Some organs in some individuals are at such high risk of developing cancer that surgical removal of the organ at risk may be considered. Women with severe cervical dysplasia are treated with laser or loop electrosurgical excision or conization and occasionally even hysterectomy. Colectomy is used to prevent colon cancer in patients with familial polyposis or ulcerative colitis.
Prophylactic bilateral mastectomy may be chosen for breast cancer prevention among women with genetic predisposition to breast cancer. In a prospective series of 139 women with BRCA1 and BRCA2 mutations, 76 chose to undergo prophylactic mastectomy and 63 chose close surveillance. At 3 years, no cases of breast cancer had been diagnosed in those opting for surgery, but eight patients in the surveillance group had developed breast cancer. A larger (n = 639) retrospective cohort study reported that three patients developed breast cancer after prophylactic mastectomy compared with an expected incidence of 30–53 cases: a 90–94% reduction in breast cancer risk. Postmastectomy breast cancer–related deaths were reduced by 81–94% for high-risk women compared with sister controls and by 100% for moderate-risk women when compared with expected rates.
Prophylactic oophorectomy may also be employed for the prevention of ovarian and breast cancers among high-risk women. A prospective cohort study evaluating the outcomes of BRCA mutation carriers demonstrated a statistically significant association between prophylactic oophorectomy and a reduced incidence of ovarian or primary peritoneal cancer (36% relative risk reduction, or a 4.5% absolute difference). Studies of prophylactic oophorectomy for prevention of breast cancer in women with genetic mutations have shown relative risk reductions of approximately 50%; the risk reduction may be greatest for women having the procedure at younger (i.e., <50 years) ages.
All of the evidence concerning the use of prophylactic mastectomy and oophorectomy for prevention of breast and ovarian cancer in high-risk women has been observational in nature; such studies are prone to a variety of biases, including case selection bias, family relationships between patients and controls, and inadequate information about hormone use. Thus, they may give an overestimate of the magnitude of benefit.
Screening is a means of detecting disease early in asymptomatic individuals, with the goal of decreasing morbidity and mortality. While screening can potentially reduce disease-specific deaths and has been shown to do so in cervical, colon, lung, and breast cancer, it is also subject to a number of biases that can suggest a benefit when actually there is none. Biases can even mask net harm. Early detection does not in itself confer benefit. Cause-specific mortality, rather than survival after diagnosis, is the preferred endpoint (see below).
Because screening is done on asymptomatic, healthy persons, it should offer substantial likelihood of benefit that outweighs harm. Screening tests and their appropriate use should be carefully evaluated before their use is widely encouraged in screening programs, as a matter of public policy.
A large and increasing number of genetic mutations and nucleotide polymorphisms have been associated with an increased risk of cancer. Testing for these genetic mutations could in theory define a high-risk population. However, most of the identified mutations have very low penetrance and individually provide minimal predictive accuracy. The ability to predict the development of a particular cancer may some day present therapeutic options as well as ethical dilemmas. It may eventually allow for early intervention to prevent a cancer or limit its severity. People at high risk may be ideal candidates for chemoprevention and screening; however, efficacy of these interventions in the high-risk population should be investigated. Currently, persons at high risk for a particular cancer can engage in intensive screening. While this course is clinically reasonable, it is not known if it reduces mortality in these populations.
The accuracy of screening
A screening test’s accuracy or ability to discriminate disease is described by four indices: sensitivity, specificity, positive predictive value, and negative predictive value (Table 28-2). Sensitivity, also called the true-positive rate, is the proportion of persons with the disease who test positive in the screen (i.e., the ability of the test to detect disease when it is present). Specificity, or 1 minus the false-positive rate, is the proportion of persons who do not have the disease that test negative in the screening test (i.e., the ability of a test to correctly identify that the disease is not present). The positive predictive value is the proportion of persons who test positive that actually have the disease. Similarly, negative predictive value is the proportion testing negative that do not have the disease. The sensitivity and specificity of a test are independent of the underlying prevalence (or risk) of the disease in the population screened, but the predictive values depend strongly on the prevalence of the disease.
