Whether one test is more effective than another is unclear, but it is clear that these options are only relatively comparable over the long term if the recommended regimens are followed. A single colonoscopic examination is considered the most accurate test, but repeated colonoscopies do not necessarily detect more cancers than the other testing strategies when conducted every 10 years for several decades. Because DCBE has demonstrated lower sensitivity compared with colonoscopy, the interval for its use in screening was changed from every 5 or 10 years to every 5 years when the US Multisociety Task Force on Colorectal Cancer updated its guidelines for colorectal cancer screening in 2003.⁷

Colonoscopy now dominates all strategies for high-risk screening and surveillance; aside from accuracy, a strong benefit is the ability to sample or remove lesions during screening. However, because no randomized controlled clinical trials have been done to evaluate the effectiveness of colonoscopy for colon cancer screening, the USPSTF notes a lack of direct evidence that colonoscopy is effective in reducing colorectal cancer mortality.⁶

A recent study showed that women in particular may benefit from screening with colonoscopy rather than flexible sigmoidoscopy.⁸ Investigators compared the diagnostic yield of screening colonoscopy in 1463 average-risk women to that of average-risk male counterparts in a previous Veterans Affairs study.⁹ They found that the diagnostic yield of flexible sigmoidoscopy for advanced neoplasia is much lower among women than among men (35.2% versus 66.3%, P<.001) and concluded that flexible sigmoidoscopy is an inadequate method of predicting advanced neoplasia in the proximal colon of women. This study suggests that gender may someday be a factor in test suitability, although it should be noted that the presence of advanced neoplasia overall in this sample of women was relatively low.

Test choice may also be influenced by physician and patient comfort, availability, access, benefit-to-risk ratio, cost, sensitivity, specificity, and insurance coverage. For example, patients who fear or refuse colonoscopy may be more inclined to accept annual FOBT; others may choose flexible sigmoidoscopy every 5 years if colonoscopy is not accepted by their insurance plan. All these tests are included in the major guidelines.^4-7 They are also all underutilized, as evidenced by a high rate of avoidable advanced cancers.

A positive FOBT, FIT, or DCBE screening result should be followed by colonoscopy because of the possibility that a significant lesion will be visualized and a biopsy will need to be performed. The recommendation for follow-up of abnormalities detected by flexible sigmoidoscopy is less clear. According to the US Multisociety Task Force on Colorectal Cancer, the decision to perform colonoscopy following such results is controversial and should be individualized based on risk factors associated with increased risk of advanced proximal neoplasia—older than 65, villous histology in distal adenomas, and/or adenomas 1 cm or more in size, multiple distal adenomas, and a positive family history of colorectal cancer.^7,10 The recommendation is based on evidence that hyperplastic polyps are not associated with increased risk of advanced proximal neoplasia.

Screening tests no longer recommended

Digital rectal exams (DRE), toilet bowl FOBT, and in-office single-panel FOBT for colon cancer screening are not recommended due to the high number of false-negative findings that they yield. DRE is not proven for colorectal screening and is not associated with reduction in mortality from distal rectal cancer. If the patient and physician determine that FOBT is the preferred colon screening test, only the at-home procedure following manufacturer's recommendations should be used, and annual testing must be done. Negative results from digital in-office FOBT do not decrease the odds of advanced neoplasia.¹¹

Emerging technologies

New modalities show promise in colon cancer screening, as they are considered less invasive, more accurate, and more palatable to patients. With further study, CT colonography and stool DNA testing may soon join other tests as part of the guideline-based approach to detecting early cancer in average-risk patients.

FIT Older guaiac-based FOBT tests have a poor test sensitivity for premalignant and early-stage lesions, and irregular testing limits the potential to detect colorectal cancer early. Newer FITs are reported to have improved performance characteristics compared to guaiac tests, and they do not require dietary restrictions. If hemoglobin is present in the stool, the monoclonal and/or polyclonal antibodies employed by such tests will attach to its antigens, showing a positive result.¹² FITs do not react with nonhuman hemoglobin or uncooked fruits and vegetables with peroxidase activity known to cause false-positive results on guaiac-based tests. Such tests are also more specific, because they do not respond to upper GI bleeding.

