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Diagnosis of Cancer

By

Robert Peter Gale

, MD, PhD, Imperial College London

Last full review/revision Jul 2018| Content last modified Aug 2018
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Cancer is suspected based on a person's symptoms, the results of a physical examination, and sometimes the results of screening tests. Occasionally, x-rays obtained for other reasons, such as an injury, show abnormalities that might be cancer. Confirmation that cancer is present requires other tests (termed diagnostic tests).

After cancer is diagnosed, it is staged. Staging is a way of describing how advanced the cancer has become, including such criteria as how big it is and whether it has spread to neighboring tissues or more distantly to lymph nodes or other organs.

Screening for Cancer

Screening tests are used to detect the possibility that a disease is present before symptoms occur. Screening tests usually are not definitive. Results are confirmed or disproved with further examinations and tests. Diagnostic tests are done once a doctor suspects that a person has cancer.

Although screening tests can help save lives, they can be costly and sometimes have psychologic or physical repercussions. Screening test results can be falsely positive or falsely negative:

  • False-positive results: Results that suggest a cancer is present when it actually is not

  • False-negative results: Results that show no hint of a cancer that is actually present

False-positive results can create undue psychologic stress and can lead to other tests that are expensive and risky. False-negative results can lull people into a false sense of security. For these reasons, there are only a small number of screening tests that are considered reliable enough for doctors to use routinely.

Doctors determine whether a particular person is at special risk of cancer—because of age, sex, family history, previous history, or lifestyle—before they choose to do screening tests. The American Cancer Society has provided cancer screening guidelines that are widely used. Other groups have also developed screening guidelines. Sometimes recommendations vary among different groups, depending on how the groups' experts weigh the relative strength and importance of available scientific evidence.

Some screening is carried out as part of routine physical examinations. Doctors may feel the thyroid gland or lymph nodes to detect growths. Dentists examine the mouth and tongue to look for signs of mouth cancers.

In women, two of the most widely used screening tests are the Papanicolaou (Pap) test to detect cervical cancer and mammography to detect breast cancer. Both screening tests have been successful in reducing the death rates from these cancers in certain age groups.

In men, prostate-specific antigen (PSA) levels in the blood may be used to screen for prostate cancer. PSA levels are often high in men with prostate cancer, but levels also are elevated in men with noncancerous (benign) enlargement of the prostate. As such, the main drawback to its use as a screening test is the large number of false-positive results, which generally lead to more invasive tests such as a prostate biopsy. And doctors are now realizing that not all prostate cancers found on biopsy will go on to cause problems. Whether the PSA test should be used routinely to screen for prostate cancer is unresolved, with varying recommendations from different groups. Men over 50 should discuss the PSA test with their doctor.

A common screening test for colon cancer involves checking the stool for blood that cannot be seen by the naked eye (occult blood). Finding occult blood in the stool is an indication that something is wrong somewhere in the digestive tract. The problem may be cancer, although many other disorders, such as ulcers, hemorrhoids, diverticulosis (small pouches in the colon wall), and abnormal blood vessels in the intestinal walls, can also cause small amounts of blood to leak into the stool. In addition, taking an aspirin or another nonsteroidal anti-inflammatory drug (NSAID) or even eating red meat can temporarily cause a positive test result. Positive results on some older tests can occasionally be caused by consuming certain raw fruits and vegetables (turnips, cauliflower, broccoli, melons, radishes, and parsnips). Newer screening tests for occult blood use a different technique and are much less susceptible to such errors. Outpatient procedures such as sigmoidoscopy, colonoscopy, and a special type of computed tomography (CT) of the colon (CT colonography) are also often used for colon cancer screening.

Routine self-examination for signs of cancer has sometimes been recommended. However, except possibly for testicular cancer, home screening with self-examinations has not been proved to be effective in identifying cancer, so even if people do examinations at home it is important to also follow recommendations for screening tests.

Some screening tests can be done at home, such as checking the stool for blood by putting a small amount of stool on a special card and mailing it to a laboratory to be processed. An abnormal result should prompt a visit to the doctor for confirmation.

Tumor markers are substances secreted into the bloodstream by certain tumors. It was first thought that measuring levels of these markers would be an excellent way to screen asymptomatic people for cancer. However, tumor markers are often present to some extent in the blood of people who do not have cancer. Finding a tumor marker does not necessarily mean a person has cancer, and tumor markers have a very limited role in cancer screening.

