The benefits of cancer appear to be obvious to those whose screening tests have resulted in successful interventions. The concept of detecting cancer early, when tumor is manageable and has not spread from its primary site, rather than late, when it has metastasized to other vital organs, seems reasonable to all layman. So, why do we not offer screening to everyone for every type of cancer in order to detect cancer early? Should we be subjecting everyone to cancer screening when most of them will never get the cancer? How do we justify the costs of screening and the anxiety of a false positive test? The answers to these questions often are different for the many types of cancers.
To begin to answer these questions, it is important to revise the principles of disease screening:
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The disease should be common. |
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The burden of suffering or the morbidity and mortality should be substantial. |
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An effective preventive intervention or treatment should be available. |
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The screening program should be acceptable and available for routine use in the general population. |
It is also important to fully realize what cancer screening is. The simplest explanation of cancer screening is the application of a test to detect a potential cancer where no signs or symptoms of the cancer are present. It is very important to remember that screening is not prevention.
Many patients and layman believe cancer screening to be a cancer prevention measure, and that a positive screening test means that it is a screening failure. Much to the contrary, cancer screening IS to detect cancer, but only hopefully at a stage before it has become systemic, when treatment may be more effective, less expensive, or both. Screening is not diagnosis. Screened individuals can be divided into two groups: those with normal and those with those with abnormal results.
In some individuals with normal results from a screening test (a false negative screening test), cancer may be subsequently detected with diagnostic tests such as biopsy. All individuals with abnormal screening test results require some diagnostic evaluation. Some of those with abnormal results and further diagnostic evaluation will not have cancer (a false positive screening test). Diagnosis is the clinical problem solving process applied to symptomatic individuals or asymptomatic individuals with abnormal screening tests.
It is also important to realize that there are pit falls with cancer screening:
1. Lead time bias - increases the duration between pre-symptomatic disease and onset of symptoms but may not effect the ultimate outcome. |
The time line extends from left to right, showing the onset of cancer, the subsequent clinical diagnosis, and death. The two black dots represent examples of two possible screening test applications.
If a screening test is applied at Screen #1, the time of diagnosis is advanced from the time of usual clinical diagnosis by Lead Time #1. Survival time is apparently increased by this lead time, even though the natural history of the disease is unchanged. If a screening test is applied at Screen #2, the lead time is increased by Lead Time #2.
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Length bias - diseases of longer duration are found easier and screening appears falsely beneficial. Different cancers have different length of disease duration. Screening can sometimes lead to falsely diagnosing illnesses earlier than usual, and while not altering the natural history of the disease, it leads to a longer duration of disease, thereby translating to a longer survival. This is called the length time bias.
It is also important to realize there are target populations for cancer screening, i.e. certain characteristics identify an individual as a candidate for cancer screening. For example, since breast cancer is rare in men, screening is inappropriate in this group.
The target population of a proposed screening strategy defines the characteristics of an individual who would be appropriate to receive the screening test. Typical defining characteristics of a target population include sex, family history, specific known risk factors, geographic region of birth or residence, race or ethnicity, and age.
The success of screening depends on the effectiveness of the screening test. Test results can be either positive or negative. A true positive screening test is an abnormal test for cancer in an individual who subsequently is found to have cancer within a short while whereas a true negative screening test is a normal test for cancer in an individual who subsequently is found not to have cancer the same short defined period of time after the test. Conversely, a false positive screening test is an abnormal test for cancer in an individual who subsequently is found not to have cancer and a false negative screening test is a normal test for cancer in an individual who subsequently is found to have cancer.
The effectiveness can be defined by its sensitivity and specificity, and its positive and negative predictive values. They are defined as the following:
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Sensitivity - proportion of subjects with the disease in the population. Sensitivity is limited by cases missed by the test or false positives. |
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Specificity - proportions of subject without the disease in the population. Incorrectly identified cases or false negatives limit specificity. |
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Positive predictive value (PPV ) - refers to the proportion of individual who test positive with the disease. This is dependent on the prevalence of the disease. |
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Negative predictive value (NPV) - refers to the proportion of individuals who test negative without the disease. |
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So let’s look at all the different screening programs and its benefits. It is not possible to do every cancer, so let’s concentrate on some of the common cancers.
Cancers where cancer screening is established
Breast Cancer
Is it common?
There is no doubt anywhere in the world that breast cancer is common. In Singapore, the period from 1993-1997, it constituted 22.8% of all cancers, and in total approximately 3600 patients was diagnosed with breast cancer (from 1993-1997). The lifetime risk of a woman in Singapore getting breast cancer is 1 in 16-18.
