Elsevier

The Lancet Oncology

Volume 20, Issue 1, January 2019, Pages 100-109
The Lancet Oncology

Articles
Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study

https://doi.org/10.1016/S1470-2045(18)30569-2Get rights and content

Summary

Background

Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients.

Methods

In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18–75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants.

Findings

Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3–36·0) and targeted biopsy (32·3%, 26·5–38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8–8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6–11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria).

Interpretation

There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy.

Funding

French National Cancer Institute.

Introduction

Multiparametric MRI has excellent sensitivity for detecting prostate cancer classified as grade group 2 or higher, according to the International Society of Urological Pathology (ISUP),1, 2 and is increasingly used to locate suspicious lesions before biopsy.3 Most guidelines recommend pre-biopsy multiparametric MRI in patients with a history of negative biopsy and persistent suspicion of prostate cancer.4, 6 However, whether pre-biopsy multiparametric MRI should be performed in biopsy-naive patients remains unclear.3, 7, 8, 9

Two aspects should be considered when assessing the role of multiparametric MRI in biopsy-naive patients. The first is the improvement in detection of clinically significant prostate cancer—ie, the added value of biopsies targeting lesions identified by MRI, compared with the classical diagnostic pathway that uses systematic biopsy. The second is the added value of systematic biopsy in prostate areas that appear normal on multiparametric MRI.

Results from two prospective multicentre studies have clarified these matters. In the PRECISION study,10 500 biopsy-naive patients were randomly assigned to either systematic biopsy without multiparametric MRI, or to multiparametric MRI with targeted biopsy only (in the case of positive multiparametric MRI) or no biopsy (in the case of negative multiparametric MRI). The detection of ISUP grade group 2 or higher cancers was significantly higher in men assigned to multiparametric MRI and targeted biopsy (38%) than in those assigned to systematic biopsy (26%; adjusted difference 12 percentage points, 95% CI 4–20, p=0·005). However, this study did not investigate whether combining systematic biopsy and targeted biopsy could increase detection of clinically significant prostate cancer. The PROMIS study11 assessed multiparametric MRI and systematic biopsy against template prostate mapping biopsy in 576 biopsy-naive men. The negative predictive value of multiparametric MRI was 89% (95% CI 83–94) for clinically significant prostate cancer, defined as ISUP grade group 3 or higher cancers or those with a maximum cancer core length (MCCL) of 6 mm or longer. However, the negative predictive value was 76% (69–82) for ISUP grade group 2 or higher cancers.11 This suggests that targeted biopsy alone might not provide optimal detection of ISUP grade group 2 or higher cancers, and that systematic biopsy might still detect some clinically significant prostate cancers that are missed by targeted biopsy.

Research in context

Evidence before this study

We searched PubMed for publications in English or French using the search terms “prostate cancer”, “MRI”, “prostate biopsy”, “systematic biopsy”, and “targeted biopsy”. When MRI-FIRST was designed in 2013, no prospective randomised trials had compared systematic and targeted biopsy in biopsy-naive patients. At least three systematic reviews, published in 2014 and 2015, suggested that targeted biopsy detected more clinically significant prostate cancer than did systematic biopsy. However, one of these reviews showed that the improvement in detection of clinically significant prostate cancer because of targeted biopsy was substantial in patients with a history of negative biopsy, but was only marginal in biopsy-naive men. At least five prospective single-centre randomised trials, published between 2015 and 2017, gave contradictory results regarding whether targeted biopsy could improve detection of clinically significant prostate cancer in biopsy-naive patients. The prospective multicentre PROMIS study, published in 2017, assessed multiparametric MRI and systematic biopsy against template prostate mapping biopsy in biopsy-naive men and showed that multiparametric MRI was significantly more sensitive than systematic biopsy in detecting clinically significant prostate cancer, defined as International Society of Urocological pathology (ISUP) grade group 3 or higher tumours, or tumours with maximum cancer core length of at least 6 mm. The prospective multicentre PRECISION study, published in 2018, randomly assigned biopsy-naive men to either systematic biopsy without multiparametric MRI or to pre-biopsy multiparametric MRI with no biopsy if the multiparametric MRI was negative, and only to targeted biopsy if the multiparametric MRI was positive. The detection rate of ISUP grade group 2 or higher tumours was significantly higher in men assigned to multiparametric MRI and targeted biopsy than in those assigned to systematic biopsy. By contrast, the detection of clinically insignificant tumours (ISUP grade group 1 tumours) was significantly higher in patients assigned to systematic biopsy.