Table
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Cancer Screening Recommendations*

Procedure

Frequency

Skin cancer

Physical examination

Should be part of a routine checkup

Special screening examinations or tests (such as whole body photography) not recommended

Lung cancer

Low-dose helical (spiral) computed tomography

Not recommended as part of routine evaluations

Yearly in people who smoke or who quit smoking less than 15 years ago who are between ages 55 and 74

Rectal and colon cancer

Stool examination for occult blood, immunohistochemical test, or stool DNA test

Yearly after age 50†

Sigmoidoscopic or colonoscopic examination

Every 5 years beginning at age 50 (sigmoidoscopy)

Every 10 years beginning at age 50 (colonoscopy)

Computed tomography colonography

Every 5 years, starting at age 50

Prostate cancer

Blood test for prostate-specific antigen

The benefit of screening is uncertain, so men over 50 and their doctors should discuss the possible risks and benefits of screening

African American men and men whose father or brother developed prostate cancer before age 65 should have this discussion at age 45

Cervical cancer

Papanicolaou (Pap) test and human papillomavirus (HPV) DNA test

Pap test every 3 years between ages 21 and 29

Pap test plus HPV DNA test every 5 years between ages 30 and 65 or Pap test every 3 years

No testing after age 65 if previous test results were normal and most recent test was within 5 years

Breast cancer

Mammography‡

Women ages 40–44: Option to start annual screening

Women ages 45–54: Yearly

Women ≥ 55: Every 2 years; screening continues as long as woman is in good health and expected to live at least 10 more years

* Recommendations for screening are influenced by many factors. These screening recommendations, based primarily on those of the American Cancer Society, are for asymptomatic people with an average risk of cancer. For people with a higher risk, such as those with a strong family history of certain cancers or those who have had a previous cancer, screening may be recommended more frequently or to start at a younger age. Screening tests other than those listed here may also be recommended. Furthermore, other organizations, such as the U.S. Preventive Services Task Force, may have slightly different recommendations. A person's physician can help the person decide when to begin screening and which tests should be used.

† Some experts recommend starting screening at age 45 years because of an increasing rate of colon and rectal cancer in people under 50.

‡ Magnetic resonance imaging (MRI) is recommended yearly, in addition to mammography, starting at age 30 for some women at high risk of breast cancer.

Diagnosis of Cancer

Usually, when a doctor first suspects cancer, some type of imaging study, such as x-rays, ultrasonography, or computed tomography (CT), is done. For example, a person with chronic cough and weight loss might have a chest x-ray. A person with recurrent headaches and trouble seeing might have brain CT or magnetic resonance imaging (MRI). Although these tests can show the presence, location, and size of an abnormal mass, they cannot confirm that cancer is the cause.

Biopsy

Cancer is confirmed by obtaining a piece of the tumor through needle biopsy or surgery and finding cancer cells on microscopic examination of samples from the suspected area. Usually, the sample must be a piece of tissue, although sometimes examination of the blood is adequate (such as in leukemia). Obtaining a tissue sample is termed a biopsy.

Biopsies can be done by cutting out a small piece of tissue with a scalpel, but very commonly the sample is obtained using a hollow needle. Such tests are commonly done without the need for an overnight hospital stay (outpatient procedure). Doctors often use ultrasonography or CT to guide the needle to the right location. Because biopsies can be painful, the person is usually given a local anesthetic to numb the area.

Tumor markers

When examination findings or imaging test results suggest cancer, measuring blood levels of tumor markers (substances secreted into the bloodstream by certain tumors) may provide additional evidence for or against the diagnosis of cancer. In people who have been diagnosed with certain types of cancer, tumor markers may be useful to monitor the effectiveness of treatment and to detect possible recurrence of the cancer. For some cancers, the level of a tumor marker drops after treatment and increases if the cancer recurs.

Some tumor markers cannot be measured in the blood but instead can be found on tumor cells. These markers are found by examining tissue from a biopsy sample. HER2 and EGFR are examples of tumor markers found on tumor cells.

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Some Tumor Markers*

Tumor Marker

Description

Comment About Testing

Alpha-fetoprotein (AFP)

Elevated AFP levels often are found in the blood of people with liver cancer (hepatocellular carcinoma). In addition, elevated AFP is often found in people with certain cancers of the ovary or testis.

