Burden of Suffering
Prostate cancer is the most commonly diagnosed cancer in the United States (excluding skin cancers) and is second only to lung cancer as a contributor to cancer deaths in American men. In 1997, an estimated 209,900 new cases will be diagnosed and 41,800 men will die of prostate cancer. (1,2) One in every five U.S. men will develop invasive prostate cancer before their death. Age-adjusted incidence of prostate cancer has been increasing over the last 50 years, with a sharper rise over the past decade associated mostly with increasing early detection. Disease-specific 5-year survival rates among white men are 100% when the cancer is localized, 94% for those with regional disease, and 31% for those with distant metastasis. (1) Genetic, environmental, and social risk factors have been identified for prostate carcinoma including familial, dietary, hormonal, and possibly environmental carcinogen influences. (3) Incidence increases with age and those with a family history or African-American men are at higher risk of both developing and dying from prostate cancer.
Benign prostatic hyperplasia, another common disorder of older males characterized by an enlarged prostate gland, has not been directly linked to prostate cancer , although both are associated with advancing age and androgen metabolism. (4) An unknown fraction of prostate cancers are clinically insignificant. Prostate cancer is characterized by a wide variability in rates of disease progression and long preclinical asymptomatic phases. Many men die with prostate cancer not because of it.
Description of the Preventive Measures
The principal screening tests for detection of asymptomatic prostate cancer are the digital rectal examination (DRE) and measurement of the serum tumor marker prostate specific antigen (PSA). Transrectal ultrasound is no longer considered a first-line screening test for prostate cancer, but does play a role in the investigation of patients with abnormal DRE or PSA.
Evidence of Effectiveness
Both DRE and PSA can detect occult prostate cancer. Reported values for the sensitivity, specificity, and positive predictive value of DRE and PSA may not reflect true values; however, because the number of false-negative cases is often unknown, studies traditionally screen volunteers, whose cancer risk may differ from the general population, and fine-needle biopsies may miss cancerous lesions. DRE has a reported sensitivity of 55%-68% in asymptomatic men, (5,6) but values as low as 18%-22% have been reported. (7,8) The reported positive predictive value of DRE is 6%-33%. (6,9)
A PSA of greater than 4.0 ng/ml, the accepted threshold for further diagnostic evaluation, has been reported to be over 80% sensitive in detecting prostate cancer, although some studies report a much lower sensitivity of 29%. (7) PSA appears to have increased sensitivity for aggressive cancers (10) and those with histopathologic features associated with progression: large volume, poorly differentiated cells, extracapsular penetration. (11-14) PSA has limited specificity because elevations also occur in men with benign disease (e.g., prostatic hypertrophy, prostatitis). The reported positive predictive value of PSA in asymptomatic men is 28%-35%. (6,13,15, 16) The specificity and/or positive predictive value of PSA may be enhanced by measuring PSA density (PSA value divided by gland volume measured by transrectal ultrasound), (17) PSA velocity (annual rate of change of PSA), (18) the free PSA ratio, (19-23) age -adjusted PSA reference ranges, (24,25) or increasing the cut-off value. Combining PSA with DRE increases the positive predictive value to 49%. (6)
There is no direct evidence whether or not early detection and treatment of prostate cancer reduces mortality because randomized clinical trials to address this question have not been completed. Observational studies of DRE report no improvement in mortality, (26, 27) but the designs of these studies have been challenged. Screening does detect cancers at an earlier stage, (13,28) which is theorized (but unproven) to improve survival. The incidence of metastatic disease decreases over time in settings where screening occurs. (29) However, these findings are of uncertain significance. They may be complicated by lead time or length-time biases and by alterations in the effectiveness of treatments. Because screening may be detecting cancers that would never have caused morbidity or mortality in the host, the value of early detection remains unclear.
The effectiveness of treatment for prostate cancer is also uncertain. Well-designed randomized controlled trials of surgery, radiation, and other treatment modalities have not been completed. Observational studies suggest that, for localized and moderately or well-differentiated cancers, observation ("watchful waiting") may be as beneficial as treatment in men followed for over 12 years. (30-33) It is clear that men with a life expectancy of less than 10 years rarely benefit from radical prostatectomy.