In a study of InSure, an immunochemical FOBT approved in 2001, in a normal patient population 40 and older, specificity was 97.9%; in a population younger than 30, specificity was 97.8%.¹² The lower false-positive rate associated with FITs translates into a lower rate of unnecessary colonoscopy. In addition, the improved sensitivity of the newer tests may compensate for the nonadherence associated with traditional FOBT testing, leading to greater program sensitivity. According to the ACS, immunochemical tests are more patient-friendly and are likely to be equal or better in sensitivity and specificity than guaiac-based tests for the detection of occult blood.¹³

Stool DNA testing New testing for DNA mutations in stool have the potential to identify cancers and advanced lesions that would not otherwise be identified. DNA has proven to be a good marker, as it is stable in the stool, is shed continuously, and can be detected in small amounts. In addition, the test does not require dietary restrictions or bowel preparation. Early clinical trials have shown that these tests outperform guaiac-based FOBT on 1-time testing in terms of sensitivity for both colorectal cancer and premalignant adenomatous polyps.¹²

The test is expensive (more than $750) and requires an entire bowel movement, which may influence adherence. Until more studies are conducted in average-risk patients and the most appropriate markers for DNA detection of cancer are identified, the use of stool DNA mutation testing cannot be recommended. A large National Cancer Institute trial is under way.

CT colonography The lack of evidence regarding CT colonography, also known as virtual colonoscopy, precludes its use for general screening for now. According to the USPSTF, the impressive sensitivity and specificity in research findings (85-90%) do not match real-world outcomes, where results are influenced by the skill of the examiner.⁶ Also, only frank colon cancers and larger polyps—not small and flat ones—are well-visualized on CT colonography, and polyps found cannot be removed during the procedure. However, a panel convened by the ACS in 2002 notes that CT colonography may identify cancers located near complex haustral folds and other areas not adequately visualized with conventional colonoscopy (ie, for polypectomy).¹² If proven viable, CT colonography might used to determine which patients require therapeutic colonoscopy.¹² Before it can be adopted for general screening, however, further studies are needed. A large trial comparing CT colonography with optical colonoscopy is now under way.

CERVIX

Medical advances such as liquid-based cytology and human papillomavirus (HPV) testing have prompted significant cervical screening guideline changes within the past few years. According to the ACS, American College of Obstetricians and Gynecologists (ACOG), and USPSTF, an increasing number of women will no longer need annual testing for cervical cancer, and screening can begin later than previously recommended.⁴

Initial screening

The ACS's guidelines for initiating cervical screening—shared by ACOG and USPSTF—state that screening with either a traditional Pap test or liquid-based cytology should begin approximately 3 years after first sexual intercourse or by age 21. ^14,15 Although testing soon after first sexual intercourse or by age 18 had formerly been recommended, the guideline organizations determined that initiating cervical screening within the first several years of vaginal intercourse is unnecessary. Evidence demonstrates that HPV infection in young women is common and often clears within 1 to 2 years without causing cancerous changes. Rather, it is the persistence of HPV as well as the long latency period between initial infection and development of high-grade dysplasia or cervical cancer that causes the problem. Women who have never had intercourse have virtually no risk of developing cervical cancer. The guidelines list an age for initial screening to protect patients who are either unaware of or not forthcoming about prior sexual exposures.

Liquid-based or traditional Pap test?

The traditional Pap test is very effective when done properly, and it is less expensive than liquid-based cytology. No major guideline recommends one test over the other. Although liquid-based tests are considered more sensitive, their specificity is lower than that of Pap tests. They are particularly useful for managing the equivocal Pap test result of atypical squamous cells of undetermined significance (ASCUS): When a Pap test is used, the woman must return for an HPV test. With a liquid-based test, however, resampling the patient is unnecessary before doing an HPV test.