Testing can be useful in monitoring treatment and perhaps for diagnosis of cancer in a person with cirrhosis (liver damage due to alcohol or viral hepatitis).

Beta-human chorionic gonadotropin (ß-HCG)

This hormone is produced during pregnancy but also occurs in women who have a cancer originating in the placenta and in men with testicular cancer.

Testing can be useful in diagnosing such cancers and in monitoring treatment.

Beta22)-microglobulin

Levels may be elevated in people with multiple myeloma and some lymphomas.

This test is not recommended for cancer screening.

Calcitonin

Calcitonin is produced by certain cells in the thyroid gland (C cells). Blood levels are elevated in medullary thyroid cancer.

This test may be used to detect the presence of cancer and monitor response to treatment of medullary thyroid cancer.

Carbohydrate antigen 125 (CA-125)

Levels may be elevated in women with a variety of gynecologic diseases, including ovarian cancer.

This test is not recommended for cancer screening.

Carbohydrate antigen 19-9 (CA 19-9)

Levels may be elevated in people with cancers of the digestive tract, particularly pancreatic cancer.

This test is used in monitoring response to treatment and in the diagnosis of tumors of unknown origin.

Carbohydrate antigen 27.29 (CA27.29)

Levels may be elevated in people with breast cancer.

This test can be used in monitoring treatment.

Carcinoembryonic antigen (CEA)

Levels may be elevated in the blood of people with cancer of the colon. Blood levels may also be elevated in patients with other cancers or noncancerous inflammatory conditions.

After surgery for colon cancer, testing can be useful in monitoring treatment and detecting recurrence.

Prostate-specific antigen (PSA)

Levels are elevated in men with noncancerous (benign) enlargement of the prostate and often are considerably higher in men with prostate cancer. Men with an elevated PSA level should be evaluated further by a doctor.

Testing may be useful in screening for cancer and is helpful in detecting recurrence after treatment.

Thyroglobulin

Levels may be elevated in people with thyroid cancer or benign thyroid conditions.

This test is not recommended for routine screening but may be helpful for monitoring response to treatment of thyroid cancer.

*Because tumor markers can also be produced by noncancerous tissue, doctors generally do not use them to screen healthy people. Exceptions may include PSA for prostate cancer and AFP for people at risk of hepatoma. In families with inherited medullary thyroid cancer, a rare condition, levels of calcitonin in the blood also may be a useful screening test.

Staging Cancer

When cancer is diagnosed, staging tests help determine how extensive the cancer is in terms of its location, size, growth into nearby structures, and spread to other parts of the body. People with cancer sometimes become impatient and anxious during staging tests, wishing for a prompt start of treatment. However, staging allows doctors to determine the most appropriate treatment as well as help to determine prognosis.

Staging may use scans or other imaging tests, such as x-ray, CT, MRI, bone scans with radioactive materials, or positron emission tomography (PET). The choice of staging test(s) depends on the type of cancer. CT is used to detect cancer in many parts of the body, including the brain and lungs and parts of the abdomen, including the adrenal glands, lymph nodes, liver, and spleen. MRI is of particular value in detecting cancers of the brain, bones, and spinal cord.

Biopsies are often needed to confirm the presence of tumor for staging purposes and can sometimes be done together with the initial surgical treatment of a cancer. For example, during a laparotomy (an abdominal operation) to remove colon cancer, a surgeon removes nearby lymph nodes to check for spread of the cancer. During surgery for breast cancer, the surgeon biopsies or removes a lymph node located in the armpit (the first lymph nodes to which cancer is likely to spread, also called a sentinel lymph node) to determine whether the breast cancer has spread there. Evidence of spread, along with features of the primary tumor, helps the doctor determine whether further treatment is needed.

When staging is based only on initial biopsy results, physical examination, and imaging, the stage is referred to as clinical. When the doctor uses results of a surgical procedure or additional biopsies, the stage is referred to as pathologic or surgical. The clinical and pathologic (surgical) stages may differ.

In addition to imaging tests, doctors often obtain blood tests to see if the cancer has begun to affect the liver, bones, or kidneys.

Grading Cancer

Grading is a measure of how quickly the cancer is growing or spreading (called aggressiveness). A cancer's grade can help doctors determine prognosis. Grade is determined by examining the tissue specimen obtained during a biopsy. Grade is based on the degree of abnormality of the appearance of cancer cells on microscopic examination. More abnormal appearing cells are more aggressive. For many cancers, grading scales have been developed.

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