<p><strong>When screening for prostate cancer, clinicians should use PSA as the first screening test. (<em>Strong Recommendation; Evidence Level: Grade A</em>) </strong></p>
Discussion
Discussion
<p>The PSA blood test remains the first-line screening test of choice based on randomized trials of PSA-based screening showing reductions in metastasis and prostate cancer death.<sup>21, 22</sup> At the time of this evidence review, very limited evidence has emerged regarding other candidates for first-line biomarkers or imaging.</p>
<p>Stockholm-3 (STHLM-3) has been evaluated as a first-line screening test for predicting the risk of GG2+ prostate cancers.</p>
<p>The STHLM-3 test is a multiplex test combining clinical variables (age, first-degree family history of prostate cancer, and previous biopsy), blood biomarkers (total PSA, free PSA, ratio of free to total PSA, human kallikrein 2 [hK2], macrophage inhibitory cytokine-1 [MIC-1], and microseminoprotein-beta [MSMB]), and a polygenic risk score (PRS). The STHLM-3 test has a higher predictive accuracy compared to PSA alone (area under the curve [AUC] 0.74 versus 0.56) and reduced unnecessary biopsies by 32%.<sup>23</sup> Using the STHLM-3 test and performing targeted plus systematic biopsies only in patients with MRI-suspicious lesions decreased overdetection and maintained the number of high-grade cancers found, as compared to systematic biopsy alone, in a screening-by-invitation trial.<sup>24, 25</sup> While this novel test appears promising, further validation in diverse populations to confirm these findings will be necessary to move forward into practice.</p>
<p>DRE should not be used as a first-line screening test prior to PSA, or a replacement for PSA in otherwise asymptomatic patients. In symptomatic patients, DRE can be considered as a diagnostic tool, rather than a screening test for cancer. It can be used as a complement to screening with PSA testing and is discussed in greater detail, including supportive references, under <strong>Statement 8</strong>.</p>