On October 11, the U.S. Preventive Services Task Force (USPSTF) issued a draft of updated recommendations relating to screening for prostate cancer with PSA, in which they made a recommendation not to screen for prostate cancer using PSA (grade D recommendations, moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits).  This represents a change from their previous recommendations, which only recommended against screening in men over age 75.  Other organizations have made recommendations that differ from these.  Several, notably the American Cancer Society (ACS) and American College of Physicians (ACP), recommend that decisions on screening be based on discussions between an individual and their physician about the risks and benefits of detecting prostate cancer early.  The American Urological Association (AUA) recommends routine screening for prostate cancer using PSA, as do many public awareness programs.  

Prostate cancer is the most common internal cancer in men, and the second most common cause of cancer death.  Autopsy studies done before screening became widespread found that prostate cancer was extremely common as men aged; 75% of men in their 80’s had prostate cancer. In a landmark study in Scandinavia, 223 men with early prostate cancer (mostly in their 60’s and 70’s at diagnosis) were followed for 21 years without treatment. At the end of that time, only 9% of the men were still alive. Most of the prostate cancers caused little harm during the first 10-15 years after diagnosis, but became progressively more widespread after that time in the 49 men who were still alive. This study pointed out the slow progression of prostate cancer, and the need for long follow-up to show any benefits from detecting prostate cancer early. Only 35 men died of prostate cancer, while 168 died of other causes. (1)

Over the past 20 years, prostate specific antigen (PSA), an enzyme produced by the prostate, has been widely used as a screening test for prostate cancer. Its use was based on a relatively high sensitivity for detecting prostate cancer localized to the prostate (about 60% using a cutoff of 4 ng/mL), and the belief that treatment of prostate cancer detected at an early stage would lead to reduced deaths from prostate cancer and, thus, reduced overall mortality. A major concern with screening is that, as pointed out by the Scandinavian study, this slow-growing cancer occurs in older men, who are often likely to die of other causes. Treatment for prostate cancer is associated with death in a small number of men, and significant complications (loss of ability to control bowel and bladder, recurrent infections, erectile dysfunction) are common, occurring in up to 40% of men.

Over the past few years, a number of studies have looked at whether screening with PSA (or early treatment of prostate cancer) actually achieves these desired outcomes. Two large studies of screening for prostate cancer with PSA were reported on in the New England Journal of Medicine in 2009. The first, from the United States, involved over 75,000 men randomly assigned to have screening for prostate cancer or usual care. After 7-10 years of follow-up, prostate cancer was diagnosed more commonly in the group assigned to screening, but deaths were not significantly different between the two groups and death from prostate cancer was rare (2). This study has been criticized because over half of men not assigned to screening actually had PSA and rectal examination performed. The second study, from Europe, involved 182,000 men randomly assigned to screening or usual care. Few men in the usual care group actually did undergo screening, answering the major criticism of the US study. Over 8 years of follow-up, prostate cancer was diagnosed almost twice as frequently in those screened (8.2% versus 4.8%), and deaths from prostate cancer were less common in the screened group (relative risk 0.80, confidence interval 0.65-0.98). The authors estimated that 1410 men would have to be screened and 48 treated for prostate cancer to prevent one death (3). Finally, one study looked at treatment of prostate cancer in 695 men randomly assigned to radical surgery or watchful waiting (no surgery, treatment only if disease progressed). In this Scandinavian study, follow-up through a mean of 10.8 years, total mortality did not differ between the two groups. However, death from prostate cancer and presence of distant metastases were significantly more likely in the group assigned to watchful waiting (4). It is important to note that the average follow-up time was less than 11 years in all of these studies, while the study in untreated prostate cancer showed that problems tended to become more widespread after 15 years of follow-up.

This is the data on which differing organizations have made different recommendations. The American Cancer Society has estimated that, of those screened and diagnosed with prostate cancer, over 80% will elect to have definitive treatment. While data suggest that this will reduce deaths from prostate cancer, it does so at the risk of significant, life altering complications and probably does not reduce overall mortality. In a recent survey by US News and World Report, most doctors will still recommend PSA screening for their patients despite the lack of evidence. It is probably reasonable, before agreeing to screening, for men to be aware of the data that has been published, and the uncertainty about the benefits of screening and risk of complications, before making a decision on whether to be screened. I personally have made a decision not to be screened using PSA.

References

  1. Johansson J-E, Andrén O, Andersson S-O, Dickman PW, Holmberg L, Magnuson A, et al. Natural History of Early, Localized Prostate Cancer. JAMA: The Journal of the American Medical Association 2004;291:2713-2719.
  2. Andriole GL, Crawford ED, Grubb RL, Buys SS, Chia D, Church TR, et al. Mortality Results from a Randomized Prostate-Cancer Screening Trial. New England Journal of Medicine 2009;360:1310-1319.
  3. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, et al. Screening and Prostate-Cancer Mortality in a Randomized European Study. New England Journal of Medicine 2009;360:1320-1328.
  4. Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, et al. Radical Prostatectomy Versus Watchful Waiting in Localized Prostate Cancer: the Scandinavian Prostate Cancer Group-4 Randomized Trial. Journal of the National Cancer Institute 2008;100:1144-1154.