Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance

Abstract

Background

Active surveillance (AS) protocols rely on rectal examination, prostate-specific antigen, imaging, and biopsy to identify disease progression.

Objective

To evaluate whether an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies.

Design, setting, and participants

We identified a cohort of men initiated on AS between January 2013 and April 2016 at a single tertiary-care center. Patients completed confirmatory testing and prostate MRI prior to enrollment, then underwent laboratory and physical evaluation every 6 mo, MRI every 18 mo, and biopsy every 3 yr.

Outcome measurements and statistical analysis

MRI results were evaluated using composite Likert/Prostate Imaging Reporting and Data System v2 scoring. MRI and clinical changes were assessed for association with disease progression. Univariable and multivariable regression models were used to predict upgrading on 3-yr biopsy.

Results and limitations

At 3 yr, of 207 men, 66 (32%) had ≥ GG2 at biopsy: 55 (83%) with GG2, 10 (15%) with GG3, and one (1.5%) with GG4. Among patients with a 3-yr MRI score of ≥3, 41% had ≥ GG2 disease, compared with 15% with an MRI score of <3 (p = 0.0002). The MRI score increased in 48 men (23%), decreased in 27 (13%), and was unchanged in 132 (64%) men. Increases in MRI score were not associated with reclassification after adjusting for the 3-yr MRI score (p = 0.9). Biopsying only for an increased MRI score or clinical stage would avoid 681 biopsies per 1000 men, at the cost of missing ≥GG2 disease in 169 patients.

Conclusions

An AS strategy that uses MRI or clinical changes to trigger prostate biopsy avoids many biopsies but misses an unacceptable amount of clinically significant disease. Prostate biopsy for men on AS should be performed at scheduled intervals, regardless of stable imaging or examination findings.

Patient summary

An active surveillance strategy for biopsy based only on increases in magnetic resonance imaging score or clinical stage will avoid many biopsies; however, it will miss many patients with clinically significant prostate cancer.

Introduction

Active surveillance (AS) for men with low-risk prostate cancer is increasingly being adopted, and its use is universally endorsed in clinical guidelines [1], [2], [3], [4], [5]. Inherent in most AS protocols is the requirement to repeat prostate biopsy as part of a multimodal assessment, which includes physical examination, laboratory evaluation, and, increasingly, multiparametric magnetic resonance imaging (MRI) of the prostate [6]. Studies have shown that MRI is effective both in improving biopsy accuracy and in identifying disease progression for men on AS [7], [8]. Despite these improvements, scheduled systematic biopsy is still recommended in AS regimens to identify disease progression [9]. The role of changes identified during surveillance MRI, including detection of new lesions after confirmatory biopsy, has not been defined fully in the AS setting.

Less invasive methods to detect disease progression for men on AS can help reduce morbidity associated with scheduled systematic prostate biopsies. Despite advances in diagnostic technology, imaging and laboratory evaluations have yet to be proved sufficiently accurate to avoid a repeat prostate biopsy for men on AS without missing disease progression, and the European Association of Urology recommends a follow-up strategy based primarily on clinical and biopsy evaluation [9], [10], [11]. Several studies, however, have suggested that MRI stability can help identify men at low risk for disease reclassification and those in whom repeat biopsy can be avoided [12], [13], [14], [15]. Anecdotally, urologists are increasingly using negative or stable MRI findings to avoid performing repeat biopsy in men on AS. We reviewed our institutional experience of AS to evaluate disease progression in a contemporary cohort within a standardized AS program that involves regular physical examination, prostate-specific antigen (PSA) testing, multiparametric MRI, and biopsy follow-up. Our goals were twofold: to evaluate whether changes to MRI features or clinical stage identified using digital rectal examination (DRE) could be used to correctly identify disease progression among men with grade group (GG) 1 disease being treated on AS, and to identify the number of ≥ GG2 cancers potentially missed by implementing a biopsy protocol predicated only on changes in imaging or clinical stage compared with scheduled systematic biopsies, which is our institution’s standard of care.