can be a sign of cancer. TVU is a procedure that uses sound waves to examine the vagina, uterus, fallopian tubes, ovaries, and bladder for abnormalities.

Patient Population, Trial Design, and Data Collection in the PLCO:

The PLCO is a randomized, controlled trial in which over 150,000 people 55 to 74 years old at entry were randomized 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. The first ovarian cancer screening tests were performed on the first participant on November 15, 1993.

The 39,115 women in the intervention arm are screened for ovarian cancer using CA-125 annually six times and TVU annually four times. Originally, feeling the ovaries during a physical exam was included in the protocol, but the procedure was dropped in 1998 after review of the data revealed that no ovarian cancers had been detected with this procedure alone. The primary objective of the ovarian component of the PLCO trial is to determine in women, age 55 to 74 years old at entry, whether screening with CA-125 and TVU can decrease mortality from ovarian cancer.

If a participant has a positive result from a screening test, the results are shared with the participant and her physician or a referral to an appropriate physician is made. The PLCO trial design does not dictate the type of follow-up a person should have, although information on follow-up tests is collected. Participants in the intervention and control groups will be followed for at least 13 years from the time they enter the study.

Results/Publications:

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

Screening and Related Clinical Studies

• In the first year of screening in the PLCO Trial, CA-125 and TVU were able to identify both early- and late-stage ovarian cancers, but the ability of these tests to accurately predict the presence of the disease was relatively low. The effect that screening for ovarian cancer has on mortality in the PLCO population is still unclear and will require longer follow-up.

This paper summarizes initial data gathered from baseline screenings, the initial tests performed when patients were first enrolled in the trial. Of the 28,816 women screened, 29 tumors were detected. Twenty of these tumors were invasive, and nine were tumors of low malignant potential. The tumors were identified among 1,338 women who had an abnormal TVU and 402 women who had an abnormal CA-125 test.

The positive predictive value of these tests for invasive cancer was 3.7 percent for an abnormal CA-125 test, 1 percent for an abnormal TVU, and 23.5 percent if both tests were abnormal. The authors recommend that no changes be made to the current ovarian cancer screening guidelines of the US Preventive Services Task Force. These guidelines, from 1996, state that "routine screening for ovarian cancer by ultrasound, the measurement of serum tumor markers, or pelvic examination is not recommended." Since this recommendation is based on data from only the first year of data from the trial, future follow-up will offer more information on the effectiveness of these screening tests to prevent mortality from ovarian cancer.

Reference: Buys SS, Partridge E, et al. "Ovarian Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: Findings from the Initial Screen of a Randomized Trial." American Journal of Obstetrics and Gynecology, November 15, 2005.

Studies of Cancer Causes

• In postmenopausal women, complex ovarian cysts, which have multiple compartments, do not appear to be the immediate precursors of ovarian cancer. Also, these cysts are not associated with other ovarian cancer risk factors, such as family history of ovarian or breast cancers.

Precursors to ovarian cancer have yet to be identified, but possible candidates are non-malignant ovarian abnormalities like cysts that are detected by TVU in symptom-free postmenopausal women. If these abnormalities were cancer precursors, they would be found more often in women with established risk factors for ovarian cancer.

Researchers compared TVU findings from 20,000 postmenopausal women and compiled data on their risk factors from participant questionnaires filled out when the women were enrolled in the PLCO study. Researchers found that complex ovarian cysts were less prevalent in women who had more children but were unrelated to oral contraceptive use, both strong ovarian cancer protective factors. Prevalence of cysts was unrelated to a woman's age or family cancer history, both strong risk factors for ovarian cancer. This study suggests that complex ovarian cysts are not precursors of ovarian cancer in postmenopausal women.

Reference: Hartge P, Hayes R, et al. "Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors." American Journal of Obstetrics and Gynecology. 183(5):1232-1237. November 2000.

# # #

• Ovarian Cancer Home Page ¹
  (http://www.cancer.gov/cancertopics/types/ovarian)
• Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Web Page ²
  (http://dcp.cancer.gov/programs-resources/groups/ed/programs/plco)
• Screening and Testing to Detect Cancer Home Page ³
  (http://www.cancer.gov/cancertopics/screening)
• What You Need To Know About™ Ovarian Cancer ⁴
  (http://www.cancer.gov/cancertopics/wyntk/ovary)

How can we help?

