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There are many reasons why MRI-targeted biopsies (MRTB) in men with positive MRI scans fail to detect high-grade cancers that are found incidentally by concurrent systemic biopsies. Multiple factors often acting together contribute to the missed diagnoses of ISUP GG ≥ 2 cancers and/or tumour under grading [1]. The most obvious cause is an MRI invisible lesion on a background of transition zone hyperplasia, peripheral zone scarring/inflammation, or in difficult to evaluate regions such as adjacency to the ejaculatory ducts, central zone, bladder, low apex, or the anterior fibromuscular stroma. Some histologic subtypes of GG ≥ 2 prostate cancers are also difficult to see such as non-mass forming (microfocal) GG2 cancers and small cribriform tumours. Inevitably, radiologic perception errors also contribute, related to image quality, observer experience and variability, and misclassifications errors.
Even when an MRI is called positive, cancers may not be found because of false positive lesions [2]. MRTB errors also occur relating to the poorer visibility of MRI-detected lesions by ultrasound targeting methods, segmentation and misregistration errors, the experience of biopsy performing operators, and biopsy method, including the approach, number, and framing of targeting biopsy cores. Targeting errors seem most impactful for smaller and indistinct lesions and for lesions that are in less accessible locations according to the biopsy method deployed. Additionally, we have come to realise that hyper-precise targeting methods can lead to grade migrations, with a danger of over-diagnosis and overtreatment of some men [3]. For all of these reasons, many urologists recommend the use of systemic biopsies for all men at elevated risk of having high-grade prostate cancer, with additional MRTB in men with positive scan results. On the other hand, the European Association of Urology guideline recommends the combined biopsy approach only in men with positive MRI scans, with safety netting for men with negative MRI scans according to their individualised risk [4].
Recently, urological and radiologic thinking has changed after realising that systemic biopsies may not be needed when the chance of missing a large lesion is low, or when a systemic biopsy has already been done beforehand [4]. This theme is investigated by Deniffel et al [5] who showed that systemic biopsies are unnecessary in men with large MRI-identified lesions, additionally noting that systemic biopsies had little value in men with previous negative systemic biopsies. They showed that in men with PI-RADS category 5 lesions, a systematic biopsy could be avoided in 27% while missing GG ≥ 2 cancer in only 1%. In men with prior negative systemic biopsies, an additional systematic biopsy was avoidable in 58%, while missing GG ≥ 2 cancer in 2%. These findings are concordant with the analysis of Ahdoot et al who showed a greater added value for MRTB men with PI-RADS 4-5 lesions and a greater added value of systemic biopsies for men with lower PI-RADS category scores [6]. Their analysis of the TRIO study confirmed that improved GG ≥ 2 detection of combined biopsies was restricted to only men with smaller (PI-RADS 4) or indeterminate (PI-RADS 3) MRI lesions. Not undertaking systemic biopsies in men with PI-RADS 5 category lesions would lead to missing GG ≥ 2 cancers in 1.3% [6].
However, as radiologists, we also need to address the issue of whether systemic biopsies are the optimal solution for overcoming targeting errors. For smaller lesions, the PI-RADS committee proposed the use of focal saturation biopsies or regional target biopsies (RTB) [7]. A recent systemic analysis showed that RTB yields for detecting GG ≥ 2 cancers are not different to combined targeted and systematic biopsies, with the benefits of using fewer biopsy cores [8]. As in the studies of Deniffel and Adhoot, the MRI-directed RTB approach was superior to targeted biopsies alone for detecting GG ≥ 2 cancers (p < 0.001). A prospective randomized clinical study also shows non-inferiority of the MRI-directed RTB approach for high-grade cancer detection (Detection of clinically significant prostate cancer using target biopsy with 4 cores vs. target saturation biopsy with 9 cores in transperineal prostate fusion biopsy – a prospective randomized trial by Saner YM, Wiesenfarth M, Weru V, et al accepted by Euro Urol Oncol).
The optimal framing of the biopsy cores per MRI suspicious lesion has also become clearer. Raman et al reported that RTB had a GG ≥ 2 detection rate that was similar to combined systematic and targeted biopsy, with similar rates of upgrading on prostatectomy utilizing 4 fewer core biopsies per patient [9]. Brisbane et al noted that the number and distribution of cores depend on MRI characteristics including the suspicion category, the size, number, and locations of lesions [10]. Importantly, Brisbane et al noted that the majority of GG ≥ 2 cancers were found within, but also immediately around MRI-defined lesions. The width of the penumbra encompassing 90% of the cores with GG ≥ 2 lesions was radially < 5 mm for larger category 5 lesions, whereas it was radially < 12 mm for smaller category 4 lesions.
An additional advantage of RTB is that grade migration bias can be ameliorated when histologic adjustments are made when examining the biopsy cores [11]. An improved tumour volume estimation assessed against prostatectomy specimens is also noted compared to targeted biopsies [9]. The latter has implications for treatment planning including active surveillance, surgery, focal treatment, or (intraprostatic boosted) radiation.
Full assessments on the biopsy management and clinical and prognostic impacts of the RTB approach remain outstanding issues. Undoubtedly, the RTB approach increases core numbers while preserving the benefits of MRI-directed biopsies including fewer negative cores and fewer detected indolent cancers [7]. However, biopsy complication rates are related to the number of biopsy cores taken [12] which needs to be remembered. RTB is also not applicable when multiple lesions are present, for diffuse and heterogenous lesions [5, 6, 10], in men with diffuse PI-RADS 3 lesions. Men with anterior lesions in larger glands may also require additional cores. Thus, while we agree with the general premise of Deniffel et al on the need for a “..judicious use of additional systematic biopsy” [4], we feel that RTB will become the new standard to overcome targeting errors and that systematic biopsies will only be needed in men negative MRI scans when there is a high clinical suspicion due to higher PSA-density or when there is a strong family history for safety netting.
ReferencesWilliams C, Ahdoot M, Daneshvar MA et al (2022) Why does magnetic resonance imaging-targeted biopsy miss clinically significant cancer? J Urol 207:95–107. https://doi.org/10.1097/JU.0000000000002182
Stavrinides V, Syer T, Hu Y et al (2021) False positive multiparametric magnetic resonance imaging phenotypes in the biopsy-naïve prostate: are they distinct from significant cancer-associated lesions? Lessons from PROMIS. Eur Urol 79:20–29. https://doi.org/10.1016/j.eururo.2020.09.043
Vickers AJ (2021) Effects of magnetic resonance imaging targeting on overdiagnosis and overtreatment of prostate cancer. Eur Urol 80:567–572. https://doi.org/10.1016/j.eururo.2021.06.026
Mottet N, Cornford P, Van Den Bergh RCN (2022) EAU - EANM - ESTRO - ESUR - ISUP - SIOG guidelines on prostate cancer. EAU Guidel Edn Present EAU Annu Congr Amsterdam 2022 ISBN 978-94-92671-16-5
Deniffel D, Perlis N, Ghai S et al (2022) Prostate biopsy in the era of MRI-targeting: towards a judicious use of additional systematic biopsy. Eur Radiol. https://doi.org/10.1007/s00330-022-08822-3
Ahdoot M, Lebastchi AH, Long L et al (2021) Using Prostate Imaging-Reporting and Data System (PI-RADS) scores to select an optimal prostate biopsy method: a secondary analysis of the TRIO study. Eur Urol Oncol 24:1110–1119. https://doi.org/10.1016/j.euo.2021.03.004
Padhani AR, Barentsz J, Villeirs G et al (2019) PI-RADS Steering Committee: the PI-RADS multiparametric MRI and MRI-directed biopsy pathway. Radiology 292:464–474. https://doi.org/10.1148/radiol.2019182946
Hagens MJ, Fernandez Salamanca M, Padhani AR et al (2022) Diagnostic performance of a magnetic resonance imaging-directed targeted plus regional biopsy approach in prostate cancer diagnosis: a systematic review and meta-analysis. Eur Urol Open Sci 40:95–103. https://doi.org/10.1016/j.euros.2022.04.001
Raman AG, Sarma KV, Raman SS et al (2021) Optimizing spatial biopsy sampling for the detection of prostate cancer. J Urol 206:595–603. https://doi.org/10.1097/JU.0000000000001832
Brisbane WG, Priester AM, Ballon J et al (2022) Targeted prostate biopsy: umbra, penumbra, and value of perilesional sampling. Eur Urol 1–8. https://doi.org/10.1016/j.eururo.2022.01.008
Iczkowski KA, van Leenders GJLH, van der Kwast TH (2021) The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. Am J Surg Pathol 45:1007. https://doi.org/10.1097/PAS.0000000000001678
Simsir A, Kismali E, Mammadov R et al (2010) Is it possible to predict sepsis, the most serious complication in prostate biopsy? Urol Int 84:395–399. https://doi.org/10.1159/000296290
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Cite this articlePadhani, A.R., Raman, S.S. & Schoots, I.G. Towards a judicious use of perilesional biopsy in the era of MRI-targeting, parting of the ways from systematic prostate biopsy. Eur Radiol (2022). https://doi.org/10.1007/s00330-022-09097-4
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