The United States Preventive Services Task Force (USPSTF) guidelines significantly altered the landscape of prostate cancer diagnosis and treatment. The last decade witnessed significant changes in prostate cancer epidemiology that evolved after the controversial grade D recommendation against PSA screening in 2012 (Fig. 1).¹ Within 2 years following its release, PSA screening in men aged 50 years or older significantly decreased by approximately 20%–39%, and the annual number of prostate biopsies decreased by 21% (Fig. 2).^2–4 As a result, the age-adjusted incidence of prostate cancer reached historical lows comparable to the pre-PSA era (Fig. 3)—100 cases per 100,000 men in 2014.

Figure 1. Watersheds in PSA screening in the United States during the last 2 decades.

Figure 2. PSA screening rates in the United States, 2005–2018. Source: Centers for Disease Control and Prevention, National Center for Health Statistics. National Health Interview Survey. Data age-adjusted to the 2000 U.S. population. https://progressreport.cancer.gov/detection/prostate_cancer.

Figure 3. Recent trends in age-adjusted incidence rates of prostate cancer, 2000–2019. Source: SEER Cancer Stat Facts: Prostate Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/prost.html. Data age-adjusted to the 2000 U.S. population.

Nonetheless, it is necessary to underline the context in which the Task Force issued this statement, as overdiagnosis of prostate cancer was rampant. First, PSA testing was associated with false-positive results (of up to 80% with a PSA cutoff of 4 ng/ml), negative psychological impact, biopsy-associated complications, and significant overtreatment.⁵ Moreover, the 2 large PSA screening randomized trials demonstrated overtreatment of 17%–50% of men diagnosed with prostate cancer.^6,7 According to recent estimates, the total number of men aged 50–84 overdiagnosed and overtreated for prostate cancer between 1986 and 2016 was up to 1.9 and 1.5 million, respectively.⁸

Using national representative outcomes from the SEER (Surveillance Epidemiology, and End Results) database, we discovered 2 important shifts in prostate cancer epidemiology attributable to changes in PSA screening.⁹ First, there was a significant decline in the incidence and treatment of Gleason Grade Group (GG)1 prostate cancer during the last decade. Between 2010 and 2018, the age-adjusted incidence rate of GG1 disease halved from 52 to 26 cases per 100,000 men, with the sharpest decline from 52 to 29 per 100,000 men occurring during 2010–2014. These changes occurred across all age groups but were more pronounced in men aged over 70 years with incidence rates declining from 189 to 98 cases per 100,000 men in 2014. After accounting for reporting delays to SEER registries, these trends coincided with the 2 USPSTF guidelines modifications in 2008 and 2012.^1,10 Notably, the fact that GG1 prostate cancer is no longer the most commonly diagnosed grade at biopsy reflects a significant epidemiological shift and suggests nationwide improvements in the proper stewardship of prostate cancer screening.

Nonetheless, considerable trade-offs accompanied these advancements as there was a significant increase in the incidence of high-grade and de novo metastatic prostate cancer in 2013, following the grade D USPSTF recommendation.^11,12 In 2017, we demonstrated that among men aged 75 years or older the incidence of metastasis at diagnosis increased following a nadir in 2011.¹¹ While multifactorial, these observations likely responded to the grade D recommendation issued in 2008 against prostate cancer screening in this age group.¹⁰ Separately, Jemal et al evaluated epidemiological trends by stage at diagnosis between 2005 and 2016 using the U.S. Cancer Statistics Public Use Research Database.¹³ The authors found a significant decline in the incidence of localized disease with a contrasting increased incidence in regional and metastatic prostate cancer at presentation. More recently, Desai et al demonstrated that rates of metastatic prostate cancer in men aged 45–74 years increased significantly from 12 to 17 per 100,000 men during 2010–2018 (annual percent change 5.3%).¹⁴ This contrasts with the stable incidence rate of de novo metastatic prostate cancer observed during 2004–2010 (Fig. 4). Undoubtedly, reduced screening led to some men missing a window of curability.

Figure 4. Recent trends in age-adjusted incidence rates of prostate cancer by ethnicity, 2000–2019. Brown indicates non-Hispanic Black, light blue indicates non-Hispanic White, navy blue indicates Hispanic, and pink indicates non-Hispanic Asian/Pacific Islander males. Source: SEER Cancer Stat Facts: Prostate Cancer. National Cancer Institute. https://seer.cancer.gov/statfacts/html/prost.html. Data age-adjusted to the 2000 U.S. population.

Beyond the impact of screening practice changes, we explored other factors that may concurrently affect prostate cancer epidemiology. These include an increase in the prevalence of obesity, which is associated with a lower likelihood of low-grade and increased high-grade prostate cancer, and the utilization of tests in the pre-biopsy setting, such as biomarkers and prostate MRI. Nonetheless, the prevalence of obesity among men in the United States increased at a steady pace and over an extended period (approximately 20% increase during the last 2 decades), and the adoption of pre-biopsy MRI and biomarkers in the United States remains relatively low, with the highest utilization rate of 19% and 13% in 2019, respectively.^15,16 These changes contrast with the rather steep decline in low-grade prostate cancer observed during the early 2010s. Similarly, PET (positron emission tomography)-CT may contribute to more detection of metastases at diagnosis because of its higher sensitivity compared to bone and CT scans. However, PET-CT scans were sparingly used during the last decade and received U.S. Food and Drug Administration approval for staging in 2020.^17,18

The demonstration of significant contamination in the control arm of the PLCO (Prostate, Colorectal, Lung, and Ovarian Cancer Screening) trial, which had shown no benefit of PSA screening, as well as the increasing rates of metastatic disease and significant declines in overtreatment,^19,20 made the USPSTF issue a grade C recommendation in 2018, advocating for shared decision making for screening men aged 55–69 years.²¹ While this statement is more in consonance with the current evidence and other professional cancer societies, it is necessary to avoid a swing back to indiscriminate testing. Leapman et al recently demonstrated a reversal in the decline of PSA screening rates after the grade C recommendation, as evidenced by a 13% relative increase (95% CI, 1.1%–24%) among insured men during 2016–2019.²² However, these increasing trends were also seen among men aged 40–54 years and 70–89 years, who may be less likely to benefit from PSA screening. Certainly, the downstream consequences of this reversal in PSA screening rates will take many years to manifest.

Reconciling population and individual perspectives on PSA screening remains a considerable challenge as there is a delicate balance between early detection of lethal prostate cancer and prevention of overdiagnosis and overtreatment. This is illustrated by the increase in higher grade, metastatic disease at diagnosis vs a decrease in the incidence of GG1 prostate cancer. Moving forward, implementation of PSA screening tailored to individualized patients’ risk and limited to men who would benefit, paired with a restrictive approach to biopsy and treatment, may be the key to resolving the PSA screening controversy.