Screening intervals

The ACS and ACOG concur that annual testing for cervical cancer should be conducted until age 30; after age 30, screening can occur every 2 to 3 years for women with 3 negative cytology tests.^4,15 Exceptions to extended screening intervals include women who are either immunocompromised or have a history of cervical intraepithelial neoplasia. The USPSTF recommends that Pap testing be performed at least every 3 years.¹⁴ Among these organizations, only the ACS specifies screening every 2 years rather than annually for women younger than 30 if liquid-based rather than conventional cytology screening is used.⁴ However, ACOG maintains that there are limited data to support this approach and notes that this interval does not take into account potentially false-negative results.¹⁵ Screening intervals for women 30 years and older would change with the use of the HPV test in combination with the Pap test for primary screening.

HPV testing

Several options exist for follow-up of ASCUS Pap test results. One is watchful waiting with follow-up Pap tests every 4 to 6 months. Minor cervical changes may never progress and go away on their own about 50% of the time. The second option is to refer the patient for colposcopy. The third is to perform HPV testing to identify the high-risk HPV types. If the woman is positive for high-risk HPV, she will be referred for colposcopy. About 50% of women with ASCUS will test positive for high-risk types of HPV.¹⁶ If a woman tests negative for a high-risk HPV type, she can be screened with Pap test in 1 year.

The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends "reflex" HPV testing as a convenient and cost-effective approach for follow-up of women of all ages with atypical findings.² The ASCCP also has other recommendations on the use of HPV testing for management of other abnormal cytology or documented CIN (http://www.asccp.org).

As part of routine cervical cancer screening along with the Pap test for women aged 30 and older, HPV DNA testing is now an option for primary cervical cancer screening according to the ACS and ACOG.^4,15 In 2003, the FDA approved the use of the HPV DNA test in conjunction with cervical cytology testing as a cervical cancer screen for women aged 30 and older; it is not, however, approved for use as a stand-alone screening test. The test is only appropriate for women in this age subset. Testing in younger women, therefore, would cause unnecessary anxiety.

Both ACS and ACOG agree on a screening interval of every 3 years for women aged 30 and older with negative test results on concurrent cervical cytology and HPV DNA tests.^4,15 This recommendation is based on evidence that negative combined test results reflect an extremely low risk for developing neoplasia during the next 3 to 5 years. For women who have discordant test results, there has been some interim guidance provided.¹⁶

HPV DNA testing is not indicated for women or men diagnosed with external genital warts or for women or men as a general stand-alone screening test for HPV. This test is also not indicated in general as a follow-up test for women with higher grade cytological results. This is because there is no evidence that it improves clinical management. And for men, test performance is not well-defined.

Before an HPV DNA test is ordered, the clinician must be prepared to provide patient education and counseling, especially regarding HPV test use in the context of cervical cancer screening. Patients must understand some key educational messages about the natural history of HPV and what a positive HPV test result means. Education materials are available at the CDC (http://www.cdc.gov/std/HPV/), ACS (http://www.cancer.org), NCI (http://cis.nci.nih.gov/fact/3_20.htm), and American Social Health Association (http://www.ashastd.org/hpvccrc/hpvmyth.html) Web sites.

Discontinuing cervical screening

Organizations disagree slightly on when to stop cervical screening. If the woman has had a history of 3 normal Pap test results over 10 years, the USPSTF says routine screening should cease by age 65; the ACS, by age 70; and ACOG recommends individualizing the decision based on risk factors for cervical cancer and past screening history.^14,15 All agree that women who have had a complete hysterectomy (with cervix removed) no longer require screening unless the hysterectomy was for cervical cancer or its precursors.

BREAST

With the revision of the USPSTF breast cancer screening guidelines in 2002, the major organizations now agree that mammography should be offered regularly to average-risk women aged 40 and older.^4,17,18 Regardless of when a woman begins a screening regimen, it is important to discuss with her

• The importance of regular screening
• The benefits and limitations of mammography, including the fact that the test will not detect all breast cancers
• False-positive results, which will require additional imaging and maybe even a biopsy, are common, especially in younger women.

Two separate prospective randomized controlled trials have shown strong mortality reductions in women aged 40 to 49 who underwent screening mammography.^19,20 The Two County trial observed twice the rate of interval cancers in younger women compared with older women in the invited group, demonstrating that the detectable preclinical phase was shorter in younger women. Thus it appears the delay in benefit observed in the early trials in women randomized in their 40s is not an overall delay in benefit; rather, it is the outcome of screening every 2 years, which is too infrequent in women with high-grade tumors, and the length of time to observe a statistically significant benefit in women with less aggressive tumors.

Second-generation trials—Malmo and Gothenberg—screened women at 12 to 18 month intervals and showed no delay in benefit. In addition, the trials showed a statistically significant mortality reduction of 36% and 44%, respectively, for women randomized in their 40s. With longer term follow-up, an invitation to screening was associated with a statistically significant reduction in breast cancer mortality in both women aged 40 to 49 and those aged 50 to 69, although the mortality reduction was greater in women older than 50.

That difference in mortality reduction in early randomized controlled trials was most likely due to the wider screening interval, which was less effective in detecting breast cancer early in younger women compared with older women. New large observational studies conducted in Sweden, based on age at the time of diagnosis, show similar mortality reductions for women screened in their 40s to those found in women aged 50 and older when the screening interval is tailored to the age of the woman.²¹

Optimal mammography screening interval

The ACS recommends annual mammography screening starting at age 40 for average-risk women, while the USPSTF recommends every 1 to 2 years because there is no data that annual screening yields greater mortality benefits than biennial screening.^4,17 Given the shorter sojourn time and the greater prevalence of dense glandular tissue in premenopausal women, physicians may consider annual screening to be sensible for women younger than 55.

A recent study of interval cancers in younger women supports this recommendation.²² The investigators found that mammography was 48% sensitive for 2-year follow-up but 72% sensitive when follow-up was limited to 1 year, suggesting that rapid tumor growth in premenopausal women accounted for a higher number of interval cancers and that, therefore, younger women benefit from shorter screening intervals. In postmenopausal women who are not taking hormones, a wider screening interval may suffice; however, as is the case in the younger group, there is no randomized trial data to quantify the difference.

Discontinuing mammography screening

Today, most guidelines recommend individualizing the decision to stop screening based on short life expectancy and comorbid conditions, although estimating a patient's longevity in the absence of any life-limiting comorbidities can be difficult. The average life expectancy for a woman aged 70 years is 15.4 years, and longevity may exceed that in many cases. If a woman older than 70 is in good health and would be a candidate for therapy, the ACS says she should continue to receive screening to reduce the risk of dying from breast cancer.⁴

According to the University of Michigan's Cancer Screening Guidelines, due to the small number of women older than 69 enrolled in the randomized trials on breast cancer screening, there is limited data on the effectiveness of mammography in older women, although other studies of this age-group have shown a benefit from screening by detection of earlier-stage lesions.²³ Alternately, the USPSTF defines an upper boundary based on the age distribution of women who participated in clinical trials, which limits the recommendation to women aged 40 to 70.¹⁷ The USPSTF notes, however, that precise age at which to discontinue mammography is uncertain.

Breast self-examination and clinical breast examination

The USPSTF states that evidence seems insufficient to recommend for or against either breast self-examination (BSE) or clinical breast examination (CBE).¹⁷ The ACS no longer advocates for systematic instruction of BSE nor that women practice monthly BSE; it does not appear to result in significant detection of breast cancer, and most women do not conduct BSE regularly.^4,24 Instead, the ACS suggests that physicians instruct patients to be aware of what is normal for them and to report any abnormality immediately. Women who choose BSE, however, should receive instruction and their technique reviewed.

However, mammography is an imperfect screening tool, especially in women with dense breasts. Therefore, the ACS still favors CBE during physical examinations, as a breast cancer teaching opportunity for women. ACOG concurs that CBE should be conducted annually as part of the physical examination.¹⁸

Advanced screening modalities

For women at significantly increased risk of breast cancer, defined as those with a genetic susceptibility (eg, BRCA1 and/or BRCA2 abnormalities), different modalities such as ultrasound and MRI may be appropriate.⁴ Recent studies have shown productive use of such multimodality imaging in detecting breast cancers in women at very high risk. A comparison of MRI, CBE, and mammography in 1909 high-risk women proved MRI to be significantly more sensitive (79.5%) in detecting invasive breast cancer compared to mammography (33.3%) and CBE (17.9%).²⁵ Similar results were reported in a study of 236 high-risk Canadian women aged 25 to 65 who received a combination of mammography, ultrasound, MRI, and CBE. Of the 22 cancers detected during the study period, 17 (77%) were detected by MRI compared with 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE.²⁶

It is important to note that these gains in sensitivity are somewhat offset by poor specificity; that is to say, both ultrasound and MRI generate a higher rate of false-positive results. In this unique group at appreciably greater risk of breast cancer compared with average-risk women, the higher rate of false-positive results may be an acceptable trade off, although it is important that women at inherited risk who are considering initiating screening at an earlier age learn about the potential benefits and limitations of current surveillance options. This kind of imaging is not recommended for women at average risk or even at increased risk due to more prevalent variants of family history.

Despite the superiority of MRI in high-risk women, a recent clinical review concluded that such new screening modalities are unlikely to replace mammography in the near future for screening the general population.²⁷ MRI has a low positive predictive value and low specificity resulting in many false positives and unnecessary biopsies when used in the general population. Likewise, ultrasound has not been sufficiently evaluated outside the high-risk population. Thus, neither MRI or ultrasound is recommended for general screening.

PROSTATE

Prostate-specific antigen (PSA) testing and DRE may reduce mortality by detecting prostate cancer in its early stages in some patients with moderate-to high-grade tumors. However, the decision to screen for prostate cancer is confounded by the limitations of these tests. A major risk of PSA screening includes treatment with radiation or prostatectomy for a disease that may have remained inconsequential. Also, because PSA testing has poor specificity, false-positive findings occur, leading to unnecessary ultrasound and biopsies.

No major US medical organization endorses universal or mass screening for average-risk men. Given the limitations of the available evidence, the ACS, American Academy of Family Physicians, the American College of Physicians, American Medical Association, and American Urological Association (AUA) recommend that for men aged 50 and older and for men at higher risk for prostate cancer, clinicians

• Discuss with patients the potential benefits and possible harms of PSA testing
• Consider patient preferences
• Individualize the decision to test.^4,28

Those in the high-risk category are African American men and men with a first-degree relative with prostate cancer. These men could consider testing beginning at age 40 or 45, but only after going through a process of informed decision making. The CDC offers "Tools to Facilitate Shared Decision Making for Prostate Cancer Screening" (http://www.cdc.gov/cancer/prostate/screening/toolkit.htm).

DRE: A viable screen?

The AUA states that combining PSA testing and DRE is considered best practice, as this is the most sensitive method for early prostate cancer detection.²⁸ DRE will detect some tumors in patients who have prostate cancer despite a normal PSA (4 ng/mL or less), and, conversely, PSA will detect some abnormalities in patients with normal DRE findings. Furthermore, approximately 20% of aggressive prostate cancers are found in men with PSA levels of less than 4 ng/mL.²⁸

Shared decision making must include a discussion of each test's limitations, such as PSA's poor specificity for prostate cancer and DRE's inaccessibility to areas likely to have cancerous lesions. (Only 25% to 30% of prostate cancers are found in areas accessible by DRE.²⁸) Patient preference should be a strong factor in the decision to conduct either test.

Cutoff value

Although there are no guidelines currently recommending age-specific ranges for PSA cutoff values, many experts consider it in making their decision to proceed to biopsy. Baseline PSA is higher in older men—due to enlarged prostate—than in younger men, although the current guidelines do not address this point. Only the AUA specifies a cutoff value; a PSA value that is 4 ng/mL or more warrants a prostate biopsy.²⁸ Many consider a significant rise in PSA from one test to the next as an indication for the need to perform a biopsy. Cutoff values are receiving increasing scrutiny: New research shows that a cutoff value of 4 ng/mL will miss a significant percentage of occult cancers but that the lower cutoff values will significantly increase the false-positive rate.