Is it a burden?
Certainly, of the patients who are diagnosed with breast cancer, approximately 1/5 will die from the disease every year.
Is there an effective screening tool?
Several randomized trials of screening for breast cancer have been carried out; the screening modality used being mammograms. There is a clear consensus that such screening programmes are capable of decreasing the risk of mortality from breast cancer in women aged 50 or older. The efficacy of mammogram in women below 50 is still a very controversial issue that results in contradictory recommendations and policies. At best, mortality reduction in this age group would be only 15% or half that of older women. The maximum mortality reduction achievable with mammography is 34% in postmenopausal women.
Colon Cancer
Is it common?
There is no doubt anywhere in the world that colon cancer is also common. The age standardized rates for colon cancer in 1993-1997 demonstrated a 2- fold increase over the risks experienced by Singaporeans in 1968-72. In total, nearly 5000 individuals were diagnosed with colon cancer from 1993-1997. The lifetime risk for the average Singaporean is about 1 in 55.
Is it a burden?
Most certainly.
Is there an effective screening tool?
Colorectal cancer screening has shown: (1) a greater number of earlier cancers (i.e. Stage I or II) detected and this is translated to better survival and cure rates; (2) a greater number of “high risk” colonic polyps detected and removed through the colonoscope before malignant change; (3) to identify a relatively higher risk subgroup of individuals in the population with hitherto no risk factors but found to harbour asymptomatic polyps for regular surveillance. This will effectively keep the risk of developing any advanced cancers very low.
Cervical Cancer
Is it common?
Cervical cancer is the second most common gynaecological cancer in Singapore. Fortunately cervical cancer is now less common than before in Singapore. The age-standardized rates per 100,000 per year have declined from 18.1 between the years 1968-72 to 10.6 between the years 1998-02.
Is it a burden?
Most certainly it is.
Is there an effective screening tool?
Almost all cervical cancer can be prevented. That, is the primary goal of cervical cancer screening. Cervical cancer has a defined premalignant phase quite a long time. At any time, the pre-malignant disease can be treated to prevent it from progressing to invasive cancer There is no doubt that the cancer burden and the mortality from cervical cancer has greatly reduced with screening.
Cancers where cancer screening is promising but yet to be established
Prostate Screening
Although Singaporeans may have one of the lowest incidences and mortality rates of prostate cancer in the world, these rates have risen in the past two decades. This is believed to be due to greater awareness and the wider use of screening as a detection of subclinical lesions.
As it is a disease most likely occurring in elderly men, it is also possible that as people live longer, there are more diagnoses. Screening for prostate cancer is through using blood test (prostate specific antigen) and digital rectal examination. There has yet to be convincing evidence that in Singapore, such screening will lead to true increase in survival of patients diagnosed with all types of prostate cancer through early treatment, rather than just a phenomenon of lead time bias.
However, prostate cancer screening is sometimes hoped to detect more aggressive types of prostate cancer, where early treatment may potentially save lives. The same screening benefits cannot, however, be extrapolated to other lower grades and non-aggressive prostate cancers, where complications of treatment outweigh the benefits.
Further studies are being done to improve screening and treatment, and perhaps in a very near future, more people from the general population in Singapore can be recommended for prostate cancer screening.
Ovarian Cancer Screening
Ovarian cancer has taken over cervical cancer as the fourth commonest cause of cancer in Singapore women. Certainly this is significant, especially in ladies with positive family history of ovarian cancer. There are many large good studies using blood tests (CA125 measurement) and ultrasound of the ovaries to discern if there is any value in screening for ovarian cancer.
The results are promising but still not good enough for it to be recommended for the general population. So many of the screening is still performed under clinical study setting. More is done to research on more sensitive tests.
Lung cancer screening
Majority of lung cancer patients are diagnosed late and the 2-year survival is poor despite treatment with chemotherapy and radiotherapy. However, the 5-year survival is close to 70% if it can be diagnosed early. So there is a pressing need to have effective screening tools for lung cancer to detect it early.
Unfortunately, in the screening studies, significant numbers of patients developed disease before their subsequent scheduled screening. Further, many of the small primary lesions screened had already spread at the time of screening. There is also lead-time bias associated with lung cancer. The lack of sensitive screening is probably because of the natural history of lung cancer rather than poor research and lack of technology.
See Hui Ti
Consultant
Department of Medical Oncology
National Cancer Centre, Singapore
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