Added value of this study

Rather than randomly assigning patients to either systematic or targeted biopsy, we chose to do both biopsy techniques in the same biopsy-naive men. This approach allowed us to separately investigate the added value of systematic and targeted biopsy by analysing discordant pairs. The results of this study nuance the results of the PRECISION trial. Indeed, we found that both systematic and targeted biopsy had substantial added value in detecting ISUP grade group 2 or higher tumours since a third of these were detected by only one biopsy technique. The added value of systematic biopsy was marginal only for the detection of ISUP grade group 3 or higher tumours. Similar to the PRECISION trial, targeted biopsy in MRI-FIRST detected significantly fewer low-volume, low-grade tumours than did systematic biopsy.

Implications of all the available evidence

Findings from both the MRI-FIRST and PRECISION trials suggest that multiparametric MRI could be safely used as a triage test for the detection of ISUP grade group 3 or higher cancers, and that targeted biopsy has added value in the detection of ISUP grade group 2 or higher cancers. The use of targeted biopsy alone could decrease the detection of non-significant prostate cancer, but the added value of systematic biopsy could still be substantial for the detection of ISUP grade group 2 or higher cancers, which might be optimised when both approaches are combined. Further research is needed to assess the influence of the number of targeted cores on targeted biopsy accuracy, which was lower (on average) in MRI-FIRST than in the PRECISION trial.

We present the results of the MRI-FIRST trial, a prospective multicentre study in biopsy-naive patients that compared, in the same patients, the detection of ISUP grade group 2 or higher cancers, obtained by 12–14 core systematic biopsy and 3–6 core targeted biopsy.

Section snippets

Study design and participants

The study was done in 16 centres in France (11 university hospitals, two cancer centres, and three private hospitals) that were experienced in prostate multiparametric MRI and biopsy (appendix p 3). Participants were recruited in outpatient clinics by local urologists, among patients referred for suspicion of prostate cancer on the basis of increased prostate-specific antigen concentration, abnormal digital rectal examination, or family history of prostate cancer. Eligible men had no history of

Results

Between July 15, 2015, and Aug 11, 2016, 275 men were enrolled. After the exclusion of 24 (9%) patients from the analysis (figure), central reading results for systematic biopsy and targeted biopsy were available for 251 patients (table 1), including 27 patients with protocol deviations (figure).

36 (14%) patients had no lesions on multiparametric MRI (table 1). In the remaining 215 patients, 321 lesions were described; the Likert and PI-RADSv2 scores would have yielded a concordant biopsy

Discussion

In MRI-FIRST, detection of csPCa-A did not differ between targeted biopsy and systematic biopsy. Detection of csPCa-B also did not differ between the two biopsy methods. For detection of csPCa-A and csPCa-B, detection improved when both systematic and targeted biopsy were combined. Detection of csPCa-C was significantly lower with systematic biopsy than with targeted biopsy, and targeted biopsy detected significantly fewer non-clinically significant prostate cancer tumours than did systematic

Data sharing

Individual participant data will be available (including data dictionaries). Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figure, and appendices), will be shared. The study protocol, statistical analysis plan, and analytical code will also be available. Data will be available between 9 and 36 months after Article publication. Data may be shared with investigators whose proposed use of the data has been approved by an

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All MRI-FIRST investigators are listed in the appendix

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