Cancer Screening Overview (PDQ®)–Health Professional Version

Cancer Screening

Purpose of Summary

The purpose of this summary is to present an explicit evidence-based approach used in the development of the screening summaries. In reaching conclusions, evidence on the balance of risks and benefits is weighed. Cost and cost-effectiveness, however, is not taken into account. Assignment of levels of evidence associated with such screening tests is also discussed.

Potential Benefits and Harms

In general, the benefit of cancer screening derives from detecting cancer in earlier and more treatable stages, and thereby, reducing mortality from cancer. In addition, for some cancer types and screening modalities, such as endoscopic screening for colorectal cancer and Papanicolaou (Pap) smears for cervical cancer, screening can also prevent the occurrence of cancer by identifying and removing cancer precursors. Screening may also reduce cancer morbidity when the treatment for earlier-stage cancer is associated with fewer side effects than the treatment for advanced cancers.

There are documented harms from screening as follows:[1]

The possibility of serious test-related complications, which may be immediate (e.g., perforation with colonoscopy) or delayed (e.g., potential carcinogenesis from radiation exposure).
A false-positive screening test result, which may cause anxiety and lead to additional invasive diagnostic procedures.
Overdiagnosis, which occurs when screening procedures detect cancers that would never become clinically apparent in the absence of screening.

Because screening tests themselves are generally noninvasive, immediate harms from the screen itself are typically minor. Colonoscopy is an exception in that it is an invasive test that also functions as a diagnostic follow-up examination for other colorectal cancer screening modalities, such as a fecal occult blood (FOB) test.

Commonly used screening tests, such as mammography for breast cancer or prostate-specific antigen (PSA) for prostate cancer, have false-positive rates per screen in the range of 5% to 10%; with repeat screening, cumulative false-positive rates for these tests are substantially higher.[2-4] Follow-up invasive diagnostic procedures, such as a prostate biopsy, are associated with low but non-negligible risks of complications. For screening tests such as colonoscopy or Pap smears where precursor lesions, in addition to invasive cancer, are targets of the screen, the definition of a false positive is modified from simply a positive screen in an individual without cancer. For example, for cervical cancer screening, a positive Pap smear with an eventual diagnosis of high-grade intraepithelial lesion (HSIL) would not be considered a false positive, since HSIL is a target lesion.

Overdiagnosis occurs when screening procedures detect cancers that would never become clinically apparent in the absence of screening. It is a special concern because identification of the cancer does not benefit the individual, while the side effects of diagnostic procedures and cancer treatment may cause significant harm. The overall harm of overdiagnosis is related to both the frequency of its occurrence, as well as to the downstream consequences of subsequent treatment. For example, in prostate cancer screening with PSA, there is a high rate of overdiagnosed disease and the harms of curative treatment, including impotence and urinary incontinence, are relatively common, serious, and long-lasting. Therefore, overdiagnosis is a major source of harms in PSA screening.[5] Some of the harms of overdiagnosis may be mitigated by strategies, such as active surveillance in prostate cancer, that attempt to defer immediate treatment in favor of following patients for any signs of worsening prognosis.

In general, overdiagnosis is more common in older individuals and those with otherwise limited life expectancy since the slowly growing lesions associated with overdiagnosed cancers have less time to become clinically apparent in such persons. Therefore, attempts have been made to discourage screening beyond certain age ranges; for example, most recommendations for mammography screening exclude women aged 75 or older or those with less than 10 years of life expectancy.[6]

In developing the cancer screening summaries, the PDQ Screening and Prevention Editorial Board uses the following definitions:

Screening is a means of detecting disease early in asymptomatic people.
Positive results of examinations, tests, or procedures are not usually diagnostic but identify persons who warrant further evaluation.
Following a positive screening test, additional procedures may rule out cancer or lead to a biopsy yielding tissue to confirm the diagnosis of cancer.

The PDQ does not issue clinical practice guidelines. Many public health organizations present guidelines for health care and screening activities whose quality varies widely. Some rely on systematic review of evidence of variable quality, and some are potentially influenced by the professional, financial, and intellectual interests of guideline authors and funders that may conflict with the primary interest—the overall well-being of the patient.[7-9]

The highest quality guidelines as assessed by the Appraisal of Guidelines for Research and Evaluation (AGREE) are those based on the best systematic reviews as evaluated by the Assessment of Multiple Systematic Reviews (AMSTAR).