Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program (2005)

“Good: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.

“Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.

“Poor: Evidence is insufficient to assess the effects on health outcomes because of the low number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.”

“A. The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.

“B. The USPSTF recommends that clinicians provide [this service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

“C. The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

“D. The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

“E. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.”

“I. Evidence from at least 1 properly randomized controlled trial (RCT).

“II-1. Evidence from well-designed controlled trials without randomization.

“II.2. Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 center or research group.

“II-3. Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.

“III. Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.”

“A. Good evidence to support the recommendation that the condition be specifically considered in a Periodic Health Examination (PHE).

“B. Fair evidence to support the recommendation that the condition be specifically considered in a PHE.

“C. Poor evidence regarding inclusion or exclusion of a condition in a PHE, but recommendations may be made on other grounds.

“D. Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

“E. Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.”

No information available.

Fair evidence to exclude from Periodic Health Examination (PHE) for general population (D); poor evidence to include or exclude from the PHE for persons at high risk (C).

The USPSTF recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older.

Rating: B recommendation.

Rationale: The USPSTF found fair evidence that mammography screening every 12-33 months significantly reduces mortality from breast cancer. Evidence is strongest for women aged 50-69, the age group generally included in screening trials. For women aged 40-49, the evidence that screening mammography reduces mortality from breast cancer is weaker, and the absolute benefit of mammography is smaller than it is for older women. Most, but not all, studies indicate a mortality benefit for women undergoing mammography at ages 40-49, but the delay in observed benefit in women younger than 50 makes it difficult to determine the incremental benefit of beginning screening at age 40 rather than at age 50.

The absolute benefit is smaller because the incidence of breast cancer is lower among women in their 40s than it is among older women. The USPSTF concluded that the evidence is also generalizable to women aged 70 and older (who face a higher absolute risk for breast cancer) if their life expectancy is not compromised by comorbid disease. The absolute probability of benefits of regular mammography increase along a continuum with age,

whereas the likelihood of harms from screening (false-positive results and unnecessary anxiety, biopsies, and cost) diminish from ages 40-70. The balance of benefits and potential harms, therefore, grows more favorable as women age. The precise age at which the potential benefits of mammography justify the possible harms is a subjective choice. The USPSTF did not find sufficient evidence to specify the optimal screening interval for women aged 40-49 (see Clinical Considerations).

The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer.

Rating: I recommendation.

Rationale: No screening trial has examined the benefits of CBE alone (without accompanying mammography) compared to no screening, and design characteristics limit the generalizability of studies that have examined CBE. The USPSTF could not determine the benefits of CBE alone or the incremental benefit of adding CBE to mammography. The USPSTF therefore could not determine whether potential benefits of routine CBE outweigh the potential harms.

The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination (BSE).

Rating: I recommendation.

Rationale: The USPSTF found poor evidence to determine whether BSE reduces breast cancer mortality. The USPSTF found fair evidence that BSE is associated with an increased risk for false-positive results and biopsies. Due to design limitations of published and ongoing studies of BSE, the USPSTF could not determine the balance of benefits and potential harms of BSE.

The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix.

Rating: A recommendation.

Rationale: The USPSTF found good evidence from multiple observational studies that screening with cervical cytology (Pap smears) reduces incidence of and mortality from cervical cancer. Direct evidence to determine the optimal starting and stopping age and interval for screening is limited. Indirect evidence suggests most of the benefit can be obtained by beginning screening within 3 years of onset of sexual activity or age 21 (whichever comes first) and screening at least every 3 years (go to Clinical Considerations). The USPSTF concludes that the benefits of screening substantially outweigh potential harms.

The USPSTF recommends against routinely screening women older than age 65 for cervical cancer if they have had adequate recent screening with normal Pap smears and are not otherwise at high risk for cervical cancer (go to Clinical Considerations).

Rating: D recommendation

Rationale: The USPSTF found limited evidence to determine the benefits of continued screening in women older than 65. The yield of screening is low in previously screened women older than 65 due to the declining incidence of high-grade cervical lesions after middle age. There is fair evidence that screening women older than 65 is associated with an increased risk for potential harms, including false-positive results and invasive procedures. The USPSTF concludes that the potential harms of screening are likely to exceed benefits among older women who have had normal results previously and who are not otherwise at high risk for cervical cancer.

The USPSTF recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease.

Rating: D recommendation.

Rationale: The USPSTF found fair evidence that the yield of cytologic screening is very low in women after hysterectomy and poor evidence that screening to detect vaginal cancer improves health outcomes. The USPSTF concludes that potential harms of continued screening after hysterectomy are likely to exceed benefits.

The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer.