Both screening and treatment can be harmful. A positive DRE and/or PSA requires repeat testing and can lead to more invasive diagnostic tests, such as needle biopsy, which carries a small risk of infection, sepsis, or bleeding and may be performed on 18% of the screened population. (6) Radical prostatectomy and radiation therapy can produce serious complications affecting quality of life such as urinary incontinence, erectile dysfunction, or strictures and, rarely, can be fatal. Decision analyses weighing the benefits and risks suggest that one-time screening produces a modest gain measured in days to months, or a net loss in quality-adjusted life expectancy, (34-36) results vary depending on the cohort's age, and other assumptions. Little is known about the individual psychological burden involved in prostate cancer screening and decision-making regarding treatment .
Public Policy Considerations
Observational studies report variable rates of compliance with screening recommendations and official recommendations, even if tests are "free." (9) In one longitudinal study of male volunteers, at 4 years 79% of men returned for P.A. screening. (37) Another population - based study in France invited men to either P.A. or DRE-transrectal ultrasound screening (TRUS) and reported 33.7% attendance at DRE-TRUS screening and 66.9% attendance at P.A. screening. (38) Understanding of prostate cancer screening may be low among the general population; one study found poor knowledge about P.A. testing (e.g., more than half had never heard of the test) among men 2 weeks after they had undergone P.A. testing. (39) In addition, primary care providers may not have adequate knowledge about the correct use of DRE and P.A.. One survey reported that 59% of primary care respondents did not know whether DRE or P.A. was more sensitive, and 45% agreed that all patients with P.A. >4.0 ng/ml had cancer. (40) Inadequate knowledge among primary care providers and patients may cause difficulty in obtaining adequateinformed consent. Few studies have addressed which types of materials are optimal for informed consent, although one study found that in their population of men lower socioeconomic status, informed consent was associated with decreased interest in PSA screening. (41)
Prostate cancer screening is likely to be expensive; it has been estimated that the first year of mass screening would likely cost between $12 billion and $28 billion , (7, 42) with costs increasing as the U.S. population ages. Without solid evidence on the effectiveness of prostate cancer screening in reducing mortality and morbidity, cost-effectiveness cannot be properly calculated. Controlled studies of PSA screening may encounter problems with patient recruitment because of the increasing use of PSA screening in the general population. It is unclear whether PSA screening results will affect insurance eligibility. Recommendations regarding screening tests are often used as the basis for insurance decisions regarding whether to cover those tests.
Recommendations of Other Groups
The American Urological Association and the American College of Radiology recommend annual DRE and PSA screening beginning at age 50 and annual PSA screening beginning at age 40 for African-American men and other men with a positive family history of prostate cancer. The American Cancer Society recommends these tests be offered annually to men who are age 50 and over, who have at least a 10-year life expectancy; annual screening is offered earlier for African-American men or those with at least two first -degree relatives affected. The American College of Physicians and Office of Technology Assessment recommend giving men information about the benefits and harms of screening to help them make a decision based on personal preferences. The U.S. Preventive Services Task Force and the Canadian Task Force on the Periodic Health Examination recommended against the routine screening (the Canadian Task Force found insufficient evidence to make a recommendation on DRE). Technology assessment agencies in Canada, England, Sweden, and Australia have recommended against routine population screening for prostate cancer.
Rationale Statement
Prostate cancer is a significant and growing cause of morbidity among U.S. men and is not amenable to primary prevention. Screening can detect prostate cancer early, and early detection has the potential to decrease both morbidity and mortality, but these benefits are unproven and may not be realized because of the characteristics of this disease (e.g., prevalence of latent clinically insignificant prostate cancer, indolent growth rate, and treatment-associated morbidity). For now, there is no convincing evidence that early detection and treatment improve outcomes. When cancers are well or moderately differentiated, expectant management may be as effective as surgery and only palliation is possible for cancers that have spread beyond the prostatic capsule. While early detection of some tumors may translate into decreased mortality, it is difficult to predict definitively which men will die of prostate cancer and which will die with it. Widespread screening may burden a large number of men with both psychological and physical complications, which may offset potential benefits. Since the best option depends on personal preferences, men considering PSA screening deserve information about the potential benefits and harms of available options and the quality of the supporting evidence.
