Background Lowering the prostate-specific antigen (PSA) cut-off from 3.0 to 1.8 ng/ml in prostate cancer (PCa) screening would improve diagnostic yield but substantially increase the number of men undergoing diagnostic work-up. Objective To evaluate 4Kscore as a reflex test for pre-magnetic resonance imaging (MRI) risk stratification among men with PSA 1.80–2.99 ng/ml. Design, setting, and participants This diagnostic biomarker study was nested within the population-based Göteborg-2 PCa screening trial and included men with PSA ≥1.80 ng/ml who were referred for MRI and provided blood for biomarker research, followed by targeted biopsy if MRI-positive (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The analysis included 555 men (median age 59 yr) with PSA 1.80–2.99 ng/ml, pre-MRI 4Kscore, and assessable MRI. Outcome measurements and statistical analysis The primary outcome was International Society of Urological Pathology (ISUP) grade ≥2. Diagnostic performance of 4Kscore as a pre-MRI reflex test was assessed using sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUC), with 95% confidence intervals (CI). Results and limitations MRI was positive in 116/555 men (21%). Overall, PCa was detected in 52/555 men (9.3%), including 27/555 men (4.9%) with ISUP grade ≥2. A 4Kscore ≥7.5% would detect 56% of the ISUP grade ≥2 cancers and reduce detection of ISUP grade 1 by 64%. This approach would reduce MRI referrals by 71% and referrals to biopsy by 67% compared with performing MRI in all men with PSA ≥1.80 ng/ml and performing biopsies in all men with suspected lesions. With a 4Kscore cut-off of 7.5%, sensitivity and specificity for detecting ISUP grade ≥2 were 56% (95% CI = 35–74) and 72% (95% CI = 68–76), respectively. The AUC was 0.69 (95% CI = 0.58–0.79). The limited number of clinically significant PCa cases restricts generalizability. Conclusions Using a 4Kscore 7.5% cut-off as a reflex test before MRI in men with PSA 1.80–2.99 ng/ml could substantially reduce referrals to MRI and biopsy, reduce ISUP grade 1 cancer detection, and enable earlier detection of about half of ISUP grade ≥2 cancers. Many men with ISUP grade ≥2 cancers had 4Kscores <7.5%, and most men selected for MRI had PI-RADS <3. Evaluation of lower 4Kscore cut-offs, longer follow-up, and larger prospective studies is required before clinical implementation.
Background and objective This study evaluated the added value of systematic biopsies (SBx) in addition to targeted biopsies (TBx) for detecting upgrading during repeat biopsies on active surveillance (AS) using data from the Prostate Cancer Research International Active Surveillance study. Methods We analyzed repeat biopsies of men who underwent magnetic resonance imaging (MRI) and SBx at diagnosis, with or without TBx depending on the presence of an MRI lesion, had at least one positive (Prostate Imaging Reporting and Data System 3–5) follow-up MRI, and received both SBx + TBx at subsequent repeat biopsy. Upgrading compared with diagnostic biopsy was assessed for TBx only, SBx only, and both, using three definitions: any upgrading, upgrading to grade group (GG) ≥2 with cribriform growth or intraductal carcinoma (≥GG2+), and upgrading to ≥GG3. Cumulative incidences were calculated using each detection method as competing events. For upgrading ≥GG2+ detected by SBx only, the laterality relative to the MRI lesion was determined. Key findings and limitations We analyzed 650 repeat biopsies in 568 patients with a median follow-up of 3.0 yr (interquartile range = 1.8–4.3) for men still on AS. During available follow-up, any upgrading occurred in 238 biopsies (37%), of which 47 (7.2%) were detected by SBx only. Upgrading to ≥GG2+ and ≥GG3 was observed in 100 biopsies (16%) and 78 biopsies (12%), respectively, with SBx alone identifying 19 (3.0%) and 15 (2.3%) of these patients. At 6 yr, the cumulative incidence of ≥GG2+ upgrading was 27% (95% confidence interval [CI] = 21–32%), with 5.4% (95% CI = 2.9–9.1%) for upgrading detected exclusively by SBx. Three of the 19 cases with upgrading to ≥GG2+ detected by SBx only were located contralateral to the MRI lesion (0.5% of all biopsies). Limitations include the retrospective design, which may introduce selection and registration biases. Conclusions and clinical implications In men on AS who underwent diagnostic MRI with SBx (with or without TBx) and a positive follow-up MRI, SBx has limited added value during repeat biopsies, particularly for contralateral sampling, supporting a targeted and perilesional biopsy approach.
