PSA Screening for Prostate Cancer

By Marcus M. Reidenberg, MD, FACP
Weill Cornell CERT

The recent recommendation for deciding whether or not to screen men for prostate cancer is for the doctor and patient to share the decision. This decision should be made after a full discussion of the harms and benefits of screening with the doctor taking into account the personal preferences of the patient (1-3). What a wonderful idea but barely possible in practice for most men in the U.S. today. In fact, a study showed that this was rarely being done (4). The reason is the very low insurance reimbursement rates for time spent seriously discussing matters with patients. Here is some information about this complex disease that may explain some of the issues and help some men faced with making a decision about having a PSA test.

Cancer cells develop in the prostate in most men as they age but cause no trouble for most of them. Autopsy studies of men who died of other causes show that 30% of men above the age of 50 and 70% of men over the age of 70 had nests of prostate cancer cells in their prostate glands. These prostate cancers were too small to be detected by biopsy and gave the men no trouble for their whole lives (5). How many men do get trouble from their prostate cancers? The statistics show that of the 1,203,968 men who died in the U.S. in 2007, 2.4% of them died from prostate cancer. While prostate cancer is the second most common cause of cancer death in men, its 2.4% of deaths compares to 32% who died of cardiovascular disease and 22% who died from cancers of other organs.

Men with 2 blood relatives who died of prostate cancer are in a high risk group with a risk 3-5 times higher for this cancer than men who have no relatives who died of prostate cancer. African-American men get prostate cancer at about double the rate of men of European ancestry and die from it at double the rate also. Why they get more prostate cancers and why they die more often from them is not understood at this time. Asian-American men get prostate cancer less frequently than men of European ancestry (6-8). Men with no relatives who died of this disease and are not of African ancestry are the low risk group. Men with one of these risk factors, a blood relative who died of prostate cancer or have African ancestry are in an intermediate risk group. Thus the two factors that increase the risk of a man’s getting prostate cancer are prostate cancer in the family and African ancestry.

How good is PSA screening to lower the death rate from prostate cancer? Here are some estimates from a review (7). This table shows the number of men per 1,000 who will have died before age 85 from prostate cancer or from other causes.

 

Low Risk Men
Died From Prostate Cancer
Died From Other Causes
Total
Unscreened
30
611
641
Screened
28
612
640
High Risk Men
Unscreened
137
570
707
Screened
129
575
704

 

Thus many men screened still die of their prostate cancer despite screening.

Many men in the screened group will have abnormal PSA tests and prostate biopsies. Many of the biopsies will not show cancer. Thus the PSA test was a false positive test. Over 10 years, up to 20% of low risk men will have positive PSA tests with negative biopsies showing these were false positive tests. This is because PSA is prostate-specific, not prostate cancer-specific, i.e., other things in the prostate can raise the PSA. Men in the higher risk groups will have even more false positive tests. They will also have more true positive tests than men in the low risk group.

A weakness with this table is that the data for unscreened men was taken from population data from Australia between 1982-1988 before screening was implemented in Australia. The data from screened men came from the screened group in a randomized trial of screening. There are several assumptions made to calculate these estimates of long term benefit and harm from data collected over a few years’ time period that are probably not absolutely true in real life. But they are reasonable enough to use these numbers as a guide for the effect of PSA screening. But the absolute numbers are rough estimates, not accurate figures. They must be thought of as such.

