As we continue our series on prostate cancer, we must address the subject that is most controversial about prostate cancer, i.e., the utility of screening. In the past, the use of serum prostate-specific antigen (PSA) testing in conjunction with digital rectal exams was the candidate tool for screening. However, it has become recognized that most clinicians, aside from well-trained urologists, do not do adequate digital prostate examinations and thus current questions regarding the utility of screening revolve around the blood test alone.
Both laymen and clinicians may have difficulty in appreciating that the goal of screening is not to diagnose or find more cancer. As we have discussed in prior articles, the prevalence of indolent undiagnosed prostate cancer is widespread in men of middle and older ages so any concerted efforts to biopsy the prostate after PSA screening will inevitably diagnose many prostate cancer cases. The real goal of screening, however, is to reduce cancer-associated mortality in a reasonably cost-effective manner and with a reasonable level of adverse effects. Simply diagnosing more cancers does not automatically mean we affect its mortality outcomes.
I always rely on the U.S. Preventive Services Task Force, which provides recommendations for cancer screening—its approach to evaluation is widely respected and generally unbiased. Until its 2012 review, the USPSTF did not recommend prostate cancer screening at all because there were no studies that clearly demonstrated a reduction in prostate cancer-related mortality as a result of screening. In 2018, it changed its recommendation to include shared decision-making for average-risk men 55-69 years of age; specifically, these men should discuss the small potential benefits along with the potential adverse effects of screening with their healthcare providers before initiating screening. The USPSTF continues to advise against screening for those over age 70.
The introduction of widespread PSA screening in the 1980s led to almost triple the diagnoses of prostate cancer in the U.S., but there was no concomitant reduction in mortality—because of the high prevalence of indolent undiagnosed prostate cancer, PSA is very good at finding prostate cancer. The question remained as to whether it can reduce mortality in an efficient way. For this question, randomized trials were necessary. The 2018 recommendations reflected the maturing of data from three randomized trials that addressed this issue.
Two of the studies found no difference between the screened and the control groups. The PLCO Screening Trial (Prostate, Lung, Colorectal, Ovarian) randomized 76,683 men to PSA screening or not and, after 15 years of follow-up, found a prostate cancer death rate of 4.8/1000 person-years for the screening group and 4.6/1,000 person-years for the control group, but the study had many flaws, with contamination in the control group (many had PSA screening inadvertently), and more screening of men in the intervention group prior to the trial.
The CAP trial (Cancer of the Prostate) was conducted in the U.K. It was a randomized trial among 415,357 men, where the randomized men received a single invitation for a PSA screening test; only 34% of those invited showed up for a PSA test. After a 10-year follow-up, the prostate cancer mortality rate was equal between the screened and control groups (0.30/1,000 person-years versus 0.31/1,000 person-years). Since the analysis was by intent to treat and only 34% received screening, it is difficult to assess the import of these results.
The third randomized trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), did find a small mortality benefit for screening. They randomized 181,999 men aged 50-74 years in 7 countries. The screening interval and the PSA threshold for biopsy varied by country. After a median follow-up of 13 years, the prostate cancer mortality was 4.3/10,000 person-years in the screening group versus 5.4/10,000 person-years in the control group, a risk reduction of 1.1 deaths per 10,000 person-years or 1.3 fewer prostate cancer deaths per 1000 men. The number needed to invite screening to prevent one prostate cancer death was 781 and the number of prostate cancers diagnosed in order to prevent that prostate cancer death was 27.
In summary, based on the ERSPC trial, if you screen 1,000 men ages 55-69 for 13 years, you will diagnose 27 prostate cancers in that group over the 13 years and ultimately prevent 1.3 prostate cancer deaths. There was no demonstrable benefit for men over age 70.
In terms of harms of screening, there is the cost and effort of screening 1,000 men every one to two years for 10 years. This results in frequent false-positives—over 10 years of screening, more than 15% of the men (150 men) experienced at least one false-positive result necessitating a biopsy (it is worth pondering that for a moment—it is an extraordinary figure). Estimates suggest that 20%-50% of the prostate cancers diagnosed through screening are over-diagnosed (would never become clinically symptomatic or meaningful). When men are treated for those 27 cancers that are diagnosed, those who undergo radical prostatectomy have a 20% rate of long-term urinary incontinence requiring the use of pads and two-thirds develop long-term erectile dysfunction; somewhat lower rates of these adverse effects result from radiotherapy.
I would just make two other points. The data and recommendations above are for average risk men; other considerations may apply for those with elevated risk—those of African descent, family history, BRCA mutations, etc. Most clinicians initiate these discussions at about 50 years of age.
As a final comment on how prostate cancer screening is actually practiced in the U.S., data from the CDC indicates that in 2005 (when the USPSTF did not recommend screening), approximately 46% of men ages 55-69 years old had a PSA screening test in the prior year, while 53% of those over age 70 did. The introduction of shared decision-making led to a decrease in screening, so that in 2021, 37% of men 55-69 years old had a PSA screening test while 47% of those over 70 years did.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
