Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer death in men worldwide.1 An estimated 174,650 new cases are diagnosed each year in the United States; 31,620 American men die annually from the disease.2 Although prostate cancer can be a serious disease, many men do not die from it. In fact, 2.9 million men who were diagnosed with prostate cancer at some point are alive today.3
Risk factors. Prostate cancer develops mainly in men ages ≥ 65 years and rarely occurs before age 40. In addition to age, family history and African American ethnicity are the major nonmodifiable risk factors for prostate cancer.4 From the 1970s to the most recent statistical analysis of the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, African American men have continued to have significantly higher incidence of, and mortality rates from, prostate cancer than their European American counterparts. African American men are also more likely than men of European ancestry to have aggressive prostate cancers.5 Other risk factors include geographic location (higher risk in Northern Europe, North America, and Australia; lower risk in Asia, Africa, and South and Central America), mutations in the BRCA2 gene, and hereditary non-polyposis colon cancer syndrome.4
Prostate-specific antigen (PSA) was first used as a screening tool for prostate cancer in 1991.6 Prostate cancer incidence, especially organ-confined disease, has dramatically increased since then.7 PSA testing has a low sensitivity and specificity for the detection of prostate cancer, and there is no clear threshold at which biopsy can or should be offered. The most commonly used cutoff value of 4 ng/mL has a false-positive rate of about 70%.8
Benign prostatic conditions such as hypertrophy and infection can elevate PSA levels. In addition, the PSA test does not distinguish between aggressive and slow-growing cancers, and about 15% of patients with prostate cancer have a normal PSA level.9
A word about the digital rectal exam. While PSA testing has been the mainstay of prostate cancer screening, a few studies have included digital rectal exam (DRE) in their protocols. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed that DRE captured an additional 2% of men with prostate cancer in the setting of a normal PSA test result.10 In the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, the overall detection rate for prostate cancer was found to be better when DRE was combined with PSA and prostate biopsy than when DRE was used alone (4.5% vs 2.5%).11 Nevertheless, generally speaking, DRE can be omitted in the era of PSA screening.
Screening guidelines vary
Recommendations for prostate cancer screening vary by organization and are summarized in TABLE 1.9,12-14 In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer (Category D).15 In 2018, USPSTF provided an update with a new recommendation that clinicians inform men ages 55 to 69 years about the potential benefits and harms of PSA-based screening (Category C).14 The USPSTF continues to recommend against PSA-based screening for men ages ≥ 70 years (Category D).14
Does PSA-based screening improve patient-centered outcomes?
Several randomized controlled trials (RCTs) such as the Quebec Prospective Randomized Controlled Trial,16 the Norrköping Sweden Study,17 ERSPC,11 and PLCO10 have been conducted to assess the benefits of PSA testing. PLCO and ERSPC have contributed significantly to our understanding of prostate cancer screening even though their 13-year follow-up results are conflicting (TABLE 2).10,11,18
Continue to: In the ERSPC 13-year follow-up publication...