The other statistics in this Note and in other reviews or articles about PSA screening are from trials in which one group was randomized to “customary care” and the other group to annual PSA tests. This does not mean that members of the customary care group never had a PSA test. It is likely that some of these men had such tests as part of their routine medical care. If these PSA tests picked up some very early cancers, these early-detected cancers in the customary care group would make the screening programs appear less effective than if the screened men were compared to never tested men. The reason is that if some of the customary care group had cancers detected early by the PSA while in an “never tested” group these cancers grow until they were clinically detectable and perhaps less likely to be cured by therapy. Another weakness is the relatively short time period of the randomized studies. Prostate cancer is a very slowly growing cancer. Those tumors that grow and metastasize usually do so at a rate measured in many years or even decades. A follow up period of 13 years, the longest period of follow up so far, is too short to know the full benefits of screening. And since many men live well past age 85, the estimations in the table to age 85 cannot be used to assess the effects of screening beyond age 85. Detecting and treating prostate cancer at a younger age may keep men who would have died of prostate cancer at a younger age alive past age 85. We just don’t know the statistics.

Prostate biopsy is not harmless. Sometimes there is pain. Bleeding or infection can occur afterwards. There is always time, inconvenience, and expense, and worry until the outcome is known. Treatment of prostate cancer can cause erectile dysfunction, urinary incontinence, and, rarely, bowel dysfunction. Thus different people value the ratio of benefit to harm differently. All screening guidelines agree however that a man needs a life expectancy of 10 years or more for there to be any potential benefit from screening. The reason is that it takes around 10 years for a cancer so small to be detected only by PSA screening to grow enough to cause real trouble. This is similar to the time needed for a polyp of the colon to become a troublesome cancer. Usually, PSA testing is suggested as part of an annual check up while the recommended interval between colonoscopy screening tests for colon cancer is no more often than every 5 years (9). It is reasonable to question this difference in time intervals.

Nests of prostate cancer cells have been found in men with low PSA levels. In a study of normal men who had biopsies irrespective of PSA levels, 15% with PSA below 4 ng/ml had positive biopsies and 9% with PSA below 1 ng/ml had positive biopsies (5). Proper interpretation of the biopsy and skilled clinical assessment of the patient is critical in determining the appropriate course of action.

At this time, there is no way to know for certain if a tiny cancer found at PSA screening followed by a biopsy will develop into a problem for the man or not. Many patients who are currently diagnosed as having prostate cancer may not require active treatment at the time of initial diagnosis. They are likely to be candidates for “active surveillance” where follow-up PSAs and subsequent biopsies are done. Such an approach has the potential to limit the risk of side effects of local treatment, with the intention that prostate cancer growth can be detected and treated when necessary. At least 30-50% of patients who begin active surveillance will subsequently have radiation or surgical treatment.

The most recent study of regular screening compared to no regular screening failed to show any clinical benefit from regular screening (10). But the implication that screening was of no value is not valid. The reason is that the total follow up period was only 13 years, still a relatively short time interval for tiny tumors to grow enough to kill and we can assume that some of the men in the control group had PSA tests as part of routine care, decreasing the apparent effectiveness of screening in this study. So we cannot tell from it if screening was effective in saving lives.

Another very important fact about screening for any disease is that for any benefit to occur, there must be timely and proper follow up of a positive screening test. Screening for an early disease by itself does not affect the disease. For PSA screening, this requires prompt and proper evaluation of the person with the positive test and giving proper treatment if the evaluation shows that treatment is required. If this follow up is not available, then there is little if anything to be gained by having a PSA test.

Drawing useful conclusions about testing at this time is difficult. Here are some thoughts. We can assume that there are a few prostate cancers that are detectable by screening while they are so small that they can be removed before any spread, and if left alone, they would eventually spread and cause death. The statistics in the table above would suggest that in the low risk group, regular screening and treatment of prostate cancers would save 2 lives per 1,000 men and maybe more up to age 85 if regular screening started at age 50. For high risk men, the number would be 8 or more lives saved per 1,000 men under the same screening assumptions. How many more lives isn’t clear since U.S. government statistics show that the age-adjusted death rate for prostate cancer in the U.S. has decreased continually since 1992 with it now being 11% less than in 1992 (11). But around 600 of the 1,000 would have died of other causes, mainly cardiovascular diseases and cancer of other organs before they reached age 85. Cardiovascular disease is the big killer of men, not prostate cancer.

