Dataset Information

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.

SUBMITTER: Olsson H

PROVIDER: S-EPMC8096373 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceTransrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance.ObjectiveTo evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance.Design, settings, and participantsThis retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017.ExposuresAll confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment.Main outcomes and measuresThe primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome.ResultsOf 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy.Conclusions and relevanceThe findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.

Project description:BackgroundAlthough the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts.ObjectiveWe describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring.Design, setting, and participantsData on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database.Outcome measurements and statistical analysisPrimary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer-related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected.Results and limitationsMore than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37-82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0-87.6) and 71.8% (95% CI: 68.2-75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4-5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p < 0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1-9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0-4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2-11.3).ConclusionsThe rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk.Patient summaryIn this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours.