Refers to Rouvière, O. et al. 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. Lancet Oncol. 20, 100–109 (2019).
The current standard for diagnosing prostate cancer is a transrectal ultrasonography (TRUS)-guided systematic biopsy. Unfortunately, ultrasonography lacks the capability to discriminate between benign and malignant prostate tissue and only confirms a systematic biopsy schema. Today, with the use of office-based MRI–TRUS software fusion biopsy platforms, many urologists advocate using multiparametric MRI (mpMRI)-guided targeted biopsy, as studies have suggested its superiority in detecting clinically significant cancer to the traditional standard of care1,2.
Table 1
Comparison of studies evaluating the role of MRI in biopsy-naive patients
Characteristic | PROMIS6 | PRECISION2 | MRI-FIRST7 |
|---|---|---|---|
Study design | Multicentre, prospective, paired-cohort, confirmatory | Multicentre, randomized, non-inferiority | Multicentre, prospective, paired-diagnostic |
Patients | • n = 576 | • n = 500 | • n = 251 |
• mpMRI and CBP | • 252 mpMRI arm; 248 TRUS biopsy arm | • mpMRI followed by TRUS and mpMRI-targeted biopsy | |
Eligibility | Biopsy-naive patients with clinical suspicion for prostate cancer | Biopsy-naive patients with clinical suspicion for prostate cancer | Biopsy-naive patients with clinical suspicion for prostate cancer |
Study goal | Evaluation of the diagnostic accuracy of mpMRI and TRUS biopsy | Prospective evaluation to demonstrate non-inferiority of mpMRI and targeted biopsy in the presence of an MRI-visible suspicious lesion compared with template TRUS biopsy | Prospective investigation of whether mpMRI and subsequent mpMRI-targeted biopsy improves detection and has the potential to omit TRUS biopsy |
Primary definition of clinically significant prostate cancera | Gleason ≥4 + 3 = 7 or cancer core length >6 mm | Gleason ≥3 + 4 = 7 | Gleason ≥3 + 4 = 7 |
Methodology | All eligible patients underwent 1.5T mpMRI (Index Test), followed by a CBP, such as a transperineal mapping biopsy (Test 2: core biopsies taken every 5 mm) followed by a TRUS biopsy (Test 3: 10–12 biopsy cores) | 1:1 randomization into: • mpMRI-targeted biopsy arm • TRUS biopsy arm: 10–12 biopsy cores | All eligible patients underwent 1.5T or 3T mpMRI followed by a TRUS biopsy (plus up to 2 cores from hypoechoic lesions) and mpMRI-targeted biopsy (up to 2 lesions with 3 cores per lesion) |
Study findings | Using mpMRI as a triage test: • 27% of primary biopsies could have been avoided • 5% reduction of clinically insignificant cancer detection • 18% increased detection of clinically significant cancer in mpMRI-directed TRUS biopsies | • Superiority of use of mpMRI before initial biopsy and mpMRI targeted biopsy compared with TRUS biopsy • mpMRI as a risk-assessment tool resulted in increased detection of clinically significant prostate cancer in the mpMRI arm (adjusted difference: +12% detection) and reduced detection of insignificant prostate cancer in the mpMRI arm (adjusted difference: −13% detection) | • mpMRI before biopsy improves detection • Additive value of combining biopsies • Omission of either biopsy modality would have missed clinically significant prostate cancer |
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The superiority of mpMRI-guided biopsy is unequivocally the case for the detection of anterior and apical tumours, which are frequently missed by TRUS biopsies. The role of mpMRI in detecting clinically significant cancer in patients who have undergone unsuccessful TRUS biopsies despite an elevated serum PSA level has been established3,4. Multidisciplinary MRI-guided prostate biopsy teams have further refined the technique and demonstrated a substantial improvement in accuracy for mpMRI-guided fusion biopsies5.
Despite the encouraging evidence of this practice in high-volume centres, the majority of data are derived from a patient population who had negative results on previous biopsy attempts using traditional TRUS biopsy techniques. The value of obtaining prebiopsy mpMRI in the biopsy-naive patient population is a major topic of interest, as the acquisition of mpMRI is most often recommended in patients with negative biopsy results4. To date, three prospective multicentre trials have evaluated prebiopsy mpMRI in biopsy-naive patient populations2,6,7 (Table 1).
The PROMIS trial6 was designed to assess the utility of mpMRI as a triage test in biopsy-naive patients with the goal of omitting a TRUS-guided systematic biopsy. Ahmed et al.6 compared the diagnostic accuracy of mpMRI and TRUS-guided biopsy using transperineal template prostate mapping as the reference standard. mpMRI had a significantly higher sensitivity value (93% versus 48%; McNemar test ratio 0.52; 95% CI 0.45–0.60) and negative predictive value (89% versus 74%, GEE model estimate for OR 0.34 (0.21–0.55); P < 0.0001) for predicting clinically significant prostate cancer (Gleason ≥4 + 3 or cancer core length ≥6 mm) in biopsy-naive patients . The authors proposed using mpMRI as a triage test before the first biopsy, as this practice has the advantage of increasing detection of clinically significant cancer (defined as ISUP grade ≥3 or maximum cancer core length >6 mm) while decreasing the detection of clinically insignificant cancer (defined as ISUP grade <3 or maximum cancer core length <6 mm).
