Cancer screening

A patient preparing for breast cancer screening by mammography

Cancer screening aims to detect cancer before symptoms appear.^[1] This may involve blood tests, urine tests, other tests, or medical imaging.^[1] The benefits of screening in terms of cancer prevention, early detection and subsequent treatment must be weighed against any harms.

Universal screening, mass screening or population screening involves screening everyone, usually within a specific age group.^[2] Selective screening identifies people who are known to be at higher risk of developing cancer, such as people with a family history of cancer.^[2]

Screening can lead to false positive results and subsequent invasive procedures.^[3] Screening can also lead to false negative results, where an existing cancer is missed. Controversy arises when it is not clear if the benefits of screening outweigh the risks of the screening procedure itself, and any follow-up diagnostic tests and treatments.

Screening tests must be effective, safe, well-tolerated with acceptably low rates of false positive and false negative results. If signs of cancer are detected, more definitive and invasive follow-up tests are performed to reach a diagnosis. Screening for cancer can lead to cancer prevention and earlier diagnosis. Early diagnosis may lead to higher rates of successful treatment and extended life. However, it may also falsely appear to increase the time to death through lead time bias or length time bias.

Risks and benefits

Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives.^[4] Screening can lead to substantial false positive result and subsequent invasive procedures.^[3] The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. Cancer screening is not indicated unless life expectancy is greater than five years and the benefit is uncertain over the age of 70.^[5]

Breast cancer

There is general agreement in the scientific community that breast screening reduces mortality from the disease.^[6] There is some controversy however about the number of lives saved by breast screening and the number of cancers diagnosed and treated that would not have caused any health problems in the participants' lifetime, sometimes known as over-diagnosis and over-treatment.^[7][8] Non-invasive breast cancers, or ductal carcinoma in situ, sometimes progress to invasive cancer but sometimes do not. Since doctors cannot usually distinguish which DCIS will go on to invasive cancer, most are treated. This is where over-treatment can arise.

Recommendations to attend to mammography screening vary across countries and organizations, with the most common difference being the age at which screening should begin, and how frequently or if it should be performed, among women at typical risk for developing breast cancer.^[9] For example, in England, all women were invited for screening once every three years beginning at age 50,^[10] though this is transitioning to a start at age 47 by 2016.^[11] Some other organizations recommend mammograms begin as early as age 40 in normal-risk women, and take place more frequently, up to once each year. Women at higher risk may benefit from earlier or more frequent screening. Women with one or more first-degree relatives (mother, sister, daughter) with premenopausal breast cancer often begin screening at an earlier age, perhaps at an age 10 years younger than the age when the relative was diagnosed with breast cancer.

The U.S. Preventative Services Task Force (USPSTF) recommends population screening mammography once for every two years for all women aged 50–74, with decisions about screening younger and older women being determined by consideration of the individual's risk factors and the benefits and harms of screening. They do not recommend either breast self-examination or clinical breast examination.^[12] Their recommendation is similar to the World Health Organization's, and less aggressive than some American organizations. A 2011 Cochrane review came to slightly different conclusions with respect to breast cancer screening stating that routine mammography may do more harm than good.^[6]

As the debate about the benefits and harms of mammography screening escalated in the United Kingdom, the National Clinical Director for Cancer and the Executive Director of Cancer Research UK commissioned a panel of whom the members had not previously published on breast screening to review the evidence. Members were experts in medical statistics, epidemiology, oncology and a patient representative. This independent review was published in the Lancet on October 30, 2012.^[13] The main conclusion of the independent panel was that screening reduced breast cancer mortality, although overdiagnosis also occurs.

Cervical cancer

Microscope image of the cervical gland showing an area of high grade epithelial dysplasia.

Cervical screening by the Pap test or other methods is highly effective at detecting and preventing cervical cancer, although there is a serious risk of overtreatment in young women up to the age of 20 or beyond, who are prone to have many abnormal cells which clear up naturally.^[14] There is a considerable range in the recommended age at which to begin screening around the world. According to the 2010 European guidelines for cervical cancer screening, the age at which to commence screening ranges between 20–30 years of age, "but preferentially not before age 25 or 30 years", depending on the burden of the disease in the population and the available resources.^[15]