Recommendation of the American College of Preventive Medicine
The American College of Preventive Medicine recommends against routine population screening with DRE and PSA. Men age 50 or older with a life expectancy of greater than 10 years should be given information about the potential benefits and harms of screening and limits of current evidence and should be allowed to make their own choice about screening, in consultation with their physician, based on personal preferences. Methods and tools for helping patients review this information are available; (41,43) however, the ACPM recommends further research be conducted in optimizing the process of patient education and informed consent.
References
2. Wingo PA, Landis S. Ries L.A. An adjustment to the 1997
estimate for new Prostate cancer cases. CA Cancer J Clin 1997;47:239-42.
3. Haas GP Sakr WA. Epidemiology of Prostate Cancer.
Cancer J Clin 1997;47:273-8.
4. Boyle P. New Insights in the epidemiology and natural
history of benign prostatic hyperplasia. Prog Clin Biol Res 1994;386:3-18.
5. Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate specific antigen
in serum as a screening test for prostate cancer. NEJM 1991;1156-61.
6. Catalona WJ, Richie JP, Ahmann FR, et al. Comparison of digital rectal examination
and serum prostate specific antigen in the early detection of prostate cancer: results
of a multi-center clinical trial of 6,630 men. J Ural 1994A;151:1283-90.
7. Optenberg SA, Thompson IM. Economics of screening for carcinoma of the
prostate. Ural Clin North Am 1990;17:719-37.
8. Vihko P, Kontturi O, Ervast J, et al. Screening for carcinoma of the prostate: rectal
examination and enzymatic radioimmunologic measurements of serum acid phosphatase
compared. Cancer 1985;56:173-7.
9. Chodak GW, Keller P, Schoenburg HW. Assessment of screening for prostate cancer using
the digital rectal examination. J Ural 1989;141:1136-8.
10. Gann PH, Hennekens CH, Stampfer MJ. A prospective evaluation of plasma prostate-specific
antigen for detection of prostate cancer. JAMA 1995;263:289-94.
11. Mettlin C. Mruphy GP, Lee F, et al. Characteristics of prostate cancer detected in the
American Cancer Society National Prostate Cancer Detection Project. J Ural 1994;
152:1737-40.
12. Scaletscky R. Koch MO, Eckstein CW , et al. Tumor volume and stage in carcinoma of
the prostate detected by elevations in prostate specific antigen. J Ural 1994;152:129-31.
13. Catalona WJ, Smith DS, Ratliff TL, Basler JW. Detection of organ-confined prostate cancer
is increased through use of prostate-specific antigen-based screening. JAMA 1993;270:948.
14. Humphrey PA, Keetch CW, Smith DS, Catalona WJ. Prospective characterization of
pathologic features of prostate carcinomas detected via serum prostate specific antigen
based screening. J Urol 1996;155:816-20.
15. Cooner WH, Mosley p, Rutherford CL Jr., et al. Prostate cancer detectin in a clinical
urological practice by ultrasonography, digital rectal examination and prostate specific
antigen. J Urol 1990;143:1146-52.
16. petton PR. Prostate specific antigen and digital rectal examination in screening for prostate
cancer: a community-based study. South Med J 1994;87:720-3.
17. Benson MC, Whang IS, Pantuck A, et al. Prostatic specific antigen density: a means of
distinguishing benign prostatic hypertrophy and prostate cancer. J Urol 1992;1476:815-16.
18. Carter HB, Pearson JD, Metter PJ., et al. Longitudinal evaluation of prostate-specific
antigen levels in men with and without prostate disease. JAMA 1992;267:2215-20.
19. Reissigl A, Klocker H, Pointner J, et al. Usefulness of the ratio of free total prostate
specific antigen in addition to total PSA levels in prostate cancer screening. Urology
1996;48:62-6.
20. Morgan TO, McLeod DG, Leifer ES, et al. Prospective use of free prostate-specific antigen
to avoid repeat biopsies in men with elevated total prostate specific antigen. Urology
1996;48:76-80.
21. Higashihara E, Nutahara K, Kojima M, et al. Significance of serum free prostate specific
antigen in the screening of prostate cancer. J Urol 1996;156:1964-8.
22. Murphy GP, Natarajan N, Pontes JE, et al. Evaluation and comparison of two new prostate
carcinoma markers. Cancer 1996;78;809-18.