Rating: I recommendation

Rationale: The USPSTF found poor evidence to determine whether new technologies, such as liquid-based cytology, computerized rescreening, and algorithm based screening, are more effective than conventional Pap smear screening in reducing incidence of or mortality from invasive cervical cancer. Evidence to determine both sensitivity and specificity of new screening technologies is limited. As a result, the USPSTF concludes that it cannot determine whether the potential benefits of new screening devices relative to conventional Pap tests are sufficient to justify a possible increase in potential harms or costs.

The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of human papillomavirus (HPV) testing as a primary screening test for cervical cancer.

Rating: I recommendation.

Rationale: The USPSTF found poor evidence to determine the benefits and potential harms of HPV screening as an adjunct or alternative to regular Pap smear screening. Trials are underway that should soon clarify the role of HPV testing in cervical cancer screening.

Fair evidence to include in periodic health examination of sexually active women. (B)

The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer.

Rating: A recommendation.

Rationale: The USPSTF found fair to good evidence that several screening methods are effective in reducing mortality from colorectal cancer. The USPSTF concluded that the benefits from screening substantially outweigh potential harms, but the quality of evidence, magnitude of benefit, and potential harms vary with each method.

The USPSTF found good evidence that periodic fecal occult blood testing (FOBT) reduces mortality from colorectal cancer and fair evidence that sigmoidoscopy alone or in combination with FOBT reduces mortality. The

USPSTF did not find direct evidence that screening colonoscopy is effective in reducing colorectal cancer mortality; efficacy of colonoscopy is supported by its integral role in trials of FOBT, extrapolation from sigmoidoscopy studies, limited case-control evidence, and the ability of colonoscopy to inspect the proximal colon. Double-contrast barium enema offers an alternative means of whole-bowel examination, but it is less sensitive than colonoscopy, and there is no direct evidence that it is effective in reducing mortality rates. The USPSTF found insufficient evidence that newer screening technologies (for example, computed tomographic colography) are effective in improving health outcomes.

There are insufficient data to determine which strategy is best in terms of the balance of benefits and potential harms or cost-effectiveness. Studies reviewed by the USPSTF indicate that colorectal cancer screening is likely to be cost-effective (less than $30,000 per additional year of life gained) regardless of the strategy chosen.

It is unclear whether the increased accuracy of colonoscopy compared with alternative screening methods (for example, the identification of lesions that FOBT and flexible sigmoidoscopy would not detect) offsets the procedure’s additional complications, inconvenience, and costs.

Average Risk Individuals

• Screening with the Hemoccult test: There is good evidence to include screening with Hemoccult test in the periodic health examination of asymptomatic patients over age 50 with no other risk factors [A, I]. However, there remain concerns about the high rate of false-positive results, feasibility and small clinical benefit of such screening (over 1000 individuals must be screened for 10 years to avert one death from colorectal cancer). For patients being screened with Hemoccult, it is recommended that they avoid red meat, cantaloupe and melons, raw turnip, radishes, broccoli and cauliflower, vitamin C supplements and aspirin and non-steroidal anti-inflammatory drugs for 3 days before fecal samples are collected. However, a recent metaanalysis of 4 RCTs found no improvement in positivity rates or change in compliance rates with moderate dietary restrictions.

• Screening with sigmoidoscopy: There is evidence from case control studies, to recommend that flexible sigmoidoscopy be included in the periodic health examination of patients over age 50 [B, II-2, III]. There is insufficient evidence to make recommendations about whether only 1 or both of FOBT and sigmoidoscopy should be performed [C, I].

• Screening with colonoscopy: There is insufficient evidence to include or exclude colonoscopy as an initial screen in the periodic health examination

[C, II-3]. Although colonoscopy is the best method for detecting adenomas and carcinomas, it may not be feasible to screen asymptomatic patients because of patient compliance and the expertise and equipment required and the potential costs. On the other hand, if colonoscopy were an effective screening strategy when performed at less frequent intervals, these issues might be of less concern.

Above Average Risk Individuals

• Individuals at Risk for Familial Adenomatous Polyposis (FAP): The Task Force recommends genetic testing of individuals at risk for FAP if the genetic mutation has been identified in the family and if genetic testing is available [B, II-3]. If the individual carries the mutation, then he or she should be screened with flexible sigmoidoscopy beginning at puberty [B, II-3]. Individuals from families where the gene mutation has been identified but are negative themselves, require screening similar to the average risk population. For at risk individuals where the mutation has not been identified in the family or where genetic testing is not available, screening with annual or biannual flexible sigmoidoscopy should be undertaken beginning at puberty. In all instances, genetic counseling should be performed prior to genetic testing.

