Patient characteristics and relevant imaging and biopsy data are described in Table 1.

Of the 918 included patients, cs-PCa (GG ≥ 2) was detected in 386 (42.0%) of patients by systematic biopsy alone, 315 (34.3%) patients by MRI -targeted biopsy alone, 382 (41.6%) by either MRI-targeted or US-targeted biopsy (i.e., either targeted biopsy), and 484 (52.7%) by combined targeted and systematic biopsy (Fig. 1). Systematic biopsy alone detected more cs-PCa than MRI-targeted biopsy alone (p < 0.001). There was no difference between systematic biopsy and the combination of MRI-targeted and US-targeted biopsy in the rate of cs-PCa detection. Low-grade prostate cancer (GG 1) was detected in 371 (40.4%) patients by systematic biopsy alone, 235 (25.6%) patients by MRI-targeted biopsy alone, 238 (25.9%) patients by targeted biopsy, and 306 (33.3%) patients by targeted and systematic combined biopsy. Systematic biopsy alone detected more low-grade PCa than MRI and US-targeted biopsy (p < 0.001) or MRI-targeted biopsy alone (p < 0.001).

Rates of cs-PCa detection (ISUP Grade Group [GG] of 2 or greater) by systematic biopsy, MRI target biopsy, MRI and US target biopsy, and combined biopsy (systematic biopsy, MRI target biopsy, and US target biopsy; n = 918)

A total of 484 patients were diagnosed with cs-PCa by both systematic biopsy and MRI as well as US-targeted biopsy. MRI and US-targeted biopsy detected cs-PCa in 382 (79.0%) of those 484 patients, while systematic biopsy detected cs-PCa in 386 patients (79.8%, Table 2). Of the 918 patients included patients, systematic biopsy made clinically significant upgrades with GG ≥ 2 in 132 (14.4%) patients, with GG ≥ 3 in 55 patients (6.0%), and with GG ≥ 4 in 17 patients (1.8%, Table 2) compared to targeted biopsy. Conversely, targeted biopsy made clinically significant upgrades with GG ≥ 2 in 130 patients (14.2%), with GG ≥ 3 in 50 patients (5.4%), and with GG ≥ 4 in 19 patients (2.1%, Table 2) compared to systematic biopsy.

PSA density ≥ 0.15 ng/ml2 was associated with the detection of clinically significant prostate cancer by systematic biopsy (OR 2.66, 95% CI 2.03–3.49, p < 0.001).

Upgrade by systematic biopsy occurred in 18.4% (60/326) of patients without US lesions and in 12.7% (75/592) of patients with US lesions. The presence of a visible US target was associated with a lower odds of upgrade by systematic biopsy [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.44–0.93, p = 0.02, Table 3]. This association persisted in a model that included age and PSA density as predictors (OR 0.62, 95% CI 0.43–0.90, p = 0.01, Table 3). The presence of prior PCa, presence of concordant US/MRI lesions, maximum PIRADS score, PSA density, and age were not associated with clinically significant upgrade by systematic biopsy (Table 3).

The 918 included patients comprised 5508 prostate gland sextants. Of these sextants, 3534 (64.2%) had no lesions visible on MRI or US, 1228 (22.3%) had lesions visible on MRI but not US, 242 (4.4%) had lesions visible on US but not MRI, and 504 (9.2%) had lesions visible on both MRI and US (Fig. 2). Cs-PCa was detected less often by systematic biopsy in sextants without MRI or US lesions [7.5% (266/3534)], and more often in sextants with lesions visible on MRI only [19.0% (233/1288)], US only [18.2% (44/242)], or both MRI and US [37.1% (187/504)] (Fig. 2). Furthermore, cs-PCa was detected least often [3.9% (59/1527)] in sextants without ipsilateral US or MRI lesion. Cs-PCa was significantly more likely to be detected on systematic biopsy in sextants with an MRI lesion (OR 4.15, 95% CI 3.37–5.10, p < 0.001), with an US lesion (OR 4.66, 95% CI 3.62–5.99, p < 0.001), and with an ipsilateral target (OR 9.03, 95% CI 6.41–12.72, p < 0.001).

Sextant-level detection of cs-PCa by systematic biopsy in 5508 sextants based on the presence or absences of lesions visible on MRI and US

Of the 5508 sextants from the 918 patients in our cohort sampled by systematic biopsy, 191 (3.5%) led to clinically significant upgrade by systematic biopsy that were not detected by MRI or US-targeted biopsy. The odds of an upgrade with systematic biopsy were significantly higher for sextants with an MRI target (OR 2.58, 95% CI 1.87–3.63, p < 0.001, Table 4). The presence of an MRI target was associated with upgrade in sextants without US lesions (OR 2.87, 95% CI 1.94–4.25, p < 0.001), but not in sextants with US lesions (OR 1.01, 95% CI 0.39–2.61, p = 0.98, Table 4). The odds of an upgrade with systematic biopsy were significantly higher for sextants with an US lesion (OR 1.83, 95% CI 1.14–2.93, p = 0.01. Table 4). The presence of an US target was associated with upgrade in sextants without MRI lesions (OR 2.45, 95% CI 1.08–5.58, p = 0.03), but not in sextants with MRI lesions (OR 0.86, 95% CI 0.46–1.62, p = 0.65, Table 4). Clinically significant upgrades were also statistically more likely to be made in sextants with ipsilateral lesions compared to those without (OR 3.89, 95% CI 2.36–6.42, p < 0.001, Table 4). The association of MRI lesions, US lesions, and ipsilateral lesions did not differ by PSA density.