Nearly five years later, it appears that the decision of US Preventive Services Task Force (USPSTF) to reverse its recommendations that discouraged prostate cancer screening has resulted in a significant rebound in specific antigen (PSA) screening rates. According to a new study published in the Nov. 11 issue of JAMA Oncology, PSA testing rates for men ages 40 to 89 from 2016 to 2019 grew at a 12.5 percent clip.
Problems with PSA Screening
Current PSA tests can detect high levels of the prostate-specific antigen protein in the blood. The problem is in interpreting the results. Stated simply, PSA is not a reliable biomarker. High levels of PSA is a potential sign of prostate cancer; but it could also be a sign of infection, inflammation or other less nefarious disease. In some cases, high PSA is caused not by disease but just the common age-related condition of an enlarged prostate gland. But given the risks involved, when screening tests show high PSA levels, biopsies are ordered to rule out cancer. Not surprisingly, a large percentage of these biopsies prove unnecessary.
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Another problem with PSA testing is that it over detects for low-grade cancers that do not pose a threat to the patient. This can result in treatment that leads to erectile dysfunction, urinary incontinence and other side effects that do more harm than the actual cancer.
The USPSTF Guidelines
In 2012, the influential USPSTF published guidelines assigning PSA testing a grade of D and advising against PSA-based prostate cancer screening in all men. Based on moderate to high certainty, the 2012 guidance concluded that the harms of PSA screening outweighed its benefits. After the 2012 guidance was incorporated into clinical practice, PSA testing and diagnostic biopsy rates in the US decreased measurably, as did the number of prostate cancers identified. These reductions might be associated with the increase in actual incidence of prostate cancers diagnosed at an advanced or metastatic stage during this period, according to the study authors.
In April 2017, the USPSTF published a draft guideline reversing its 2012 guidance. The 2017 revised guidelines, which were finalized in May 2018, endorsed individual decision-making on PSA testing for men ages 55 to 69, boosting it from grade D to grade C.
The JAMA Oncology Study
To evaluate the association between the USPSTF upgrade and PSA testing rates, researchers from Yale University and the University of California, San Francisco, performed a retrospective cohort study of over 8 million men with private insurance. “We sought to identify patterns of testing in the age group specified in the guideline—55 to 69 years—as well as among those for whom screening remains without recommendation—40 to 54 years—or discouraged—70 years or older—by the USPSTF guideline,” wrote lead author, Dr. Michael Leapman of Yale School of Medicine.
Using de-identified claims data from Blue Cross Blue Shield beneficiaries ages 40 to 89 from January 2013 through December 2019, the team calculated age-adjusted PSA testing rates in bimonthly periods. They then compared PSA testing rates for the calendar year before (January 1 to December 31, 2016), and calendar year after (Jan. 1 to De. 31, 2019) the change in USPSTF guidelines took place.
The authors used statistical analyses to compare the April 2017 draft and May 2018 published USPSTF guideline with actual rates of PSA testing. Changes in PSA testing rates were also evaluated among beneficiaries within the ages reflected in the guideline: i.e., those between 40 to 54 years, 55 to 69 years, and 70 to 89 years.
Findings of the Study
The overall mean rate of PSA testing increased 12.5 percent, from 32.5 to 36.5 tests per 100 person-years between 2016 and 2019, the researchers found. Mean rates of PSA during the same period increased:
- From 20.6 to 22.7 tests per 100 person years among men ages 40 to 54, a relative increase of 10.1 percent;
- From 49.8 to 55.8 tests per 100 person years among men ages 55 to 69, a 12.1 percent relative increase; and
- From 38 to 44.2 tests per 100 person years among men ages 70 to 89, a relative increase of 16.2 percent.
PSA testing for all beneficiaries increased significantly after the April 2017 revised USPSTF draft guidance date. In addition to the draft, the researchers theorized that increased PSA screening rates might have also been the result of continued encouragement of screening by advocacy groups, politicians, celebrities and others in the years preceding the 2017 draft guidance. among all beneficiaries.
The Downside of Encouraging PSA Screening
PSA screening remains problematic and the decision of whether to recommend it is far from easy. Thus, the November 11 JAMA Oncology edition carrying the Yale, UCSF study is accompanied by a related opinion from Dr. Freddie Hamdy of the University of Oxford addressing the challenges to recommending PSA testing as a public health screening policy for prostate cancer, including:
- Avoiding overdetection of disease that would not otherwise manifest itself as clinically important;
- Inevitable overtreatment with potential adverse effects on quality of life; and
- The inability to determine accurately the lethal potential of prostate cancer at diagnosis, resulting in under-treatment.
“It has been clearly demonstrated that screening by PSA testing saves lives, but at the unacceptable cost of overdetection and overtreatment,” notes Hamdy, cautioning against inappropriate PSA testing outside evidence-based recommendations.
| Other Promising Potential Biomarkers for Prostate Cancer |
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While PSA screening remains the primary method of detecting prostate cancer, its low rate of specificity (20 to 45 percent), results in a high number of unnecessary prostate biopsies. The utility of PSA screening in diagnosing cancer, as opposed to infections and other non-cancerous conditions that can elevate PSA levels, is also impaired by its inability to identify whether the detected cancer requires active intervention or simple surveillance. As a result, laboratory scientists have been working to develop minimally invasive prostate cancer biomarkers to accurately distinguish low-risk from aggressive disease. Promising candidates include:
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| Source: This content draws from an article entitled “Urine Biomarkers Show Promise for Prostate Cancer,” by Oreoluwa Ogunyemi, MD, that was originally published in Clinical Lab Manager on July 6, 2021. It is reprinted here with permission. |