• Individuals at Risk for Hereditary Non-Polyposis Colon Cancer (HNPCC): Patients in kindreds with the cancer family syndrome (HNPCC) have a high risk of colorectal cancer and a high incidence of right-sided colon cancer. Thus, colonoscopy rather than sigmoidoscopy is recommended for screening such patients. Based on Level III evidence, the Task Force recommends screening with colonoscopy in individuals from HNPCC kindreds [B, II-3]. Although higher levels of evidence are usually required to give a B recommendation, the Task Force realizes that it is unlikely that more rigorous studies could be performed in this cohort of patients given the high risk of cancer and relative infrequency of HNPCC. The ages when screening should begin and the frequency at which colonoscopy should be performed are unclear.

• Individuals with a Family History of Polyps or Colon Cancer: Patients who have only one or two first-degree relatives with colorectal cancer should be screened in the same way as average risk individuals. There is insufficient evidence to recommend colonoscopy for individuals who have a family history of colorectal polyps or cancer but do not fit the criteria for HNPCC [C, III]. While there is evidence that there is an increased prevalence of neoplasms in these individuals, there is insufficient information to recommend more intense screening than that of individuals at average risk. Further delineation of the risk for individuals with multiple affected family members and family members with early age of diagnosis of colorectal cancer is necessary.

• Because most screening options are multiphasic, it is preferable that there is adequate infrastructure to support the implementation, assure quality control and the timely follow-up of screened individuals.

The USPSTF concludes that the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer with either low dose computerized tomography (LDCT), chest x-ray (CXR), sputum cytology, or a combination of these tests.

Rating: I Recommendation.

Rationale: The USPSTF found fair evidence that screening with LDCT, CXR, or sputum cytology can detect lung cancer at an earlier stage than lung cancer would be detected in an unscreened population; however, the USPSTF found poor evidence that any screening strategy for lung cancer decreases mortality. Because of the invasive nature of diagnostic testing and the possibility of a high number of false-positive tests in certain populations, there is potential for significant harms from screening. Therefore, the USPSTF could not determine the balance between the benefits and harms of screening for lung cancer.

The USPSTF concludes that the evidence is insufficient to recommend for or against routinely screening adults for oral cancer.

Rating: I Recommendation.

Rationale: The USPSTF found no new good-quality evidence that screening for oral cancer leads to improved health outcomes for either high-risk adults (i.e., those over the age of 50 who use tobacco) or for average-risk adults in the general population. It is unlikely that controlled trials of screening for oral cancer will ever be conducted in the general population because of the very low incidence of oral cancer in the United States. There is also no new evidence for the harms of screening. As a result, the USPSTF could not determine the balance between benefits and harms.

With respect to screening by oral physical exam in 1994: Insufficient evidence to include or exclude from periodic health exam (C); annual examina-

tion by physician and/or dentist should be considered for men and women over age 60 years with risk factors for oral cancers and precancers; individual judgment should be exercised regarding the use of tolonium chloride for those identified as positive by oral physical exam.

The above recommendation has been updated in 1999

• Population screening: Fair evidence to exclude screening the general population for oral cancer by clinical examination (D Recommendation).

• Opportunistic screening: Insufficient evidence to recommend inclusion or exclusion of screening for oral cancer by clinical examination of asymptomatic patients (C Recommendation).

• For high risk patients, annual examination by physician or dentist should be considered. Major risk factors include a history of tobacco use and excessive alcohol consumption.

The USPSTF recommends against routine screening for ovarian cancer.

Rating: D Recommendation.

Rationale: The USPSTF found fair evidence that screening with serum CA-125 level or transvaginal ultrasound can detect ovarian cancer at an earlier stage than it can be detected in the absence of screening; however, the USPSTF found fair evidence that earlier detection would likely have a small effect, at best, on mortality from ovarian cancer. Because of the low prevalence of ovarian cancer and the invasive nature of diagnostic testing after a positive screening test, there is fair evidence that screening could likely lead to important harms. The USPSTF concluded that the potential harms outweigh the potential benefits.

The USPSTF recommends against routine screening for pancreatic cancer in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers.

Rating: D Recommendation.

Rationale: The USPSTF found no evidence that screening for pancreatic cancer is effective in reducing mortality. There is a potential for significant harm due to the very low prevalence of pancreatic cancer, limited accuracy

of available screening tests, the invasive nature of diagnostic tests, and the poor outcomes of treatment. As a result, the USPSTF concluded that the harms of screening for pancreatic cancer exceed any potential benefits.

There is fair evidence that routine screening should be excluded from the periodic health examination (D Recommendation).

The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE).

Rating: I recommendation.

Rationale: The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies, and potential complications of treatment of some cancers that may never have affected a patient’s health. The USPSTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population.

