Incorporating Magnetic Resonance Imaging and Biomarkers in Active Surveillance Protocols - Results From the Prospective Stockholm3 Active Surveillance Trial (STHLM3AS)

Abstract

Background: Active surveillance (AS) for men with low-risk prostate cancer (PC) can lead to patient morbidity and healthcare overutilization. The aim of this study was to evaluate an AS protocol using the Stockholm3 test and magnetic resonance imaging (MRI) to reduce biopsy intensity.

Methods: We conducted a prospective multicenter study of 280 invited men from a contemporary screening study (STHLM3), with Gleason Score (GS) 3 + 3 PC on a current AS protocol. Patients underwent prostate-MRI and blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic variants, and clinical variables to predict risk of GS ≥3 + 4 PC followed by systematic biopsies and targeted biopsies (for Prostate Imaging Reporting and Data System version 2 ≥3 lesions) in all men. Primary outcomes were reclassification to GS ≥3 + 4 PC and clinically significant PC (csPCa), including unfavorable intermediate risk PC or higher based on National Comprehensive Cancer Network guidelines.

Results: Adding MRI-targeted biopsies to systematic biopsies increased sensitivity of GS ≥3 + 4 PC compared with systematic biopsies alone (relative sensitivity [RS] = 1.52, 95% confidence interval [CI] = 1.28 to 1.85). Performing biopsies in only MRI positive increased sensitivity of GS ≥3 + 4 PC (RS = 1.30, 95% CI = 1.04 to 1.67) and reduced number of biopsy procedures by 49.3% while missing 7.2% GS ≥3 + 4 PC and 1.4% csPCa. Excluding men with negative Stockholm3 test reduced the number of MRI investigations at follow-up by 22.5% and biopsies by 56.8% while missing 6.9% GS ≥3 + 4 PC and 1.3% csPCa.

Conclusion: Including MRI and targeted/systematic biopsies in the follow-up for men on AS increased sensitivity of PC reclassification. Incorporation of risk prediction models including biomarkers may reduce the need for MRI use in men with low-risk PC.

Figure 1.

Flow chart STHLM3AS study.

Figure 2.

Comparison of biopsy strategies in terms of detection of Gleason score ≥ 3 + 4 cancers and csPCa defined as unfavorable intermediate risk PC or higher based on NCCN guidelines. Biopsy strategies evaluated: 1) systematic biopsy (SBx) in all men, 2) MRI-targeted biopsy (TBx) and SBx in all men, 3) MRI-TBx and SBx in MRI-positive, 4) MRI for Stockholm3-test positive men then MRI-TBx and SBx in MRI-positive men. Relative sensitivity was calculated as the sensitivity to detect cancer using 1 diagnostic strategy relative to the sensitivity of the reference strategy, systematic biopsies in all men. CI = confidence interval; csPCa = clinically significant prostate cancer, unfavorable intermediate risk or higher according to NCCN guidelines; GS = Gleason Score; MRI = magnetic resonance imaging; MRI (+) = MRI-positive (Prostate Imaging Reporting and Data System version 2 ≥ 3); PC = prostate cancer; RS = relative sensitivity; S3M (+) = Stockholm3-test percentage risk score > 10% of Gleason score ≥ cancer; SBx = systematic biopsy; TBx = MRI targeted biopsy; S3M = Stockholm3-test.