The results of the PRECISION trial2 then supported those of the PROMIS study6. Biopsy-naive patients were randomized to either systematic extended sextant TRUS biopsy without the use of mpMRI, or prebiopsy mpMRI with subsequent biopsy only in the setting of a positive mpMRI (defined by having a PIRADS ≥3 lesion)2. The detection rate of clinically significant prostate cancer (defined as ISUP grade ≥2) was increased (P = 0.005), and the detection rate of clinically insignificant prostate cancer (ISUP grade = 1) was decreased (P < 0.001) in those assigned to prebiopsy mpMRI and targeted biopsy. These findings suggest the superiority of mpMRI-guided targeted biopsy in biopsy-naive patients, but critics of the study argue that the low detection rate of clinically insignificant cancer is caused by the study design, which avoids any biopsies in patients with negative mpMRI. As this trial design does not enable biopsy in men with negative mpMRI, the percentage of those patients with MRI-invisible cancer is not known.
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The trial by Rouvière et al.7 acknowledged the risk of underdetection of MRI-invisible lesions. The MRI-FIRST trial7 offered a prebiopsy mpMRI and both biopsy techniques to all participants rather than randomly assigning them to either biopsy technique7. The investigators demonstrated the additive value of systematic and targeted biopsy for detecting clinically significant prostate cancer when using the PRECISION trial criteria for clinically significant prostate cancer, defined as ISUP grade ≥2 (37.5%; 95% CI 31.4–43.8), whereas no difference in detection was found comparing systematic biopsy (29.9%; 95% CI 24.3–36.0) with mpMRI-targeted biopsy (32.3%; 95% CI 26.5–38.4). Interestingly, the added value of systematic biopsy was only marginal if the PROMIS trial definition for clinically significant cancers (defined as ISUP grade ≥3) was implemented (added value of systematic biopsy only 1.2%; 95% CI 0.2–3.5). As the definition of clinically significant prostate cancer and the need for intervention is debated among clinicians, the MRI-FIRST investigators summarized that the omission of systematic biopsy has no implication for the detection of ISUP grade group ≥3 tumours but has a risk of delayed or missed diagnosis for ISUP grade ≤2 cancers. The authors conclude that the use of mpMRI before biopsy of biopsy-naive patients increases the detection of clinically significant prostate cancer, but it does not preclude the need for a systematic biopsy. The limitations of this study include the lack of template prostate mapping biopsies as a reference standard as well as generalizability to the general urology community.
The investigators demonstrated the additive value of systematic and targeted biopsy
Collectively, these studies have affirmed the value of using mpMRI in the biopsy-naive patient population. However, adoption of mpMRI and targeted biopsy is in its infancy and the use of mpMRI and software-based fusion biopsy devices have multiple sources of possible errors that might result in clinically significant disease being missed8,9. Thus, urologists should have the choice as to whether to omit a systematic random biopsy. Urologists at centres with a dedicated, multidisciplinary team for prostate MRI fusion biopsy with many years of experience can use their clinical judgement and might feel comfortable in forgoing a systematic extended sextant biopsy in certain patients. However, not every institution has the expertise to forgo the systematic extended sextant biopsy.
these studies have affirmed the value of using mpMRI in the biopsy-naive patient population.
The ideal biopsy test would minimize the detection of clinically insignificant prostate cancer and simultaneously identify men who will benefit from intervention; however, we have not yet reached a state in which we can safely omit the current standard of care by obtaining a pre-biopsy MRI. Improved mpMRI quality, increased radiologist experience, improvements in the fusion biopsy devices, software advances and growing multidisciplinary experience in the urological community have enabled improved prostate cancer detection and adoption of mpMRI into the urologists’ armamentarium10. We recommend the inclusion of a systematic biopsy at this time until the full adoption of this modality occurs in the general urology community.
Competing interests
The NIH and Philips have a Cooperative Research and Development Agreement. The NIH has intellectual property in the field, including among other patents and patent applications, Patent: “System, methods, and instrumentation for image guided prostate treatment” US Patent number: 8948845, with inventors/author P.A.P. The NIH and Philips (InVivo Inc) have a licensing agreement. The NIH and authors receive royalties for a licensing agreement with Philips/InVivo Inc. The NIH does not endorse or recommend any commercial products, processes or services. The views and personal opinions of the authors expressed herein do not necessarily state or reflect those of the US Government, nor reflect any official recommendation nor opinion of the NIH nor the National Cancer Institute.