The alternate view considers early detection and treatment as a single package and asks whether there is evidence that such combined efforts do more good than harm. This is the question of greatest importance, both from the individual patient’s perspective as well as that of the population. Hence, while evaluating the performance of early detection tests is part of the picture, one must also evaluate the effectiveness of therapy and whether the use of available early detection tests ultimately provides overall net benefit to the

patient. This is the view taken by the Canadian Task Force on the Periodic Health Examination.

Based on the absence of evidence for effectiveness of therapy and the substantial risk of adverse effects associated with such therapy; and the poor predictive value of screening tests, there is at present insufficient evidence to support wide-spread initiatives for the early detection of prostate cancer.

The Task Force does not recommend the routine use of PSA as part of a periodic health examination. While PSA can detect earlier cancer, it is associated with a substantial false positive rate. This, combined with poor evidence to support the effectiveness of subsequent therapy and clear evidence of substantial risk associated with such therapy, means that the widespread implementation of PSA would expose more men to uncertain benefit, but to definite risks. For these reasons the Task Force recommends that PSA be excluded from the periodic health examination (D Recommendation).

• Based on the available evidence for TRUS, the Task Force recommends against the routine use of this procedure as part of a periodic health examination (D Recommendation).

These recommendations are made on the basis of the evaluation of the best available evidence using the Canadian Task Force guidelines, and the ethical imperative that early detection efforts must be proven to result in more good than harm before being incorporated into the periodic health examination.

The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for skin cancer using a total-body skin examination

for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer.

Rating: I recommendation.

Rationale: Evidence is lacking that skin examination by clinicians is effective in reducing mortality or morbidity from skin cancer. The USPSTF could not determine the benefits and harms of periodic skin examination. (See Clinical Considerations for discussion of selected populations at high risk.)

Benefits from screening are unproven, even in high-risk patients.

Clinicians should be aware that fair-skinned men and women aged >65, patients with atypical moles, and those with >50 moles constitute known groups at substantially increased risk for melanoma.

Asymmetry, border irregularity, color variability, diameter >6 mm (“A,” “B,” “C,” “D”), or rapidly changing lesions are features associated with an increased risk of malignancy. Suspicious lesions should be biopsied.

Routine screening for skin cancer by primary care providers using total-body skin examination is not recommended for the general population. Clinicians should remain alert for skin lesions with malignant features (i.e. asymmetry, border irregularity, color variability, diameter greater than 6 mm, or rapidly changing lesions) when examining patients for other reasons, particularly in those with established risk factors. Such risk factors include clinical evidence of melanocytic precursor or marker lesions (i.e. atypical moles, certain congenital moles), large numbers of common moles, immunosuppression, a family or personal history of skin cancer, substantial cumulative lifetime sun exposure, intermittent intense sun exposure or severe sunburns in childhood, or light skin, hair, and eye color, freckles, or poor tanning ability. Appropriate biopsy specimens should be taken of suspicious lesions (C Recommendation).

Currently, there is insufficient evidence to recommend for or against counseling patients to perform periodic self-examination of the skin. Clinicians may wish to educate patients with established risk factors for skin cancer (see above) concerning signs and symptoms suggesting cutaneous malignancy and the possible benefits of periodic self-examination (C Recommendation).

Persons with Family Melanoma Syndrome are at substantially increased risk for malignant melanoma. Clinicians examining these patients should be particularly alert to skin lesions with malignant features and should consider referral to skin cancer specialists for evaluation. For this very select subgroup there is fair evidence to offer total body skin examination (B Recommendation).

The USPSTF recommends against routine screening for testicular cancer in asymptomatic adolescent and adult males.

Rating: D Recommendation

Rationale: The USPSTF found no new evidence that screening with clinical examination or testicular self-examination is effective in reducing mortality from testicular cancer. Even in the absence of screening, the current treatment interventions provide very favorable health outcomes. Given the low prevalence of testicular cancer, limited accuracy of screening tests, and no evidence for the incremental benefits of screening, the USPSTF concluded that the harms of screening exceed any potential benefits.

Because no studies of screening for testicular cancer by physician or patient self-examination have been reported, there is insufficient evidence to include or exclude screening for this cancer in the periodic health examination of men (C Recommendation). Based on the low incidence of disease and the current high cure rate it is unlikely formal screening would improve the already excellent prognosis. Patients with a history of cryptorchidism, orchiopexy, or testicular atrophy should be informed of their increased risk for developing testicular cancer and counselled about screening options. The optimal frequency of such examinations has not been determined and is left to clinical discretion. Clinicians should advise adolescent and young adult males to seek prompt medical attention if a testicular mass is noted.