TABLE 28-2Assessment of the Value of a Diagnostic Testa ||Download (.pdf) TABLE 28-2 Assessment of the Value of a Diagnostic Testa
| ||Condition Present ||Condition Absent |
|Positive test ||a ||b |
|Negative test ||c ||d |
|a = true positive |
|b = false positive |
|c = false negative |
|d = true negative |
|Sensitivity ||The proportion of persons with the condition who test positive: a /(a + c) |
|Specificity ||The proportion of persons without the condition who test negative: d /(b + d) |
|Positive predictive value (PPV) ||The proportion of persons with a positive test who have the condition: a /(a + b) |
|Negative predictive value ||The proportion of persons with a negative test who do not have the condition: d /(c + d) |
Prevalence, sensitivity, and specificity determine PPV
Screening is most beneficial, efficient, and economical when the target disease is common in the population being screened. Specificity is at least as important to the ultimate feasibility and success of a screening test as sensitivity.
Potential biases of screening tests
Common biases of screening are lead time, length-biased sampling, and selection. These biases can make a screening test seem beneficial when actually it is not (or even causes net harm). Whether beneficial or not, screening can create the false impression of an epidemic by increasing the number of cancers diagnosed. It can also produce a shift in the proportion of patients diagnosed at an early stage and inflate survival statistics without reducing mortality (i.e., the number of deaths from a given cancer relative to the number of those at risk for the cancer). In such a case, the apparent duration of survival (measured from date of diagnosis) increases without lives being saved or life expectancy changed.
Lead-time bias occurs whether or not a test influences the natural history of the disease; the patient is merely diagnosed at an earlier date. Survival appears increased even if life is not really prolonged. The screening test only prolongs the time the subject is aware of the disease and spends as a patient.
Length-biased sampling occurs because screening tests generally can more easily detect slow-growing, less aggressive cancers than fast-growing cancers. Cancers diagnosed due to the onset of symptoms between scheduled screenings are on average more aggressive, and treatment outcomes are not as favorable. An extreme form of length bias sampling is termed overdiagnosis, the detection of “pseudo disease.” The reservoir of some undetected slow-growing tumors is large. Many of these tumors fulfill the histologic criteria of cancer but will never become clinically significant or cause death. This problem is compounded by the fact that the most common cancers appear most frequently at ages when competing causes of death are more frequent.
Selection bias must be considered in assessing the results of any screening effort. The population most likely to seek screening may differ from the general population to which the screening test might be applied. In general, volunteers for studies are more health conscious and likely to have a better prognosis or lower mortality rate, irrespective of the screening result. This is termed the healthy volunteer effect.
Potential drawbacks of screening
Risks associated with screening include harm caused by the screening intervention itself, harm due to the further investigation of persons with positive tests (both true and false positives), and harm from the treatment of persons with a true-positive result, whether or not life is extended by treatment (e.g., even if a screening test reduces relative cause-specific mortality by 20–30%, 70–80% of those diagnosed still go on to die of the target cancer). The diagnosis and treatment of cancers that would never have caused medical problems can lead to the harm of unnecessary treatment and give patients the anxiety of a cancer diagnosis. The psychosocial impact of cancer screening can also be substantial when applied to the entire population.
Assessment of screening tests
Good clinical trial design can offset some biases of screening and demonstrate the relative risks and benefits of a screening test. A randomized controlled screening trial with cause-specific mortality as the endpoint provides the strongest support for a screening intervention. Overall mortality should also be reported to detect an adverse effect of screening and treatment on other disease outcomes (e.g., cardiovascular disease). In a randomized trial, two like populations are randomly established. One is given the usual standard of care (which may be no screening at all) and the other receives the screening intervention being assessed. The two populations are compared over time. Efficacy for the population studied is established when the group receiving the screening test has a better cause-specific mortality rate than the control group. Studies showing a reduction in the incidence of advanced-stage disease, improved survival, or a stage shift are weaker (and possibly misleading) evidence of benefit. These latter criteria are early indicators but not sufficient to establish the value of a screening test.
Although a randomized, controlled screening trial provides the strongest evidence to support a screening test, it is not perfect. Unless the trial is population-based, it does not remove the question of generalizability to the target population. Screening trials generally involve thousands of persons and last for years. Less definitive study designs are therefore often used to estimate the effectiveness of screening practices. However, every nonrandomized study design is subject to strong confounders. In descending order of strength, evidence may also be derived from the findings of internally controlled trials using intervention allocation methods other than randomization (e.g., allocation by birth date, date of clinic visit); the findings of analytic observational studies; or the results of multiple time series studies with or without the intervention.