When to stop screening

Due to the high prevalence of clinically insignificant prostate cancer in older men, it is recommended that screening stop when life expectancy is less than 10 years.

Drs Smith, Standiford, and Saraiya disclose that they have no financial relationship with any manufacturer in this area of medicine.

REFERENCES

1. Meissner HI, Smith RA, Rimer BK, et al. Promoting cancer screening: learning from experience. Cancer. 2004;101:1107-1117.

2. Breen N, Wagener DK, Brown ML, et al. Progress in cancer screening over a decade: results of cancer screening from the 1987, 1992, and 1998 National Health Interview Surveys. J Natl Cancer Inst. 2001;93:1704-1713.

3. Swan J, Breen N, Coates RJ, et al. Progress in cancer screening practices in the United States: results from the 2000 National Health Interview Survey. Cancer. 2003;97:1528-1540.

4. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2005. CA Cancer J Clin. 2005;55:31-44.

5. Rex DK, Johnson DA, Lieberman DA, et al. Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. Am J Gastroenterol. 2000;95:868-877.

6. US Preventive Services Task Force. Screening for colorectal cancer: recommendations and rationale. Available at: http://www.ahrq.gov/clinic/3rduspstf/colorectal/colorr.htm. Accessed August 4, 2005.

7. Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale–update based on new evidence. Gastroenterology. 2003;124:544-560.

8. Schoenfeld P, Cash B, Flood A, et al. Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med. 2005;352:2061-2068.

9. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. N Engl J Med. 2000;343:162-168.

10. Rex DK, ACG Board of Trustees. American College of Gastroenterology action plan for colorectal cancer prevention. Am J Gastro. 2004;99:574-577.

11. Collins JF, Lieberman DA, Durbin TE, et al. Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice. Ann Intern Med. 2005;142:81-85.

12. Levin B, Brooks D, Smith RA, et al. Emerging technologies in screening for colorectal cancer: CT colonography, immunochemical fecal occult blood tests, and stool screening using molecular markers. CA Cancer J Clin. 2003;53:44-55.

13. Smith R, Cokkinides V, Eyre H. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin. 2003;53:27-43.

14. US Preventive Services Task Force. Screening for cervical cancer. Jan 2003. Available at: http://www.ahcpr.gov/clinic/uspstf/uspscerv.htm. Accessed August 4, 2005.

15. American College of Obstetrics and Gynecology. Cervical cytology screening. ACOG practice bulletin no. 45. ACOG. 2003;102:417-427.

16. Wright TC, Schiffman M, Solomon D, et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gyn. 2004;103:304-309.

17. US Preventive Services Task Force. Screening for breast cancer: recommendations and rationale. Ann Intern Med. 2002;137:344-346.

18. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists. Number 42, April 2003. Breast cancer screening. Obstet Gynecol. 2003;101:821-831.

19. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. BMJ. 1988;297:943-948.

20. Bjurstam N, Bjorneld L, Duffy SW, et al. The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization. Cancer. 1997;80:2091-2099.

21. Tabar L, Vitak B, Chen HH, et al. Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality. Cancer. 2001;91:1724-1731.

22. Buist DS, Porter PL, Lehman C, et al. Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 2004;96: 1432-1440.

23. University of Michigan Cancer Screening Guidelines. Available at: http://cme.med.umich.edu/iCME/cancerscreening04/guideline.asp. Accessed August 4, 2005.

24. Thomas DB, Gao DL, Ray RM, et al. Randomized trial of breast self-examination in Shanghai: final results. J Natl Cancer Inst. 2002;94:1445-1457.

25. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with familial or genetic predisposition. N Engl J Med. 2004;351:427-437.

26. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA. 2004;292:1317-1325.

27. Elmore JG, Armstrong K, Lehman CD, et al. Screening for breast cancer. JAMA. 2005;293:1245-1256.

28. American Urological Association. Prostate-specific antigen (PSA) best practice policy. Available at: http://www.cancernetwork.com/journals/oncology/o0002e.htm. Accessed August 4, 2005.

This article was written by Stacy DiLoreto based on individual interviews with Drs Smith, Standiford, and Saraiya.