Lucas W. Dean, MD
Karim Touijer, MD, MPH
Simultaneously presented at the 2018 European Association of Urology meeting and published in The New England Journal of Medicine, the PRECISION trial will go down as a landmark study for solidifying the role of magnetic resonance imaging (MRI) in prostate cancer diagnosis.1 This trial provides level 1 evidence that the use of MRI—with or without subsequent targeted biopsy—is superior to standard 10- to 12-core biopsy for the detection of clinically significant prostate cancer. Secondarily, the MRI with or without targeted biopsy strategy more than halved the number of Grade Group 1 prostate cancer diagnoses and resulted in fewer adverse events. These findings are consistent with the goals of contemporary prostate cancer early detection: to find the “bad actors” while minimizing overdetection of indolent disease.
Closer Look at PRECISION Results
PRECISION was originally designed to show that MRI with or without targeted biopsy was noninferior to standard transrectal ultrasonography (TRUS)-guided biopsy for the detection of clinically significant prostate cancer. PRECISION was powered for a noninferiority margin of 5%, deeming that any lesser difference in cancer detection rates would be unimportant. Sample size calculations were based upon estimates of clinically significant cancer rates of 40% in the MRI with or without targeted biopsy arm and 30% in the standard-biopsy arm.
Compared with population-based reports of overall positive biopsy rates ranging from 33% to 50%,2,3 this estimate of 40% detection of Gleason score ≥ 3 + 4 prostate cancer might seem unprecedentedly high. An overestimate of the detection rate predicted in the MRI with or without targeted biopsy arm would have rendered a smaller sample size calculation. Fortuitously, the authors’ predictions for clinically significant cancer detection turned out to be remarkably close to what was observed (38% for MRI with or without targeted biopsy vs 26% for standard biopsy), allowing them to demonstrate superiority within the context of a noninferiority trial design.
As pragmatic and generalizable as the results of PRECISION appear, they were still achieved within the context of a randomized trial, and the successful diffusion of this approach on the population level is not guaranteed.— LUCAS W. DEAN, MD, AND KARIM TOUIJER, MD, MPH
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PRECISION was a remarkably well-conceived study. The design was pragmatic, and the study enrolled patients from numerous academic and nonacademic sites across 11 countries. Imaging and biopsy techniques were variable and reflected what individual centers and operators had available to them. A total of 23 different permutations of MRI models, field strengths, coils, and sequences performed are described in the supplementary appendix. Both visual- and software-assisted fusion techniques were utilized, and the MRI-targeted biopsy operators were understandably less experienced than the standard biopsy operators. MRI-targeted biopsies were limited to 3 areas suspicious for prostate cancer, with up to 4 cores from each, to a maximum of 12 biopsy cores for each participant. It is important to note the results achieved were realized with a median of only four cores in the MRI-targeted arm.
Questions Emerge
Impressive as PRECISION’s results may be, two main questions emerge from the diagnostic approach used in the study. First, what becomes of the 28% of men in the MRI with or without targeted biopsy arm who did not warrant a biopsy of any kind? The appropriate frequency of clinical, biochemical, and imaging follow-up remains to be defined. Surely, the MRI with or without targeted biopsy strategy could miss a small number of “significant” cancers among men with PI-RADS (Prostate Imaging–Reporting and Data System) version 2 scores of 1 and 2. That stated, we have been getting by for decades despite the imperfections of systematic biopsy. Data from the Danish Cancer Registry exemplify this, showing the 20-year risk of prostate cancer–specific mortality after a benign initial biopsy (in many cases, only 6- or 10-core) is a near-negligible 5%.4
Without long-term outcomes data, the negative predictive value of the MRI-guided strategy can only be reported in terms of the biopsy pathology. It is increasingly clear that the pathologic definition of clinically significant prostate cancer is not synonymous with the actual risk of prostate cancer–specific mortality. For instance, in the PROMIS study, 53% of men harbored clinically significant disease on transperineal mapping biopsy when the same definition used in PRECISION was applied (Gleason score ≥ 3 + 4).5 Contrast this to the ProtecT trial, in which active monitoring patients (albeit enriched with grade group 1 disease) enjoyed a 98.8% prostate cancer–specific survival rate at 10 years.6 The MRI with or without targeted biopsy approach is not perfect, but it is unlikely to be dangerous.
These findings are consistent with the goals of contemporary prostate cancer early detection: to find the ‘bad actors’ while minimizing overdetection of indolent disease.— LUCAS W. DEAN, MD, AND KARIM TOUIJER, MD, MPH
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Second, how will we roll out this new paradigm in the real world? It has been estimated that over one million prostate biopsies are performed annually in the United States,7 although this number may have fallen since the 2012 U.S. Preventive Services Task Force recommendation against prostate-specific antigen screening.8,9 Although an MRI-guided strategy might further reduce the number of biopsies performed, significant challenges remain to its widespread implementation, and they have only been partially addressed in published cost-effectiveness models that favor this approach.10,11 Adequate training of urologist and radiologists, quality control, and the expansion of the physical infrastructure are all required. As pragmatic and generalizable as the results of PRECISION appear, they were still achieved within the context of a randomized trial, and the successful diffusion of this approach on the population level is not guaranteed.
Many have construed the results of PRECISION as practice-changing. Although challenges exist, at a minimum they are practice-affirming for many U.S. academic medical centers that have already incorporated MRI into their diagnostic algorithm for prostate cancer. The authors should be congratulated for their work in transforming the way we diagnose prostate cancer—and in just 2 short years from the date of trial opening.
DISCLOSURE: Drs. Dean and Touijer reported no conflicts of interest.
REFERENCES
1. Kasivisvanathan V, Rannikko AS, Borghi M, et al: MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med 378:1767-1777, 2018.
2. Kapoor DA, Bostwick DG, Mendrinos SE, et al: Utilization trends and positive biopsy rates for prostate biopsies in the United States: 2005 to 2011. Rev Urol 15:137-144, 2013.
3. Welch HG, Fisher ES, Gottlieb DJ, et al: Detection of prostate cancer via biopsy in the Medicare-SEER population during the PSA era. J Natl Cancer Inst 99:1395-1400, 2007.
4. Klemann N, Røder MA, Helgstrand JT, et al: Risk of prostate cancer diagnosis and mortality in men with a benign initial transrectal ultrasound-guided biopsy set: A population-based study. Lancet Oncol 18:221-229, 2017.
5. Ahmed HU, El-Shater Bosaily A, Brown LC, et al: Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet 389:815-822, 2017.
6. Hamdy FC, Donovan JL, Lane JA, et al: 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 375:1415-1424, 2016.
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8. Jemal A, Fedewa SA, Ma J, et al: Prostate cancer incidence and PSA testing patterns in relation to the USPSTF screening recommendations. JAMA 314:2054-2061, 2015.
9. Halpern JA, Shoag JE, Artis AS, et al: National trends in prostate biopsy and radical prostatectomy volumes following the US Preventive Services Task Force Guidelines against prostate-specific antigen screening. JAMA Surg 152:192-198, 2017.
10. Faria R, Soares MO, Spackman E, et al: Optimising the diagnosis of prostate cancer in the era of multiparametric magnetic resonance imaging: A cost effectiveness analysis based on the Prostate MR Imaging Study (PROMIS). Eur Urol 73:23-30, 2018.
11. Walz J: The ‘PROMIS’ of magnetic resonance imaging cost effectiveness in prostate cancer diagnosis? Eur Urol 73:31-32, 2018.