In the United States the rate of cervical cancer is 0.1% among women under 20 years of age, so the American Cancer Society as well as the American College of Obstetricians and Gynecologists strongly recommend that screening begin at age 21, regardless of age at sexual initiation or other risk-related behaviors.^[16][17][18] For healthy women aged 21–29 who have never had an abnormal Pap smear, cervical cancer screening with cervical cytology (Pap smear) should occur every 3 years, regardless of HPV vaccination status.^[19] The preferred screening for women aged 30–65 is "co-testing", which includes a combination of cervical cytology screening and HPV testing, every 5 years.^[19] However, it is acceptable to screen this age group with a Pap smear alone every 3 years.^[19] In women over the age of 65, screening for cervical cancer may be discontinued in the absence of abnormal screening results within the prior 10 years and no history of CIN 2 or higher.^[19]

Bowel cancer

A bowel polyp that can be identified by sigmoidoscopy. Some polyps will develop into cancers if not removed.

Screening for colorectal cancer, if done early enough, is preventive because almost all^[20][21] colorectal cancers originate from benign growths called polyps, which can be located and removed during a colonoscopy (see colonic polypectomy).

The US Preventive Services Task Force recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy, in adults, beginning at age 50 years and continuing until age 75 years.^[22] For people over 75 or those with a life expectancy of less than 10 years screening is not recommended. A new enzyme method for colorectal cancer screening is the M2-PK Test,^[23] which is able to detect bleeding and non-bleeding colorectal cancers and polyps.^[22] In 2008, Kaiser Permanente Colorado implemented a program that used automated calls and sends fecal immunochemical test kits to patients who are overdue for colorectal cancer screenings. The program has increased the proportion of all eligible members screened by 25 percent.^[24] DNA testing with Cologuard test has been FDA-approved.^[25]

In England, adults are screened biennially via faecal occult blood testing between the ages of 60 and 74 years.^[26]

Prostate cancer

When screening for prostate cancer, the PSA test may detect small cancers that would never become life-threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation. Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse).^[27] The U.S. Preventative Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA) based screening for prostate cancer finding, "there is a very small potential benefit and significant potential harms" and concluding, "while everyone wants to help prevent deaths from prostate cancer, current methods of PSA screening and treatment of screen-detected cancer are not the answer."^[28][29] Most North American medical groups recommend individualized decisions about screening, taking into consideration the risks, benefits, and the patients' personal preferences.^[30]

Lung Cancer

Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances.^[31] In the 2010s recommendations by medical authorities are turning in favour of lung cancer screening, which is likely to become more widely available in the advanced economies.

In December 2013 the U.S. Preventative Services Task Force (USPSTF) changed its long-standing recommendation that there is insufficient evidence to recommend for or against screening for lung cancer to the following: "The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults ages 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery".^[32]

Pancreatic cancer

It is generally agreed that general screening of large groups for pancreatic cancer is not at present likely to be effective, and outside clinical trials there are no programmes for this. The European Society for Medical Oncology recommends regular screening with endoscopic ultrasound and MRI/CT imaging for those at high risk from inherited genetics,^[33] in line with other recommendations,^[34][35] which may also include CT.^[34][36]

Other cancers

There is insufficient evidence to recommend for or against screening for skin cancer,^[37] oral cancer^[38] and bladder cancer.^[39] Routine screening is not recommended for testicular cancer,^[40] and ovarian cancer.^[41]

Determining if a screening is useful

Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.^[1] These factors include:

