Diagnostic performance of MRI targeted prostate biopsy. A metanalysis
Currently the standard procedure to perform a prostate biopsy involves taking 12 cores; this type of approach is traditionally characterized by poor sensitivity with high rate of false negatives. Different strategies, such as repeat biopsy or different biopsy template, have been used to minimize false negative (repeat biopsy, saturation biopsy), but all these techniques, while add some diagnostic elements, remain dependent on random sampling.
Magnetic resonance (MRI) indeed offers the potential to improve prostate cancer diagnosis, providing superior resolution of anatomical structures and anatomical landmark such as prostate capsule, comparing to transrectal ultrasound(TRUS). Particularly multiparametric MRI has been demonstrated to have a high accuracy in detecting suspected foci of prostate cancer. As a consequence MRI targeted biopsy has been advocated as an innovative tool for the diagnosis of prostate cancer with the aim to avoid unnecessary biopsy, unnecessary prostate puncture during the biopsy (limiting the risk of complications) while obtaining a high prostate cancer detection.
We performed a meta-analysis of the literature with the intention to assess the diagnostic performance of MRI targeted prostate biopsy
Methods and results
After the definition of the clinical question a systematic literature search was conducted through MEDLINE. The search keys were “magnetic resonance prostate biopsy 3d” and “magnetic resonance prostate biopsy fusion”. The search was limited to the last ten years, and papers in English language. The search was performed the 28th December of 2012. A total of 153 papers were found. One hundred eleven were considered not adequate from the title, 20 from the abstract and 10 from the full text. Eleven papers were finally selected [3-13] accounting for twelve dataset (the paper from Portalez examines two different populations, respectively training and validation set). Five studies [5,7,8,9,13] were excluded because it was impossible to extract the complete dataset necessary to perform the metanalysis (number of true positive, true negative, false positive and false negative cases). The remaining 6 studies were assessed by means of Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool  According to QUADAS, the paper from Portalez was considered at high risk of bias and was excluded from the final analysis. We create a 2 x 2 contingency table (true-positive (TP), false- positive (FP), false-negative (FN), and true-negative (TN)) and call TP when prostate cancer was present in the biopsy specimen and in the radiology pattern. We create a database including study reference, TP, TN, FP, FN value and specificity and sensibility.
The heterogeneity of the studies examined in regard to patients characteristics, dimension of the population, technology employed and methodology conducted was really elevated. Therefore fixed and random effects model for the metanalysis were both used. The fixed effects model was preferred to assess a single effect which is common to all studies (positive or negative likelihood diagnostic ability of MRI targeted biopsy). The random effects model indeed takes into account for the elevated heterogeneity of the studies. Results from both analysis were summarized to allow for the identification of discrepancies.
The entry criteria were highly heterogeneous among the studies examined and can be only summarized in individuals with suspected or known prostate cancer.
Three [1,2,9] of the 5 studies included were retrospective analysis of case series whereas 2 were prospective [4,10].
Four studies refers to the biopsy findings in the individual [1,2,4,9] and 1 in the single core  to assess the diagnostic performance.
In regard to MRI power, coil, sequence, biopsy type, scheme and type of the studies the data were summarized in table 3
The one by one analysis of the paper evidences an extreme variability in regard to sensitivity, range 0.39 – 0.93, specificity, range 0.16 – 0.921 and positive predictive value, range 0.18 – 0.71.
As expected both fixed and random effects model gave similar results. The metanalysis was flawed by an elevated inconsistency ratio for sensitivity and specificity and positive likelihood ratio. Indeed the negative predictive value is always elevated in regard to the reference standard, ranging from 0.65 to 0.97. Accordingly the resulting heterogeneity test was not significant and the inconsistency ratio equal to zero in both models.
Globally the performance of the MRI guided prostate biopsy in combination with a random scheme can be finally summarized by the odds ratio meta analysis. Particularly the pooled odds ratio was 4.061 (95% CI 2.847 – 5.792) and 4.475 (95% CI 2.384 – 8.401) respectively in the fixed and random effects models.
Even if the heterogeneity test was slightly significant (p 0.038) and the inconsistency little above the 50% cut off in both models, the diagnostic performance should be considered clinically relevant especially thanks to the contribute of negative predictive ability. Given the high cost of the MRI targeted biopsy, it is therefore the ideal procedure in cases with multiple negative biopsies and persistent suspicion of cancer or during active surveillance of known prostate cancer. Particularly biopsy could be postponed in patients with a negative MRI whereas in cases with a positive MRI, the biopsy could be theoretically limited to targeted puncture of the prostate limiting the risk of complications.
