A Pragmatic Approach to Prostate Cancer Screening

Abstract

The introduction of prostate-specific antigen (PSA)-based screening for prostate cancer in the early 1990s was followed by a nearly 2-decade long decline in prostate cancer metastasis and mortality. 1 However, clinical trial data revealed that screening was associated with substantial harms. 2 Under the traditional clinical approach in which elevated serum PSA triggered prostate biopsy, roughly 1 in 5 screened men underwent biopsies, with more than 75% found to be negative and a majority of positive biopsies harboring low-grade, clinically insignificant cancers. 3 Prostate biopsies are uncomfortable for patients and carry a risk of bleeding and infection requiring hospitalization. 4 Moreover, during a previous era in which a cancer diagnosis was inexorably linked to treatment, overdiagnosis (ie, detection of indolent cancers that would not have been detected during life in the absence of screening) and overtreatment resulted in significantly reduced quality of life. 5 In 2012, the US Preventive Services Task Force (USPSTF) provided a grade D recommendation against the use of PSA screening, concluding that the benefits of PSA-based screening for prostate cancer do not outweigh the harms. 6 In the time since, longer-term outcomes from highquality studies have better informed the benefits of screening. After 22 years of follow-up in the Gotebörg screening trial, 7 the rate ratio for prostate cancer death in screening participants was 0.59 (95% CI, 0.43-0.80), with a number needed to invite to screening of 221 and number needed to treat of 9 to prevent 1 death from prostate cancer-figures that compare favorably with other common cancers. 8,9 At the same time, a growing understanding of prostate cancer has led to advances to reduce the harms previously associated with screening. For men with favorable-risk cancers, adoption of active surveillance-a management strategy centered on monitoring rather than immediate treatment-has reduced overtreatment and its associated adverse effects. 10 In large part due to these studies quantifying benefit and development of approaches to minimize harms, in 2018 the USPSTF offered an updated grade C recommendation for PSA screening, recommending individualized decision-making in men aged 55-69 years. 11 Current clinical guidelines emphasize a narrowed diagnostic focus on identifying higher-grade cancers, recommending that patients with an elevated PSA level undergo magnetic resonance imaging (MRI), if available, or biomarker testing to better define the risk of high-grade (grade group [GG] ≥2) disease prior to biopsy. 12-14 Indeed, MRI with targeted biopsy improves detection of high-grade cancers relative to stan-Multimedia