Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up

doi:10.1016/j.eururo.2019.10.007

European Urology

Volume 77, Issue 3, March 2020, Pages 311-317

https://doi.org/10.1016/j.eururo.2019.10.007 Get rights and content

Abstract

Background

The initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis.

Objective

To determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not.

Design, setting, and participants

This is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling.

Outcome measurements and statistical analysis

Patients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2.

Results and limitations

In total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p =  0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p =  0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p =  0.019).

Conclusions

Baseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates.

Patient summary

The ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance.

This study is registered at ClinicalTrials.gov (NCT01354171).

Introduction

Active surveillance (AS) has become a standard of care for most men with low-grade prostate cancer on the basis of multiple large mature cohorts demonstrating its safety [1]. It has been adopted in national guidelines throughout the world [2], [3], [4]. An important limitation of conservative management is the significant proportion of patients diagnosed with Gleason grade group 1 (GG 1) cancer who harbor more aggressive but potentially curable disease [4].

Early identification of these occult cancers via magnetic resonance imaging (MRI) offers the appeal of improving surveillance outcomes by allowing those with coexistent aggressive disease to be identified and treated in a more timely fashion [5]. An additional potential benefit of incorporating MRI would be the avoidance of frequent systematic biopsy (SBx) if the MRI is negative and has a sufficiently high negative predictive value (NPV) for significant cancer [6], [7], [8], [9].

The ASIST study was initiated to evaluate the effectiveness of MRI targeted biopsies versus conventional SBx in identifying higher-grade prostate cancer in men on AS. The primary endpoint of the study was the proportion of subjects whose confirmatory biopsy was upgraded to GG ≥ 2 in targeted versus SBx. The hypothesis was that targeted biopsies would identify as many or more men with GG ≥ 2 cancer than SBx. Results were reported previously [10]. The key observations were that there was no statistically significant difference between the two arms; 23% of patients in the SBx group had GG ≥ 2 cancer at the time of confirmatory biopsy, compared to 21% of patients in the MRI arm (targeted + SBx). Statistically significant differences in upgrading rates were seen among the three centers.

All patients with a negative biopsy or GG 1 disease at the time of confirmatory biopsy who continued on AS were requested to have MRI and repeat (third) biopsy at the 2-yr time point. Here we report the follow-up results.

Section snippets

Patients and methods

The design of the trial was previously reported [10]. In brief, ASIST was a prospective, multicenter, randomized, open-label trial for men with a diagnosis of low-risk prostate cancer within the last year being managed with AS. Subjects were stratified by center, serum prostate-specific antigen (PSA) at study entry (<5.0 or >5.0 to <10.0 ng/ml), and age at study entry (<65 vs >65 yr). After stratification, patients were randomized in a 1:1 ratio to either SBx or MRI with both targeted and SBx.

Results

Between December 2011 and December 2015, 296 patients were enrolled in the study. Of those registered, 23 patients were excluded before randomization, leaving a total of 273 randomized patients. Reasons for exclusion are listed in Fig. 1. On randomization, 136 patients were randomized to the SBx arm and 137 to the MRI arm. No obvious differences between intervention arms in terms of stratum, demographics, tumor characteristics, or prior treatments were noted.

Discussion

The initial results from the ASIST trial did not show an increase in upgrading with the addition of MRI and targeted biopsies to systematic biopsies. These data were at odds with the experience reported by other groups for men at risk of prostate cancer. In the PROMIS trial [14], MRI was substantially more sensitive than TRUS biopsy for significant cancer (93% vs 48%; p <  0.0001). In the PRECISION trial [15], in which patients in the MRI arm only underwent targeted biopsies, clinically

Conclusions

The 2-yr follow-up for this cohort revealed a lower rate of upgrading and a 50% reduction in the rate of AS failure in the MRI cohort compared to the SBx group, reinforcing the value of MRI and targeted biopsy in the management of men on AS.

Author contributions: Laurence Klotz had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Klotz, Pond, Loblaw, Haider.

Acquisition of data: Klotz,

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Platinum Priority – Prostate CancerEditorial by XXX on pp. x–y of this issue.Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up

Abstract

Background

Objective

Design, setting, and participants

Outcome measurements and statistical analysis

Results and limitations

Conclusions

Patient summary

Introduction

Section snippets

Patients and methods

Results

Discussion

Conclusions

J Urol

J Urol

J Urol

Eur Urol

Eur Urol Oncol

J Urol

Lancet

Platinum Priority – Prostate Cancer
Editorial by XXX on pp. x–y of this issue.
Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up