Screening for specific cancers
Screening for cervical, colon, and breast cancer is beneficial for certain age groups. Depending on age and smoking history, lung cancer screening can also be beneficial in specific settings. Special surveillance of those at high risk for a specific cancer because of a family history or a genetic risk factor may be prudent, but few studies have assessed the influence on mortality. A number of organizations have considered whether or not to endorse routine use of certain screening tests. Because these groups have not used the same criteria to judge whether a screening test should be endorsed, they have arrived at different recommendations. The American Cancer Society (ACS) and the U.S. Preventive Services Task Force (USPSTF) publish screening guidelines (Table 28-3); the American Academy of Family Practitioners (AAFP) generally follow/endorse the USPSTF recommendations; and the American College of Physicians (ACP) develops recommendations based on structured reviews of other organizations’ guidelines.
Breast self-examination, clinical breast examination by a caregiver, mammography, and magnetic resonance imaging (MRI) have all been variably advocated as useful screening tools.
A number of trials have suggested that annual or biennial screening with mammography or mammography plus clinical breast examination in normal-risk women older than age 50 years decreases breast cancer mortality. Each trial has been criticized for design flaws. In most trials, breast cancer mortality rate is decreased by 15–30%. Experts disagree on whether average-risk women age 40–49 years should receive regular screening (Table 28-3). The U.K. Age Trial, the only randomized trial of breast cancer screening to specifically evaluate the impact of mammography in women age 40–49 years, found no statistically significant difference in breast cancer mortality for screened women versus controls after about 11 years of follow-up (relative risk 0.83; 95% confidence interval 0.66–1.04); however, <70% of women received screening in the intervention arm, potentially diluting the observed effect. A meta-analysis of eight large randomized trials showed a 15% relative reduction in mortality (relative risk 0.85; 95% confidence interval 0.75–0.96) from mammography screening for women age 39–49 years after 11–20 years of follow-up. This is equivalent to a number needed to invite to screening of 1904 over 10 years to prevent one breast cancer death. At the same time, nearly half of women age 40–49 years screened annually will have false-positive mammograms necessitating further evaluation, often including biopsy. Estimates of overdiagnosis range from 10 to 40% of diagnosed invasive cancers. In the United States, widespread screening over the last several decades has not been accompanied by a reduction in incidence of metastatic breast cancer despite a large increase in early-stage disease, suggesting a substantial amount of overdiagnosis at the population level.
TABLE 28-3Screening Recommendations for Asymptomatic Subjects not Known to be at Increased Risk for the Target Conditiona ||Download (.pdf) TABLE 28-3 Screening Recommendations for Asymptomatic Subjects not Known to be at Increased Risk for the Target Conditiona
|Cancer Type ||Test or Procedure ||USPSTF ||ACS |
|Breast ||Self-examination ||“D” ||Women ≥20 years: Breast self-exam is an option |
| ||Clinical examination ||Women ≥40 years: “I” (as a stand-alone without mammography) || |
Women 20–39 years: Perform every 3 years
Women ≥40 years: Perform annually
| ||Mammography ||Women 40–49 years: The decision should be an individual one, and take patient context/values into account (“C”) ||Women ≥40 years: Screen annually for as long as the woman is in good health |
| || ||Women 50–74 years: Every 2 years (“B”) || |
| || ||Women ≥75 years: “I” || |
| ||Magnetic resonance imaging (MRI) ||“I” ||Women with >20% lifetime risk of breast cancer: Screen with MRI plus mammography annually |
| || || ||Women with 15–20% lifetime risk of breast cancer: Discuss option of MRI plus mammography annually |
| || || ||Women with <15% lifetime risk of breast cancer: Do not screen annually with MRI |
|Cervical ||Pap test (cytology) ||Women 21–65 years: Screen every 3 years (“A”) ||Women 21–29 years: Screen every 3 years |
| || || |
Women <21 years: “D”
Women >65 years, with adequate, normal prior Pap screenings: “D”
Women 30–65 years: Acceptable approach to screen with cytology every 3 years (see HPV test below)
Women <21 years: No screening
