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Re: Screening for Prostate Cancer
Submit responseWe appreciate the letters from Drs. Konety and Gogol regarding the U.S. Preventive Service Task Force’s (USPSTF) updated recommendation on screening for prostate cancer. (1) The USPSTF recommended against screening men age 75 years and older.
It is important to emphasize first that a systematic review conducted in collaboration with the USPSTF (2) identified no direct evidence (i.e. evidence from randomized trials) that permitted the USPSTF to determine whether prostate-specific antigen (PSA) screening has a net benefit on mortality for men of any age. While some men may benefit from earlier detection of potentially fatal prostate cancers, others will be harmed by the adverse effects of detection and treatment of abnormal-appearing prostate cells that would never have caused clinical symptoms. We will not know if the uncontrolled experiment of screening millions of men for prostate cancer that began in the early 1990s has, on the whole, increased life-expectancy or shortened it until ongoing randomized trials are completed.
In concluding with moderate certainty that the harms of screening men age 75 years and older outweigh the benefits, the USPSTF relied on information about the natural history of clinically-detected prostate cancer from a randomized trial comparing the outcomes of radical prostatectomy and watchful waiting. (3) This trial suggested that the length of time required to experience a mortality benefit from PSA screening is greater than ten years. Even assuming that every prostate cancer detected by screening is potentially fatal (not true) and that treatments are never fatal (also not true), the majority of men age 75 years and older would experience no benefits from screening.
Recently published data from the Bill-Axelson trial (4) suggests that the USPSTF may have set the screening “cutoff” age conservatively. Men in the trial over age 65 years who underwent prostatectomy had the same mortality rate as men who did not. (4)
Dr. Konety asserts that older men diagnosed with “low risk” prostate cancer could choose to enter active surveillance rather than undergo treatment, thus reducing the harms associated with prostate cancer screening. In practice, potentially lethal prostate cancers cannot be reliably identified. Because of the desire of most men to remove all traces of cancer, attrition rates from studies of active surveillance have been high, rendering the effectiveness of the surveillance protocol uninterpretable. (2) In addition, there is no evidence that active surveillance itself leads to more benefits than harms.
References
1. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:185-191.
2. Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 2008;149:192-199.
3. Bill-Axelson A, Holmberg L, Ruutu M, Haggman M, Andersson SO, Bratell S, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005;352:1977-1984.
4. Bill-Axelson A, Holmberg L, Filen F, Ruutu M, Garmo H, Busch C, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100:1144 -1154.
Conflict of Interest:
None declared
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A more nuanced approach to prostate cancer screening
Submit responseTo the Editor:The USPSTF authors again tackle a difficult subject in updating their recommendations for prostate cancer screening. The most significant change in the new guideline is the grade D recommendation against screening men over the age of 75 years, based on a perceived lack of benefit for prostate cancer treatment in these older men. We would argue, however, that rather than adopting rigid age-based stopping criteria for screening, the medical community should pursue a more nuanced approach to screening, diagnosis, and treatment across age strata.
Screening and potential overdiagnosis of prostate cancer are primarily concerning to the extent that they lead to overtreatment. Overtreatment is certainly a substantial problem among men with low risk prostate cancer, particularly among older men.[1] With cessation of screening among older patients, however, we lose the opportunity to detect aggressive prostate cancer among patients who are in fact most likely to have it. The incidence of high risk prostate cancer in fact increases with age, accounting for 42% of cancers diagnosed in men >75 years vs. 22% among men <75 years.[2] Indeed, as much as overtreatment of low risk disease remains a concern, we have also found evidence of growing underuse of potentially curative local therapy among the men with high risk disease who face the highest risk of disease-specific morbidity and mortality.[3] Rigid age-based criteria, moreover, ignore substantial variation in life expectancy based on overall health and comorbid illnesses.
We have previously attempted to develop multi-specialty consensus recommendations aimed at encouraging a more cautious approach to screening for prostate cancer in men >75 years. During these discussions primary care physicians expressed significant interest in continued screening even in older men and were reluctant to stop screening at a predetermined age. After a yearlong educational campaign, stated physician preferences for continued screening beyond 75 years fell 20%. However the demographic correlates of screeners vs non-screeners did not change: screeners were more likely to be older men themselves.[4]
All patients with mildly elevated PSA on screening tests do not necessarily require further diagnostic evaluation. Likewise, many older men—likely a substantial majority—diagnosed with lower risk tumors can be safely followed with active surveillance.[5] Indeed, a greater onus must be placed on physicians (and the men they counsel) to divorce diagnosis from inevitable treatment. Those older men harboring undiagnosed aggressive tumors, however, risk substantial potential morbidity and potential mortality from progressive disease, and should not be denied the opportunity for treatment.
References:
1. Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR: The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol 2004; 22: 2141.
2. Konety BR, Cowan JE, Carroll PR; CaPSURE Investigators. Patterns of primary and secondary therapy for prostate cancer in elderly men: analysis of data from CaPSURE. J Urol. 2008;179:1797-804.
3. Cooperberg MR, Cowan J, Broering JM, Carroll PR: High-risk prostate cancer in the United States, 1990-2007. World J Urol 2008; 26: 211.
4. Konety BR, Sharp VJ, Raut H, Williams RD. Screening and management of prostate cancer in elderly men: the Iowa Prostate Cancer Consensus. Urology. 2008;71:511-514.
5. Dall'Era MA, Konety BR, Cowan JE, Shinohara K, Stauf F, Cooperberg MR, Meng MV, Kane CJ, Perez N, Master VA, Carroll PR. Active surveillance for the management of prostate cancer in a contemporary cohort. Cancer 2008;112:2664-2670.
Conflict of Interest:
None declared
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Age cut-offs alone are misleading
Submit responseThe authors define an age cut-off for prostate cancer screening negating this screening for men at age greater 75 years (y) or a life expectancy below 10 y (1). It may be uncertain if screening for prostate cancer using prostate-specific antigen is a useful tool irrespective of age. But an age cut-off of 75 y may be wrong for some men aged 75 y and higher. As Walter and Covinsky (2) reported was the life expectancy for U.S. men in 1997 at age 75 for the top 25th percentile 14,2 y, at age 80 10,8 y and at age 85 7,9 y. For the same age groups the top 50th percentile was 9,3, 6,7 and 4,7 y. In an ageing world (3) it is necessary for clinicians, health care providers and political decision makers to have in mind that aging is different in people with variuos health and functional status. The “best agers” will have a life expectancy of 4.3 y in men and 4.8 y in women (top 25th percentile) at age 95. Summing up biological age alone is a bad adviser for decision making. 1. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:185-91. 2. Walter LC, Covinsky KE. Cancer screening in elderly patients. A framework for individualized decision making. JAMA 2001;285:2570-6. 3. Lutz W, Sanderson W, Scherbov S. The coming acceleration of global population aging. Nature 2008;451:716-9. Conflict of Interest:None declared