Medical Grand Rounds

What’s new in prostate cancer screening and prevention?

Author and Disclosure Information

ABSTRACTProstate cancer is extremely common but causes death in only a minority of men in whom it develops, facts that raise issues regarding screening and treatment morbidity. Two large trials of screening with prostate-specific antigen (PSA) measurements came to seemingly opposite conclusions. Furthermore, a large trial of selenium and vitamin E found that these agents have no value as preventive agents.

KEY POINTS

  • An elevated PSA level lacks specificity as a test for prostate cancer, but PSA measurements can be useful in combination with clinical risk factors or to measure changes in PSA over time.
  • Rather than relying on PSA screening alone, we should stratify the risk of prostate cancer on the basis of race, age, PSA level, family history, findings on digital rectal examination, whether the patient has ever undergone a prostate biopsy, and whether the patient is taking finasteride (Proscar). A simple online tool is available to do this.
  • There is no PSA level below which the risk of cancer is zero.
  • Finasteride has been found in a randomized trial to decrease the risk of prostate cancer, but vitamin E and selenium supplements have failed to show a benefit.


 

References

In spite of some recent studies, or perhaps because of them, we still are unsure about how best to screen for and prevent prostate cancer. Two large trials of screening with prostate-specific antigen (PSA) measurements came to seemingly opposite conclusions.1,2 Furthermore, a large trial of selenium and vitamin E found that these agents have no value as preventive agents.3

See related editorial

Nevertheless, negative studies also advance science, and steady progress is being made in prostate cancer research. In this paper I briefly summarize and comment on some of the recent findings.

TO SCREEN OR NOT TO SCREEN?

All cases of prostate cancer are clinically relevant in that they can cause anxiety or can lead to treatment-related morbidity. The challenge is to detect the minority of cases of cancer that are biologically significant, ie, those that will cause serious illness or death.

Many men have prostate cancer

In the United States, the lifetime probability of developing prostate cancer is 1 in 6, and the probability increases with age. Prostate cancer is primarily a disease of the Western world, but it is becoming more common in other areas as well.

Risk factors for prostate cancer are age, race, and family history. Clinically apparent disease is very rare in men younger than 40 years; until recently, most guidelines suggested that screening for it should begin at age 50. African American men have the highest risk of developing and dying of prostate cancer, for reasons that are not clear. In the past, this finding was attributed to disparities in access and less aggressive therapy in black men, but recent studies suggest the differences persist even in the absence of these factors, suggesting there is a biological difference in cancers between blacks and whites. Having a father or brother who had prostate cancer increases one’s risk twofold (threefold if the father or brother was affected before the age of 60); having a father and a brother with prostate cancer increases one’s risk fourfold, and true hereditary cancer raises the risk fivefold.4

But relatively few men die of it

The Scandinavian Prostate Cancer Group5 randomized 695 men with early prostate cancer (mostly discovered by digital rectal examination or by symptoms) to undergo either radical prostatectomy or a program of watchful waiting. In 8.2 years of follow-up, 8.6% of the men in the surgery group and 14.4% of those in the watchful waiting group died of prostate cancer. Thus, we can conclude that surgery is beneficial in this situation.

Adapated from Bill-Axelson A, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005; 352:1977–1984. Copyright 2005 Massachusetts Medical Society. All rights reserved.
Figure 1. The natural history of prostate cancer, as shown by data from the Scandinavian Prostate Cancer Group.5 Most men who have prostate cancer could probably avoid treatment, but it is hard to tell which ones.
But there is a more important and subtle message. A small percentage of men with prostate cancer (about 6% in this study) benefit from treatment. More (8.6% in this study) die of prostate cancer despite curative treatment. But most men with prostate cancer could avoid therapy—about 85% in this study, and likely more in men with prostate cancer detected by PSA testing (Figure 1). According to data from a recent European study of PSA screening,2 one would have to screen about 1,400 men and do about 50 prostatectomies to prevent one death from prostate cancer.

Despite these calculations, in contemporary practice in the United States, about 90% of men with newly diagnosed low-grade prostate cancer choose to be treated.6 This high level of intervention reflects our current inability to predict which cancers will remain indolent vs which will progress and the lack of validated markers that tell us when to intervene in patients who are managed expectantly and not lose the chance for cure. Most often, patients and their physicians, who are paid to intervene, deal with this uncertainty by choosing the high likelihood of cure with early intervention despite treatment-related morbidity.

What PSA has wrought

When PSA screening was introduced in the late 1980s and early 1990s, it brought about several changes in the epidemiology and clinical profile of this disease that led us to believe that it was making a meaningful difference.

A spike in the apparent incidence of prostate cancer occurred in the late 1980s and early 1990s with the introduction of PSA screening. The spike was temporary, representing detection of preexisting cases. Now, the incidence may have leveled off.7

A shift in the stages of cancers detected. In 1982, half of men with newly diagnosed prostate cancer had incurable disease.8 Five years after the introduction of PSA testing, 95% had curable disease.9

An increase in the rate of cure after radical prostatectomy was seen.

A decrease in the death rate from prostate cancer since the early 1990s has been noted, which is likely due not only to earlier detection but also to earlier and better treatment.

Pages

Next Article:

Generalized pruritus after a beach vacation

Related Articles