Women >65 years: No screening following adequate negative prior screening
| || ||Women after total hysterectomy for noncancerous causes: “D” ||Women after total hysterectomy for noncancerous causes: Do not screen |
| ||HPV test || |
Women 30–65 years: Screen in combination with cytology every 5 years if woman desires to lengthen the screening interval (see Pap test, above) (“A”)
Women <30 years: “D”
Women >65 years, with adequate, normal prior Pap screenings: “D”
Women after total hysterectomy for noncancerous causes: “D”
Women 30–65 years: Preferred approach to screen with HPV and cytology co-testing every 5 years (see Pap test above)
Women <30 years: Do not use HPV testing
Women >65 years: No screening following adequate negative prior screening
Women after total hysterectomy for noncancerous causes: Do not screen
|Colorectal ||Sigmoidoscopy ||Adults 50–75 years: every 5 years in combination with high-sensitivity FOBT every 3 years (“A”)b ||Adults ≥50 years: Screen every 5 years |
| || ||Adults 76–85 years: “C” || |
| || ||Adults ≥85 years: “D” || |
| ||Fecal occult blood testing (FOBT) ||Adults 50–75 years: Annually, for high-sensitivity FOBT (“A”) ||Adults ≥50 years: Screen every year |
| || ||Adults 76–85 years: “C” || |
| || ||Adults ≥85 years: “D” || |
| ||Colonoscopy ||Adults 50–75 years: every 10 years (“A”) ||Adults ≥50 years: Screen every 10 years |
| || ||Adults 76–85 years: “C” || |
| || ||Adults ≥85 years: “D” || |
| ||Fecal DNA testing ||“I” ||Adults ≥50 years: Screen, but interval uncertain |
| ||Fecal immunochemical testing (FIT) ||“I” ||Adults ≥50 years: Screen every year |
| ||CT colonography ||“I” ||Adults ≥50 years: Screen every 5 years |
|Lung ||Low-dose computed tomography (CT) scan ||Adults 55–80 years, with a ≥30 pack-year smoking history, still smoking or have quit within past 15 years. Discontinue once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability to have curative lung surgery: “B” ||Men and women, 55–74 years, with ≥30 pack-year smoking history, still smoking or have quit within past 15 years: Discuss benefits, limitations, and potential harms of screening; only perform screening in facilities with the right type of CT scanner and with high expertise/specialists |
|Ovarian || |
|There is no sufficiently accurate test proven effective in the early detection of ovarian cancer. For women at high risk of ovarian cancer and/or who have unexplained, persistent symptoms, the combination of CA-125 and transvaginal ultrasound with pelvic exam may be offered. |
|Prostate ||Prostate-specific antigen (PSA) ||Men, all ages: “D” ||Starting at age 50, men should talk to a doctor about the pros and cons of testing so they can decide if testing is the right choice for them. If African American or have a father or brother who had prostate cancer before age 65, men should have this talk starting at age 45. How often they are tested will depend on their PSA level. |
| ||Digital rectal examination (DRE) ||No individual recommendation ||As for PSA; if men decide to be tested, they should have the PSA blood test with or without a rectal exam |
|Skin ||Complete skin examination by clinician or patient ||“I” ||Self-examination monthly; clinical exam as part of routine cancer-related checkup |
No study of breast self-examination has shown it to decrease mortality. A randomized controlled trial of approximately 266,000 women in China demonstrated no difference in breast cancer mortality between a group that received intensive breast self-exam instruction and reinforcement/reminders and controls at 10 years of follow-up. However, more benign breast lesions were discovered and more breast biopsies were performed in the self-examination arm.
Genetic screening for BRCA1 and BRCA2 mutations and other markers of breast cancer risk has identified a group of women at high risk for breast cancer. Unfortunately, when to begin and the optimal frequency of screening have not been defined. Mammography is less sensitive at detecting breast cancers in women carrying BRCA1 and BRCA2 mutations, possibly because such cancers occur in younger women, in whom mammography is known to be less sensitive. MRI screening may be more sensitive than mammography in women at high risk due to genetic predisposition or in women with very dense breast tissue, but specificity may be lower. An increase in overdiagnosis may accompany the higher sensitivity. The impact of MRI on breast cancer mortality with or without concomitant use of mammography has not been evaluated in a randomized controlled trial.
