September is Prostate Cancer Awareness Month and it’s common to hear public service announcements reminding men to get a prostate-specific antigen (PSA) test. Afterall, prostate cancer is the second leading cause of cancer death among American men and early detection is the best prevention.
However, recommendations from the U.S. Preventive Services Task Force (USPSTF) cast doubt on whether the potential risks associated with PSA screening are worth the reward. Research suggests those risks may be exaggerated.
The long-term benefits of the PSA test for prostate cancer may outweigh any potential harm according to a paper published in the New England Journal of Medicine (NEJM). While current guidelines advise patients and physicians to determine the value of routine PSA screening on a case-by-case basis, researchers suggest that perceptions of PSA tests as ineffective are based on overstated harms and point to evidence showing that screenings can reduce death rates and prevent metastatic disease.
IMPACT OF PSA TEST FOR PROSTATE CANCER
PSA is a substance naturally produced by the prostate gland. A higher than normal PSA level can indicate various prostate-related issues, including infection, inflammation or cancer. By routinely measuring men’s PSA levels, physicians can watch for elevation over time to help determine whether further testing is needed.
In the early 1990s, the medical community began to see widespread adoption of the PSA test for prostate cancer. As a result, over the next three decades, the number of prostate cancer diagnoses rapidly increased, while the death rate saw a drastic decrease.1
However, from 2010-2020, PSA screening rates declined. This is most likely because data from two randomized trials suggested to some that the risks of screenings outweigh the benefits. Using the information from those trials, professional societies began to change their recommendations in the 2010s.2-4
The concerns of PSA screening include overdiagnosis and overtreatment. Overdiagnosis is the discovery of cancer that would not have been detected otherwise in a man’s remaining years. Overtreatment is the treatment of an overdiagnosed cancer and can cause unnecessary harmful side effects like urinary incontinence and erectile dysfunction.
“Currently much of the medical community considers PSA testing as an example of a screening tool that is ineffective largely based on short-term data from two trials,” said Dr. Yaw Nyame, co-lead author of the NEJM paper, written by researchers from the Seattle Cancer Care Alliance, University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, and Weill Cornell Medicine.
A PROBLEMATIC MISINTERPRETATION
The authors went on to say, “a prevailing opinion is that ‘two randomized trials of PSA screening showed equivocal or no benefit.’ This view is problematic.”
Critics of the two trials argue that they focused too heavily on survival statistics, failing to account for the quality-of-life-issues that come with advanced prostate cancer diagnoses, which can increase death rates from other comorbidities.
The perception of PSA screening as ineffective is rooted in short-term data from the two trials that suggests 1,000 screenings would detect 100 cancers, but only prevent one death. Those numbers have led the USPSTF and organizations including the American Academy of Family Physicians to shy away from recommending routine screening for men. Instead, they encourage “shared decision-making” between a patient and his physician on a case-by-case basis.
Newer research shows, however, that the decline in PSA screenings may have some unintended consequences, namely an increase in advanced prostate cancer diagnoses. A study published in the Journal of the National Cancer Institute reports an increase in regional-stage and distant-stage diagnoses (metastatic prostate cancer). This increase was accompanied by a decrease in local-stage disease, according to Dr. Ahmedin Jemal from the American Cancer Society, and colleagues.
RECONSIDERING THE TRADE-OFFS
Due to what Nyame and co-authors describe as a misinterpretation of the data and lack of attention to follow-up time, the researchers set out to reevaluate the long-term effects of the PSA test for prostate cancer using the most up-to-date data available.
“Using data from the more reliable of the two trials, and conservative assumptions, our team created a microsimulation model to extrapolate the mortality reduction due to screening from 16 years of follow-up and 25 years of follow-up,” noted Nyame. “Our results show that continued accrual of benefit over time creates a significantly more favorable picture of the value of screening.”
In contrast to the short-term ratio of 100 cancers preventing only one death, this new research looks longer-term, showing there would only need to be 11 extra prostate cancer diagnoses to prevent one death at 25-years of follow-up.
The authors also point out that the perceived harms of PSA screening do not take modern advances in medicine into account. This includes new technology that is improving detection of clinically significant prostate cancer, and an increase in the usage of low-risk cancer management methods like active surveillance.
“That is markedly reducing the harms of overtreatment,” said Nyame. “The time has come to rethink the use of PSA testing, particularly in high-risk populations, so that we do not miss the opportunity to improve our ability to diagnosis prostate cancer earlier, enhance our ability to treat it effectively, and save more men from serious illness and death.”
A FAVORABLE CONCLUSION FOR PSA TEST FOR PROSTATE CANCER
The study published in the NEJM offers evidence of how routine PSA testing can reduce death rates and prevent metastatic prostate cancer. The authors acknowledge that the balance between harm and benefit is still uncertain, but their findings lead them to believe the trade-off is favorable for PSA screening.
“As clinicians who screen, diagnose, and treat patients with prostate cancer and as statisticians who are devoted to understanding the effects of cancer screening,” the research team writes, “we suggest that the balance of benefits and harms of screening may be more favorable than is generally appreciated.”
Sources & Studies
- Analysis data. Surveillance, Epidemiology, and End Results Program, National Cancer Institute (https://seer.cancer.gov/seestat/analysis.html).
- US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;319:1901-13
- Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:120-34.
- Lee DJ, Mallin K, Graves AJ, et al. Recent changes in prostate cancer screening practices and epidemiology. J Urol 2017;198:1230-40.
- Shoag JE, Nyame YA, et al. Reconsidering the trade-offs of prostate cancer screening. N Engl J Med 2020;382:2465-2468.
- Jemal A, et al. Prostate cancer incidence 5 years after US Preventive Services Task Force recommendations against screening. J Natl Cancer Inst 2020; DOI:10.1093/jnci/djaa068.