23. Catalona WJ, Smith DS, Ornstein DK. Prostate cancer detection in men with serum PSA
concentrations of 2.6-4.0 nh/mL and benign prostate examination: enhancement of spec-
ificity with serum free PSA measurements. JAMA 1997;277:1452-5.
24. Osterling JE, Jacobsen SJ, Chute CG, et al. Serum prostate specific antigen in a
community -based population of healthy men: establishment of age-specific reference
ranges. JAMA 1993;270:860-4.
25. Catalona WJ, Hudson MA, Scardino PT, et al. Selection of optimal prostate cancer:
receiver operating characteristic curves. J Urol 1994B;152:2037-42.
26. Gerber GS, Thompson IM, Thisted R, Chodak GW. Disease-specific survival following
routine prostate cancer screening by digital rectal examination. JAMA 1993;269:61-4.
27. Friedman GD, Hiatt RA, Quesenberry CP, Selby JV. Case-control study of screening for
prostatic cancer by digital rectal examinations. Lancet 1991;337:1526-9.
28. Gilliland FD, Hunt WC, Key CR. Improving survival for patients with prostate cancer
diagnosed in the prostate-specific antigen era. Urology 1996;48:67-71.
29. Lapie F. Candas B, Cusan L, et al. Diagnosis of advanced or noncurable prostate
cancer can be practically eliminated by prostate-specific antigen. Urology 1996;47:212-17.
30. Adolfsson J. Deferred treatment of low grade stage T3 prostate cancer without distant
metastasis. J Urol 1993;149:326-9.
31. Warner J, Whitmore WF Jr. Expectant management of clinically localized prostate cancer.
J Urol 1994;152:1757-60.
32. Chodak GW, Thisted RA, Gerber GS, et al. Results of converative management of
clinically localized prostate cancer. N Engl J Med 1994;330:242-8.
33. Johansson JE, Holmberg L, Johansson S, et al. Fifteen-year survival in prostate
cancer: a prospective population-based trail in Sweden. JAMA 1997;277:467-71.
34. Cantor SB, Spann SJ, Volk RJ, et al. Prostate cancer screening: a decision analysis.
J Fam Pract 1995; 41:33-41.
35. Krahn MD, Mahoney JE, Eckman JE, Eckman MH, et al. Screening for prostate cancer:
a decision-analytic view. JAMA 1994;262:773-80.
36. Coley CM, Barry MJ, Fleming C, et al. Early detection of prostate cancer. Part II.
Estimating the risks, benefits and costs. Ann Int Med 1997;126:468-79.
37. Smith DS, Catalona WJ, Herschman JD, Longitudinal screening for prostate cancer
with prostate-specific antigen. JAMA 1996;1309-15.
38. Giatto S, Bonardi R, Mazzotta A, et al. Comparing two modalities for screening for
prostate cancer: digital rectal exam plus trans rectal ultrasound versus prostate-specific
antigen. Tumor 1995;81:225-9.
39. Diefenbach PN, Ganz PA, Pawlow AJ, Guthrie D. Screening by the prostate-specific
antigen test: what do patients know? J Cancer Educ 1996;11:39-44.
40. Plawker MW, Fleisher JM, Nitti VW, Macchia RJ. Primary care practitioners:
an analysis of their perceptions of voiding dysfunction and prostate cancer. J Urol
1996;155:601-4.
41. Wolf AMD, Nasser JF, Wolf AM, Schorling JB. The impact of informed consent on
patient interest in prostate-specific antigen screening. Arch Intern Med 1996;156: 1333-6.
42. Kramer BS, pown ML, Prorok PC, et al. Prostate cancer screening: what we know and
what we need to know. Ann Intern Med 1993;119:914-23.
43. Flood AB, Wennberg JE, Nease RF, et al. The importance of patient preferences in the
decision to screen for prostate cancer. J Gen Intern Med 1996;11:342-9.
1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics
1997 CA Cancer J Clin 1997;47:5-27
Screening Asymptomatic Women for Ovarian Cancer
Skin Protection from Ultraviolet Light Exposure
Screening Mammography for Breast Cancer
Strengthening Motor Vehicle Occupant Protection Laws
Tobacco-Cessation Patient Counseling