Screening with Papanicolaou (Pap) smears decreases cervical cancer mortality. The cervical cancer mortality rate has fallen substantially since the widespread use of the Pap smear. With the onset of sexual activity comes the risk of sexual transmission of HPV, the fundamental etiologic factor for cervical cancer. Screening guidelines recommend regular Pap testing for all women who have reached the age of 21 (prior to this age, even in individuals that have begun sexual activity, screening may cause more harm than benefit). The recommended interval for Pap screening is 3 years. Screening more frequently adds little benefit but leads to important harms, including unnecessary procedures and overtreatment of transient lesions. Beginning at age 30, guidelines also offer the alternative of combined Pap smear and HPV testing for women. The screening interval for women who test normal using this approach may be lengthened to 5 years.
An upper age limit at which screening ceases to be effective is not known, but women age 65 years with no abnormal results in the previous 10 years may choose to stop screening. Screening should be discontinued in women who have undergone a hysterectomy for noncancerous reasons.
Although the efficacy of the Pap smear in reducing cervical cancer mortality has never been directly confirmed in a randomized, controlled setting, a clustered randomized trial in India evaluated the impact of one-time cervical visual inspection and immediate colposcopy, biopsy, and/or cryotherapy (where indicated) versus counseling on cervical cancer deaths in women age 30–59 years. After 7 years of follow-up, the age-standardized rate of death due to cervical cancer was 39.6 per 100,000 person-years in the intervention group versus 56.7 per 100,000 person-years in controls.
Fecal occult blood testing (FOBT), digital rectal examination (DRE), rigid and flexible sigmoidoscopy, colonoscopy, and computed tomography (CT) colonography have been considered for colorectal cancer screening. A meta-analysis of four randomized controlled trials demonstrated a 15% relative reduction in colorectal cancer mortality with FOBT. The sensitivity for FOBT is increased if specimens are rehydrated before testing, but at the cost of lower specificity. The false-positive rate for rehydrated FOBT is high; 1–5% of persons tested have a positive test. Only 2–10% of those with occult blood in the stool have cancer. The high false-positive rate of FOBT dramatically increases the number of colonoscopies performed.
Fecal immunochemical tests appear to have higher sensitivity for colorectal cancer than nonrehydrated FOBT tests. Fecal DNA testing is an emerging testing modality; it may have increased sensitivity and comparable specificity to FOBT and could potentially reduce harms associated with follow-up of false-positive tests. The body of evidence on the operating characteristics and effectiveness of fecal DNA tests in reducing colorectal cancer mortality is limited.
Two meta-analyses of five randomized controlled trials of sigmoidoscopy (i.e., the NORCCAP, SCORE, PLCO, Telemark, and U.K. trials) found an 18% relative reduction in colorectal cancer incidence and a 28% relative reduction in colorectal cancer mortality. Participant ages ranged from 50 to 74 years, with follow-up ranging from 6 to 13 years. Diagnosis of adenomatous polyps by sigmoidoscopy should lead to evaluation of the entire colon with colonoscopy. The most efficient interval for screening sigmoidoscopy is unknown, but an interval of 5 years is often recommended. Case-control studies suggest that intervals of up to 15 years may confer benefit; the U.K. trial demonstrated benefit with one-time screening.
One-time colonoscopy detects ~25% more advanced lesions (polyps >10 mm, villous adenomas, adenomatous polyps with high-grade dysplasia, invasive cancer) than one-time FOBT with sigmoidoscopy; comparative programmatic performance of the two modalities over time is not known. Perforation rates are about 3/1000 for colonoscopy and 1/1000 for sigmoidoscopy. Debate continues on whether colonoscopy is too expensive and invasive and whether sufficient provider capacity exists to be recommended as the preferred screening tool in standard-risk populations. Some observational studies suggest that efficacy of colonoscopy to decrease colorectal cancer mortality is primarily limited to the left side of the colon.
CT colonography, if done at expert centers, appears to have a sensitivity for polyps ≥6 mm comparable to colonoscopy. However, the rate of extracolonic findings of abnormalities of uncertain significance that must nevertheless be worked up is high (~15–30%); the long-term cumulative radiation risk of repeated colonography screenings is also a concern.
