Study Links Decline in PSA Screening to Increased Incidence of Advanced Prostate Cancer

Decreases in local-stage and increases in distant- and regional-stage prostate cancer incidence could be the result of a recommendation issued by the US Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA)—based screenings, according to findings from a study published in the Journal of the National Cancer Institute. ¹

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnosis (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,” Ahmedin Jemal, DVM, PhD, and colleagues, wrote in the paper.

In the study, investigators examined patterns in invasive prostate cancer incidence from 2005 to 2016 by utilizing data from the US Cancer Statistics Public Use Research Database. The study investigated over 2 million prostate cancer cases, taking age group, ethnicity, and disease stage into consideration.

Results showed a yearly 6.4% decrease (95% CI, 4.9%-7.9%) in local-stage disease incidence in men aged 50 to 74 years from 2007 to 2016. Likewise, patients aged ≥75 years saw yearly decreases in local-stage prostate cancer of 10.7% (95% CI, 6.2%-15.0%) over the course of 6 years (2007-2013). While both age groups saw lower incidence of local-stage disease, regional- and distant-stage prostate cancer incidence increased yearly in both age groups. For example, distant-stage incidence increased by 5.2% (95% CI, 4.2%-6.1%) annually in men aged ≥75 years from 2010 to 2016.

The findings indicate that the rise in advanced cases could be linked with a 2008 USPSTF recommendation against PSA screening for men over the age of 75, which was eventually expanded in 2012 to include men of all ages.

The organization reasoned that the harm caused by numerous false positives and potential psychological distress could outweigh the benefits of this once standard testing procedure.² The statement expresses concern that too many early prostate cancer diagnoses can lead to unneeded testing, such as biopsies, and treatment, which can result in numerous chronic issues, such as incontinence, erectile dysfunction, and bowel problems.

The task force later revised its recommendation in 2018, acknowledging the small mortality benefit PSA testing may provide men with prostate cancer within the 55-69 age group.³ This decision was made after the USPSTF analyzed data from randomized clinical trials that indicated PSA testing could prevent as many as 1.3 prostate cancer—related deaths per 1,000 men tested over the course of 13 years in patients between the ages of 55 and 69 years.

“For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician,” the task force stated. They still remained steadfast, however, that men over the age of 70 should abstain from testing.

While the USPSTF eventually revised its statement, this shifting opinion could indicate a lack of data backing the recommendation. This point was raised by William K. Kelly, DO, in an interview with OncLive in March 2018. “When you see a task force go back and forth, that means there are limited data to guide them; there are not black-and-white data, it’s really gray,” said Kelly. “Many things go into a decision about active surveillance—not only about the tumor type, but it is based on anywhere from the pathology to the genomics to other characteristics. We have to also include the patient preferences because they actually drive [the decision]. We need to understand patient preferences and their comorbidities.”

Further results from the study showed that for local-stage disease, incidence rates per 100,000 men aged ≥50 increased from 456.4 (95% CI, 454.2-458.6) in 2005 to 506.1 (95% CI, 503.9-508.3) in 2007; incidence decreased in subsequent years to 279.2 (95% CI, 277.7-280.6) in 2016. With regard to regional-stage disease, a general increase in incidence was observed throughout the study period, going from 5.7 (95% CI, 5.4-5.9) in 2005 to 9.0 (95% CI, 8.8-9.3) in 2016. For those with distant-stage disease, incidence rates were found to slightly decrease, going from 23.1 (95% CI, 22.6-23.6) in 2005, to 22.4 (95% CI, 21.9-22.9) in 2008, but then continued to increase to 29.7 (95% CI, 29.2-30.2) in 2016.

For all race/ethnicities combined, investigators reported that the incidence patterns for those between the ages of 50 and 74 and those ≥75 years were similar to those aged ≥50 years. Incidence rates after the late 2000s were found to decline for local-stage disease but increase for regional- and distant-stage diseases, although local-stage disease appeared to stabilize from 2013 to 2016 in those aged ≥75 years. Additionally, similar age- and stage-specific incidence patterns were observed in non-Hispanic white men and non-Hispanic black men. However, the incidence in the latter who were aged ≥75 years during the most recent period continued to decrease for local-stage disease and stabilized for distant-stage disease.

Although the data indicate a significant decline in the racial disparity in the incidence of distant-stage disease, which was confined to men between the ages of 50 and 74 years and coincided with a steeper increase in distant-stage prostate cancer incidence in non-Hispanic white men. Despite this, distant-stage incidence rates in non-Hispanic black men continues to be 2, or even 3, times as high as what is seen in non-Hispanic white men in ages 20 to 74 years, and 65% higher in those aged ≥75 years. The reasons for this disparity are still not understood, according to the investigators.

“Reasons for the continued increase in regional- and distant-stage incidence rates are unknown. Family history, an established risk factor for prostate cancer, is unlikely to change during the study period,” the investigators write. “Cigarette smoking, which increases the risk of fatal prostate cancer, is also unlikely to account for observed trends because of the long-term declines in smoking and in tobacco-related cancers.” The investigators added that although excess body weight is another risk factor associated with fatal prostate cancer, the extent of its contribution to the rising rates of distant-stage incidence remains still unknown.

Although the decrease in early stage prostate cancer incidence may seem promising, this could be because less patients are undergoing regular screenings that would otherwise reveal the early stages of illness, and instead are being tested only when symptoms are presenting in later stages. Based on this assessment, Jemal believes that the USPSTF’s recommendation against PSA testing could be a potential explanation for the rise in more advanced cases over the years.

Although the evidence points to the USPSTF’s statement as a strong reason for the increase in regional- and distant-stage prostate cancer cases, the investigators conclude that further research is needed to further narrow down and refine the reasons for the spike in cases.

“The persistently increasing regional- and distant-stage prostate cancer incidence during the past 5 years has public health implications given the substantial morbidity and premature mortality associated with it and the recent stabilization of prostate cancer death rates after a steady decline since the early 1990s,” the investigators conclude. “Future studies are needed to elucidate reasons for the rising incidence trends for regional- and distant-stage diseases and for the disproportionately high burden of the disease in black men.”

References

1. Jemal A, Culp MBB, Ma J, PhD, et al. Prostate cancer incidence 5 years after US Preventive Services Task Force Recommendations against screening [published online May 20, 2020]. J Natl Cancer I. doi:10.1093/jnci/djaa068
2. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(3):185-191. doi:10.7326/003-4819-149-3-200808050-00008
3. Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(18):1901‐1913. doi:10.1001/jama.2018.3710