• Possible harms from the screening test: Some types of screening tests, such as X-ray images, expose the body to potentially harmful ionizing radiation. There is a small chance that the radiation in the test could cause a new cancer in a healthy person. Screening mammography, used to detect breast cancer, is not recommended to men or to young women because they are more likely to be harmed by the test than to benefit from it. Other tests, such as a skin check for skin cancer, have no significant risk of harm to the patient. A test that has high potential harms is only recommended when the benefits are also high.
• The likelihood of the test correctly identifying cancer: If the test is not sensitive, then it may miss cancers. If the test is not specific, then it may wrongly indicate cancer in a healthy person. All cancer screening tests produce both false positives and false negatives, and most produce more false positives. Experts consider the rate of errors when making recommendations about which test, if any, to use. A test may work better in some populations than others. The positive predictive value is a calculation of the likelihood that a positive test result actually represents cancer in a given individual, based on the results of people with similar risk factors.
• The likelihood of cancer being present: Screening is not normally useful for rare cancers. It is rarely done for young people, since cancer is largely a disease found in people over the age of 50. Countries often focus their screening recommendations on the major forms of treatable cancer found in their population. For example, the United States recommends universal screening for colon cancer, which is common in the US, but not for stomach cancer, which is less common; by contrast, Japan recommends screening for stomach cancer, but not colon cancer, which is rarer in Japan. Screening recommendations depend on the individual's risk, with high-risk people receiving earlier and more frequent screening than low-risk people.
• Possible harms from follow-up procedures: If the screening test is positive, further diagnostic testing is normally done, such as a biopsy of the tissue. If the test produces many false positives, then many people will undergo needless medical procedures, some of which may be dangerous.
• Whether suitable treatment is available and appropriate: Screening is discouraged if no effective treatment is available.^[2] When effective and suitable treatment is not available, then diagnosis of a fatal disease produces significant mental and emotional harms. For example, routine screening for cancer is typically not appropriate in a very frail elderly person, because the treatment for any cancer that is detected might kill the patient.
• Whether early detection improves treatment outcomes: Even when treatment is available, sometimes early detection does not improve the outcome. If the treatment result is the same as if the screening had not been done, then the only screening program does is increase the length of time the person lived with the knowledge that he had cancer. This phenomenon is called lead-time bias. A useful screening program reduces the number of years of potential life lost (longer lives) and disability-adjusted life years lost (longer healthy lives).
• Whether the cancer will ever need treatment: Diagnosis of a cancer in a person who will never be harmed by the cancer is called overdiagnosis. Overdiagnosis is most common among older people with slow-growing cancers. Concerns about overdiagnosis are common for breast and prostate cancer.
• Whether the test is acceptable to the patients:If a screening test is too burdensome, such as requiring too much time, too much pain, or culturally unacceptable behaviors, then people will refuse to participate.^[2]
• Cost of the test: Some expert bodies, such as the U.S. Preventative Services Task Force, completely ignore the question of money. Most, however, include a cost-effectiveness analysis that, all else being equal, favors less expensive tests over more expensive tests, and attempt to balance the cost of the screening program against the benefits of using those funds for other health programs. These analyses usually include the total cost of the screening program to the healthcare system, such as ordering the test, performing the test, reporting the results, and biopsies for suspicious results, but not usually the costs to the individual, such as for time taken away from employment.
• The extent to which a cancer is treatable: if a person has a low life expectancy or otherwise is in the end stages of a chronic condition, then such a patient may have a better life by ignoring the cancer even if one were found. If the diagnosis of cancer would not result in a change in care then cancer screening would not likely result in a positive outcome. Overdiagnosis in this case occurs, for example, in patients with end-stage renal disease and organizations recommend against cancer screening for such patients.^[42][43]

Whole body imaging

Full body CT scans are available for cancer screening, but this type of medical imaging to search for cancer in people without clear symptoms can create problems such as increased exposure to ionizing radiation. However, magnetic resonance imaging (MRI) scans are not associated with a radiation risk, and MRI scans are now being evaluated for their use in cancer screening.^[44] Researchers at the University College London are developing an MRI cancer screening technique called glucose chemical exchange saturation transfer (glucoCEST) which may be to detect cancerous tumors in more detail than a traditional PET/CT scan without the radiation exposure associated with a PET/CT scan. The technique is based on cancerous tumours consumption of glucose at up to 200 times the rate of normal cells and involves having a patient consume a sugary/glucose heavy food and then using a traditional MRI focused on glucose uptake within the body to detect cancerous tumours. Animal studies of glucoCEST have shown promise.^[45]

There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations.

References

Further reading

• Smith, RA; Cokkinides, V; Eyre, HJ (2007). "Cancer screening in the United States, 2007: A review of current guidelines, practices, and prospects". CA: A Cancer Journal for Clinicians 57 (2): 90–104. doi:10.3322/canjclin.57.2.90. PMID 17392386. 
• Aziz, Khalid; Wu, George Y., eds. (2002). Cancer Screening: A Practical Guide for Physicians. Current Clinical Practice. Humana Press. ISBN 9780896038653. 

External links

• NHS cancer screening programmes
• Screening for cancer, Cancer Research UK
• Cancer screening overview, National Cancer Institute
• Cancer Screening at eMedicine
• ColonCancerCheck including fact sheets in 24 languages at Ontario Ministry of Health and Long-Term Care
• http://www.scotland.gov.uk/Topics/Health/health/cancer/Cancer-Screening/criteria
• How screening recommendations have changed over time from the American Cancer Society