Chest x-ray and sputum cytology have been evaluated in several randomized lung cancer screening trials. The most recent and largest (n = 154,901) of these, one substudy of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, found that, compared with usual care, annual chest x-ray did not reduce the risk of dying from lung cancer (relative risk 0.99; 95% confidence interval 0.87–1.22) after 13 years. Low-dose CT has also been evaluated in several randomized trials. The largest and longest of these, the National Lung Screening Trial (NLST), was a randomized controlled trial of screening for lung cancer in approximately 53,000 persons age 55–74 years with a 30+ pack-year smoking history. It demonstrated a statistically significant relative reduction of about 15–20% in lung cancer mortality in the CT arm compared to the chest x-ray arm (or about 3 fewer deaths per 1000 people screened with CT). However, the harms include the potential radiation risks associated with multiple scans, the discovery of incidental findings of unclear significance, and a high rate of false-positive test results. Both incidental findings and false-positive tests can lead to invasive diagnostic procedures associated with anxiety, expense, and complications (e.g., pneumo- or hemothorax after lung biopsy). The NLST was performed at experienced screening centers, and the balance of benefits and harms may differ in the community setting at less experienced centers.
Adnexal palpation, transvaginal ultrasound (TVUS), and serum CA-125 assay have been considered for ovarian cancer screening. A large randomized controlled trial has shown that an annual screening program of TVUS and CA-125 in average-risk women does not reduce deaths from ovarian cancer (relative risk 1.21; 95% confidence interval 0.99–1.48). Adnexal palpation was dropped early in the study because it did not detect any ovarian cancers that were not detected by either TVUS or CA-125. The risks and costs associated with the high number of false-positive results are impediments to routine use of these modalities for screening. In the PLCO trial, 10% of participants had a false-positive result from TVUS or CA-125, and one-third of these women underwent a major surgical procedure; the ratio of surgeries to screen-detected ovarian cancer was approximately 20:1.
The most common prostate cancer screening modalities are DRE and serum PSA assay. An emphasis on PSA screening has caused prostate cancer to become the most common nonskin cancer diagnosed in American males. This disease is prone to lead-time bias, length bias, and overdiagnosis, and substantial debate continues among experts as to whether screening should be offered unless the patient specifically asks to be screened. Virtually all organizations stress the importance of informing men about the uncertainty regarding screening efficacy and the harms associated with screening. Prostate cancer screening clearly detects many asymptomatic cancers, but the ability to distinguish tumors that are lethal but still curable from those that pose little or no threat to health is limited, and randomized trials indicate that the effect of PSA screening on prostate cancer mortality across a population is, at best, small. Men older than age 50 years have a high prevalence of indolent, clinically insignificant prostate cancers (about 30–50% of men, increasing further as men age).
Two major randomized controlled trials of the impact of PSA screening on prostate cancer mortality have been published. The PLCO Cancer Screening Trial was a multicenter U.S. trial that randomized almost 77,000 men age 55–74 years to receive either annual PSA testing for 6 years or usual care. At 13 years of follow-up, no statistically significant difference in the number of prostate cancer deaths were noted between the arms (rate ratio 1.09; 95% confidence interval 0.87–1.36). Approximately 50% of men in the control arm received at least one PSA test during the trial, which may have potentially diluted a small effect.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) was a multinational study that randomized approximately 182,000 men between age 50 and 74 years (with a predefined “core” screening group of men age 55–69 years) to receive PSA testing or no screening. Recruitment and randomization procedures, as well as actual frequency of PSA testing, varied by country. After a median follow-up of 11 years, a 20% relative reduction in the risk of prostate cancer death in the screened arm was noted in the “core” screening group. The trial found that 1055 men would need to be invited to screening, and 37 cases of prostate cancer detected, to avert 1 death from prostate cancer. Of the seven countries included in the mortality analysis, two demonstrated statistically significant reductions in prostate cancer deaths, whereas five did not. There was also an imbalance in treatment between the two study arms, with a higher proportion of men with clinically localized cancer receiving radical prostatectomy in the screening arm and receiving it at experienced referral centers.
Treatments for low-stage prostate cancer, such as surgery and radiation therapy, can cause significant morbidity, including impotence and urinary incontinence. In a trial conducted in the United States after the initiation of widespread PSA testing, random assignment to radical prostatectomy compared with “watchful waiting” did not result in a statistically significant decrease in prostate cancer deaths (absolute risk reduction 2.7%; 95% confidence interval–1.3 to 6.2%).
Visual examination of all skin surfaces by the patient or by a health care provider is used in screening for basal and squamous cell cancers and melanoma. No prospective randomized study has been performed to look for a mortality decrease. Unfortunately, screening is associated with a substantial rate of overdiagnosis.