Diagnostic accuracy of multi-parametric MRI and transrectal ultrasound-guided biopsy in prostate cancer
Authors: James E Thompson, Phillip D Stricker
Journal: The Lancet (2017)

Recent randomised controlled trials of prostate cancer screening and treatment have reported disappointing results. PLCO1Andriole GL Crawford ED Grubb RL et al.Mortality results from a randomized prostate-cancer screening trial.N Eng J Med. 2009; 360: 1310-1319Crossref PubMed Scopus (2369) Google Scholar failed to demonstrate a benefit for population-based prostate-specific antigen (PSA) screening, while ERSPC2Schroder FH Hugosson J Roobol MJ et al.Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.Lancet. 2014; 384: 2027-2035Summary Full Text Full Text PDF PubMed Scopus (1049) Google Scholar reported a survival benefit, but 781 men needed to be invited for screening and 27 diagnosed with cancer to prevent one death. Furthermore, the PIVOT3Wilt TJ Brawer MK Jones KM et al.Radical prostatectomy versus observation for localized prostate cancer.N Eng J Med. 2012; 367: 203-213Crossref PubMed Scopus (1453) Google Scholar (2012) and ProtecT4Hamdy FC Donovan JL Lane JA et al.10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer.N Eng J Med. 2016; 375: 1415-1424Crossref PubMed Scopus (1710) Google Scholar (2016) studies investigated treatment versus observation for localised PSA-detected prostate cancer and reported no mortality benefit for treatment over observation. Novel diagnostic tests with higher discriminative abilities for aggressive prostate cancer are therefore urgently needed. Multi-parametric MRI might be used as a second-line diagnostic tool in men with abnormal PSA or digital rectal examination to improve selection for biopsy. In The Lancet, Hashim U Ahmed and colleagues report the PROMIS study,5Ahmed HU El-Shater Boaily A Brown LC et al.the PROMIS study groupDiagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study.Lancet. 2017; (published online Jan 19.)http://dx.doi.org/10.1016/S0140-6736(16)32401-1Summary Full Text Full Text PDF Scopus (1742) Google Scholar which aimed to determine the accuracy of multi-parametric MRI for detecting intermediate-risk and high-risk prostate cancer, using a highly robust reference test: 5mm grid-template transperineal biopsy with 60–70 cores (TTMB) + 12-core transrectal ultrasound-guided biopsy (TRUSB). They reported a high sensitivity (93%) and moderate specificity (41%). The study design and results are similar to our study6Thompson JE van Leeuwen PJ Moses D et al.The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer.J Urol. 2016; 195: 1428-1435Summary Full Text Full Text PDF PubMed Scopus (108) Google Scholar of 388 men in which we performed 30-core TTMB as the reference test and reported sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52% for MRI. Although the primary objective of PROMIS was to determine the accuracy of MRI, on secondary endpoint analysis, MRI was compared to TRUSB (using TTMB as the reference test) and was more sensitive (93% vs 48%, p<0·001). Although the sensitivity of TRUSB might have been compromised by performing it after TTMB, these results are consistent with those of Pokorny and colleagues7Pokorny MR de Rooij M Duncan E et al.Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies.Eur Urol. 2014; 66: 22-29Summary Full Text Full Text PDF PubMed Scopus (427) Google Scholar who compared sensitivity of in-gantry MRI-biopsy (92%) to TRUSB (70%) and Siddiqui and colleagues8Siddiqui MM Rais-Bahrami S Turkbey B et al.Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer.JAMA. 2015; 313: 390-397Crossref PubMed Scopus (1136) Google Scholar who compared MRI-US fusion biopsy (77% sensitivity) to TRUSB (53%). Due to the methodological limitations of performing targeted biopsy or TTMB and TRUSB in the same patient, several randomised controlled trials are now underway that compare MRI-targeted biopsy against TRUSB. This study adds considerable weight to the literature because of its large sample size (thereby increasing precision of accuracy estimates), the multi-centre design with variable prostate MRI expertise (which increases the generalisability of the findings), use of advanced cancer defined by grade and volume as the endpoint (increasing the clinical utility of accuracy estimates), and—perhaps most importantly—use of a highly reliable reference test. Although too invasive for routine clinical use, TTMB + TRUSB provides a near ideal reference test given that radical prostatectomy cannot ethically be performed in men without significant cancer findings on biopsy. The high sensitivities reported in both PROMIS9Futterer JJ Briganti A De Visschere P et al.Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature.Eur Urol. 2015; 68: 1045-1053Summary Full Text Full Text PDF PubMed Scopus (581) Google Scholar and our study6Thompson JE van Leeuwen PJ Moses D et al.The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer.J Urol. 2016; 195: 1428-1435Summary Full Text Full Text PDF PubMed Scopus (108) Google Scholar (the two largest studies to date, with 576 and 388 men respectively) suggests that the lower estimates in previous meta-analyses9Futterer JJ Briganti A De Visschere P et al.Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature.Eur Urol. 2015; 68: 1045-1053Summary Full Text Full Text PDF PubMed Scopus (581) Google Scholar, 10de Rooij M Hamoen EH Futterer JJ Barentsz JO Rovers MM Accuracy of multiparametric MRI for prostate cancer detection: a meta-analysis.A J Roentgenol. 2014; 202: 343-351Crossref PubMed Scopus (344) Google Scholar might be influenced by confounding factors such as small sample size, use of radical prostatectomy as the reference test, and use of any cancer as the endpoint definition. Ahmed and colleagues demonstrate that MRI could reduce biopsies, and overdetection and underestimation of high-risk tumours (eg, anterior tumours missed by TRUSB). The recently reported ProtecT multi-centre trial4Hamdy FC Donovan JL Lane JA et al.10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer.N Eng J Med. 2016; 375: 1415-1424Crossref PubMed Scopus (1710) Google Scholar provides further impetus for a change to more selective biopsy: at 10-years median follow-up in 1643 men, prostate cancer-specific mortality was very low (1%) with no difference between surveillance, surgery, and radiation arms, suggesting high overdetection and overtreatment rates. Conversely, 21% of men with low risk disease who underwent surveillance experienced progression (local symptoms or metastases), implying that harm was caused by undertreatment. The ProtecT results will therefore further fuel criticisms that PSA screening and TRUSB perform poorly for selectively detecting aggressive tumours that require radical treatment and for risk-stratifying men. In our view the solution is not to abandon prostate cancer screening altogether, but rather to improve it by adding the anatomic and functional information provided by MRI and the biologic information provided by genetic tools such as Stockholm-3,11Gronberg H Adolfsson J Aly M et al.Prostate cancer screening in men aged 50–69 years (STHLM3): a prospective population-based diagnostic study.Lancet Oncol. 2015; 16: 1667-1676Summary Full Text Full Text PDF PubMed Scopus (258) Google Scholar Oncotype Dx,12Klein EA Cooperberg MR Magi-Galluzzi C et al.A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.Eur Urol. 2014; 66: 550-560Summary Full Text Full Text PDF PubMed Scopus (446) Google Scholar Decipher,13Cooperberg MR Davicioni E Crisan A Jenkins RB Ghadessi M Karnes RJ Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort.Eur Urol. 2015; 67: 326-333Summary Full Text Full Text PDF PubMed Scopus (155) Google Scholar and others into predictive nomograms that guide selection for biopsy and active surveillance. This approach might reduce overdetection, overtreatment and undertreatment, thus improving oncologic, quality of life, and cost-efficiency outcomes for the population. Future research should be devoted to developing such models and assessing their utility in terms of decision making and cost-benefit. We declare no competing interests. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory studyUsing MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. Full-Text PDF Open Access