1) Perdonà S, Di Lorenzo G, Autorino R, Buonerba C, De Sio M, Setola SV, Fusco R, Ronza FM, Caraglia M, Ferro M, Petrillo A. Combined magnetic resonance spectroscopy and dynamic contrast-enhanced imaging forprostate cancer detection. Urol Oncol. 2011 Sep 7
2) Hadaschik BA, Kuru TH, Tulea C, Rieker P, Popeneciu IV, Simpfendörfer T, Huber J, Zogal P, Teber D, Pahernik S, Roethke M, Zamecnik P, Roth W, Sakas G, Schlemmer HP, Hohenfellner M. A novel stereotactic prostate biopsy system integrating pre-interventional magnetic resonance imaging and live ultrasound fusion. J Urol. 2011 Dec;186(6):2214-20. doi: 10.1016/j.juro.2011.07.102. Epub 2011 Oct 19.
3) Hambrock T, Fütterer JJ, Huisman HJ, Hulsbergen-vandeKaa C, van Basten JP, van Oort I, Witjes JA, Barentsz JO. Thirty-two-channel coil 3T magnetic resonance-guided biopsies of prostate tumor suspicious regions identified on multimodality 3T magnetic resonance imaging: technique and feasibility. Invest Radiol. 2008 Oct;43(10):686-94. doi: 10.1097/RLI.0b013e31817d0506.
4) Hara T, Inoue Y, Satoh T, Ishiyama H, Sakamoto S, Woodhams R, Baba S, Hayakawa K. Diffusion-weighted imaging of local recurrent prostate cancer after radiation therapy: comparison with 22-core three-dimensional prostate mapping biopsy. Magn Reson Imaging. 2012 Oct;30(8):1091-8. doi: 10.1016/j.mri.2012.04.022. Epub 2012 Jul 21.
5) Mouraviev V, Pugnale M, Kalyanaraman B, Verma S, Zhai QJ, Gaitonde K, Donovan JF. The feasibility of multiparametric magnetic resonance imaging for targeted biopsy using novel navigation systems to detect early stage of prostate cancer: The preliminary experience. J Endourol. 2012 Sep 11.
6) Natarajan S, Marks LS, Margolis DJ, Huang J, Macairan ML, Lieu P, Fenster A. Clinical application of a 3D ultrasound-guided prostate biopsy system. Urol Oncol. 2011 May-Jun;29(3):334-42
7) Pinto PA, Chung PH, Rastinehad AR, Baccala AA Jr, Kruecker J, Benjamin CJ, Xu S, Yan P, Kadoury S, Chua C, Locklin JK, Turkbey B, Shih JH, Gates SP, Buckner C, Bratslavsky G, Linehan WM, Glossop ND, Choyke PL, Wood BJ. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol. 2011 Oct;186(4):1281-5. doi: 10.1016/j.juro.2011.05.078.
8) Portalez D, Mozer P, Cornud F, Renard-Penna R, Misrai V, Thoulouzan M, Malavaud B. Validation of the European society of urogenital radiology scoring system for prostate cancer diagnosis on multiparametric magnetic resonance imaging in a cohort of repeat biopsy patients. Eur Urol. 2012 Dec;62(6):986-96.
9) Sonn GA, Natarajan S, Margolis DJ, Macairan M, Lieu P, Huang J, Dorey FJ, Marks LS. Targeted biopsy in the detection of prostate cancer using an office based magnetic resonance ultrasound fusion device. J Urol. 2013 Jan;189(1):86-92.
10) Turkbey B, Xu S, Kruecker J, Locklin J, Pang Y, Bernardo M, Merino MJ, Wood BJ, Choyke PL, Pinto PA. Documenting the location of prostate biopsies with image fusion. BJU Int. 2011 Jan;107(1):53-7
11) Vourganti S, Rastinehad A, Yerram NK, Nix J, Volkin D, Hoang A, Turkbey B, Gupta GN, Kruecker J, Linehan WM, Choyke PL, Wood BJ, Pinto PA. Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsies. J Urol. 2012 Dec;188(6):2152-7