We offer comprehensive research-based information for patients and their families, health professionals, cancer researchers, advocates, and the public.

• Call NCI’s Cancer Information Service at 1–800–4–CANCER (1–800–422–6237)
• Visit us at http://www.cancer.gov or http://www.cancer.gov/espanol
• Chat using LiveHelp, NCI’s instant messaging service, at http://www.cancer.gov/livehelp
• E-mail us at cancergovstaff@mail.nih.gov
• Order publications at http://www.cancer.gov/publications or by calling 1–800–4–CANCER
• Get help with quitting smoking at 1–877–44U–QUIT (1–877–448–7848)

Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

Any substance that causes the body to make a specific immune response.

An initial measurement that is taken at an early time point to represent a beginning condition, and is used for comparison over time to look for changes. For example, the size of a tumor will be measured before treatment (baseline) and then afterwards to see if the treatment had an effect.

The organ that stores urine.

A substance that may be found in high amounts in the blood of patients with certain types of cancer, including ovarian cancer. CA-125 levels may also help monitor how well cancer treatments are working or if cancer has come back. Also called cancer antigen 125.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

A substance that may be found in high amounts in the blood of patients with certain types of cancer, including ovarian cancer. Cancer antigen 125 levels may also help monitor how well cancer treatments are working or if cancer has come back. Also called CA-125.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

Having to do with the colon or the rectum.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A sac or capsule in the body. It may be filled with fluid or other material.

The process of identifying a disease, such as cancer, from its signs and symptoms.

An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. Also called DRE.

A term used to describe cancer that is early in its growth, and may not have spread to other parts of the body. What is called early stage may differ between cancer types.

The study of the patterns, causes, and control of disease in groups of people.

A slender tube through which eggs pass from an ovary to the uterus. In the female reproductive tract, there is one ovary and one fallopian tube on each side of the uterus.

A record of the relationships among family members along with their medical histories. This includes current and past illnesses. A family history may show a pattern of certain diseases in a family. Also called family medical history.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Having to do with the female reproductive tract (including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina).

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

The group receiving the study agent that is being tested in a clinical trial or clinical study.

Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

The state of being mortal (destined to die). Mortality also refers to the death rate, or the number of deaths in a certain group of people in a certain period of time. Mortality may be reported for people who have a certain disease, live in one area of the country, or who are of a certain gender, age, or ethnic group.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

Examination by pressing on the surface of the body to feel the organs or tissues underneath.

Having to do with the pelvis (the lower part of the abdomen located between the hip bones).

A physical examination in which the health care professional will feel for lumps or changes in the shape of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The health care professional will also use a speculum to open the vagina to look at the cervix and take samples for a Pap test. Also called internal examination.

An exam of the body to check for general signs of disease.

Medical doctor.

Having to do with the time after menopause. Menopause (“change of life”) is the time in a woman's life when menstrual periods stop permanently.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

A protein made by the prostate gland and found in the blood. Prostate-specific antigen blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland. Also called PSA.

Something that may decrease the chance of getting a certain disease. Some examples of protective factors for cancer are getting regular physical activity, staying at a healthy weight, and having a healthy diet.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A detailed plan of a scientific or medical experiment, treatment, or procedure. In clinical trials, it states what the study will do, how it will be done, and why it is being done. It explains how many people will be in the study, who is eligible to take part in it, what study drugs or other interventions will be given, what tests will be done and how often, and what information will be collected.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

In medicine, the act of a doctor in which a patient is sent to another doctor for additional healthcare services.

Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.

Examination of the lower colon using a sigmoidoscope, inserted into the rectum. A sigmoidoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. Also called proctosigmoidoscopy.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

A procedure used to examine the vagina, uterus, fallopian tubes, ovaries, and bladder. An instrument is inserted into the vagina that causes sound waves to bounce off organs inside the pelvis. These sound waves create echoes that are sent to a computer, which creates a picture called a sonogram. Also called transvaginal sonography and TVS.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).

A procedure in which high-energy sound waves are bounced off internal tissues or organs and make echoes. The echo patterns are shown on the screen of an ultrasound machine, forming a picture of body tissues called a sonogram. Also called ultrasonography.

The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called womb.

The muscular canal extending from the uterus to the exterior of the body. Also called birth canal.