Some conclusions: When badly needed new research lets us know from tests which cancers will grow and spread and which will lie dormant for many years, then firmer recommendations about routine screening will be easier to make. For now, it makes sense to do PSA screening only when proper timely follow-up evaluations and treatments, when indicated, are available for men who have positive PSA tests. On a population basis it makes sense to screen high risk men at higher priority than low risk men. It seems that screening annually may be more frequent than necessary. It makes sense to give primary attention to screening for and treatment of cardiovascular risk factors since our present screening methods are more accurate at predicting trouble and our treatments are clearly more effective in preventing or delaying trouble from cardiovascular disease than preventing death from prostate cancer. A concern is that if we focus on and promote too many things that may be marginally beneficial, we can get distracted from doing enough of what is substantially beneficial.

References:

  1. Woolf SH, Krist A. Shared decision making for prostate cancer screening. Arch Int Med 2009; 169: 1557-9.
  2. 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.
  3. Wolf AMD, Wender RC, Etzioni RB, et al. American Cancer Society guideline for the early detection of prostate cancer. CA Cancer J Clin 2010; 60: 79-98.
  4. Hoffman RM, Couper MP, Zikmund-Fisher BJ, et al. Prostate cancer screening decisions. Arch Intern Med 2009; 169: 1611-8.
  5. Hoffman RM. Screening for prostate cancer. N Engl J Med 2011; 365: 2013-9.
  6. Surveillance Epidemiology and End Results (SEER) at http://seer.cancer.gov/statfacts/html/prost.html accessed Jan. 18, 2012.
  7. Howard K, Barratt A, Mann GJ, Patel MI. A model of prostate-specific antigen screening outcomes for low- to high-risk men. Arch Intern Med 2009; 169: 1603-10.
  8. Ben-Shlomo Y, Evans S, Ibraham F, et at. The risk of prostate cancer amongst black men in the United Kingdom: the PROCESS cohort study. Eur Urol 2008; 53: 99-105.
  9. Qaseem A, Alguire P, Dallas P, et al. Appropriate use of screening and diagnostic teats to foster high-value, cost-conscious care. Ann Intern Med 2012; 156: 147-9.
  10. Andriole G, Crawford ED, Grubb RL. Prostate cancer screening in the randomized prostate, lung, colorectal and ovarian cancer screening trial: mortality results after 13 years follow-up. J Natl Cancer Inst 2012; 104: 1-8
  11. http://seer.cancer.gov/faststats/selections.php?#Output


Posted 2/11/2012

The following update was posted 7/26/2012:

A randomized trial published July 19, 2012, compared 364 men with PSA-detected, early, localized prostate cancer who had prompt radical prostate surgery to 367 who had active surveillance, the term that more appropriately describes what has been called “watchful waiting.” The average follow up was 10 years. Forty-seven percent of the men operated on early died, nearly all from causes other than prostate cancer. Fifty percent of the surveillance group also died, similarly mostly from other causes. Twenty-five (6%) of the early operation group died of their prostate cancers as did 31 (8.4 %) of the surveillance group. Thus early surgery may lower prostate cancer mortality a bit compared to surveillance with surgery later when indicated by finding that the cancer is becoming more serious. But 287 men in the early surgery group had operations with their resultant adverse effects compared to only 37 in the surveillance group to save 6 more lives (31-25). More than anything else, this shows how much more we must learn to diagnose and distinguish harmful prostate cancers from harmless ones.

This new data supports all of the conclusions previously written.

Reference:

  • Wilt TJ, et al. Radical prostatectomy versus observation of localized prostate cancer. N Engl J Med 2012; 367: 201-13.

This note can be found online at http://www.weill.cornell.edu/cert/patients/prostate_cancer_screening.html

Health information for everyone from the Weill Cornell/HSS CERT http://www.weill.cornell.edu/cert/patients/

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