Association of Patient and Imaging-Related Factors with False Negative MRI-Targeted Prostate Biopsies of Suspicious PI-RADS 4 and 5 Lesions - Beyond the Abstract

The debate on the role of MRI-guided fusion biopsies (TBx) as an adjunct or replacement for the systematic biopsy (SBx) has persisted since the earliest days of TBx. Currently, the EAU recommends a combined approach.1 A consensus statement from the collaborative initiative between the American Urologic Association (AUA) and the Society of Abdominal Radiology advises a case-specific decision be made in order to maximize detection of clinically significant prostate cancer (csPCa).2 Despite advances in fusion biopsy technique and performance, it is not uncommon for a TBx of a lesion seen as suspicious on MRI to come back negative for csPCa. There are two possible explanations for this: 1) the MRI was falsely positive or, 2) the TBx itself was falsely negative and the lesion was missed. Therefore, a negative targeted biopsy of a highly suspicious lesion on mpMRI must be interpreted with caution and followed closely.

Most recently, Patel et al3 demonstrated a 10% absolute improved detection rate of csPCa (≥GG2) in men with PI-RADS 3 to 5 mpMRI lesions, when targeted biopsies were added to standard systematic biopsy. Additionally, Kim et al4 assessed the value of adding targeted transperineal sampling to systematic template sampling and demonstrated that template biopsy alone captured csPCa in 39% of men, targeted biopsy alone revealed csPCa in 38% of men, and the combined approach resulted in csPCa in 49% of their cohort. Resolving the question of whether a SBx can be omitted in select patients or whether a combined approach should always be done relies on identifying factors associated with missing clinically significant cancer on targeted biopsy in general.

In this present study, we aimed to identify the factors most likely to be associated with obtaining a false negative (FN) TBx, specifically of non-equivocal, suspicious (PI-RADS 4 and 5) lesions where csPCa was then detected on a subsequent systematic biopsy in the region of the MRI lesion. Our goal was to identify those patients at highest risk of a FN TBx who would most benefit from a combined SBx and TBx approach.

We looked at patient-specific and imaging-related factors that we believed may influence this: age, use of an enema prep before MRI, lesion size, absolute and percent difference in segmented prostate volume between US and MRI (a potential cause for fusion misregistration), presence of a suspicious DRE, biopsy indication (i.e. biopsy naïve, previous negative biopsy, or active surveillance), number of fusion cores taken, PSA density and urologist performing the biopsy. Using univariable and multivariable logistic regression modeling, we set out to determine what factors were associated with an increased probability of a FN TBx.

Our retrospective study included 361 PI-RADS 4/5 lesions in 304 patients that underwent combined SBx and TBx. A total of 67 (19%) TBx biopsied lesions were FN and captured on subsequent SBx. The remaining 294 (81%) TBx lesions were TP. The majority of men with FN biopsies had lower PSAD (85% of men <0.2 ng/ml2) compared to those men with TP biopsied lesions (84% of men with ≥0.2 ng/ml2, p-value: <0.0001). Further subgroup analysis of lesion size demonstrated that 98.9% of lesions defined as TP were >10mm, compared to 44.8% of lesions that resulted in FN biopsy (p<0.0001). Our model found a significant inverse association between lesion size (OR: 0.94, 95% CI 0.89 – 0.98), presence of a suspicious DRE (OR: 0.36,95% CI 0.15 – 0.85) and PSA density (OR: 0.01, 95% CI 0.001 – 0.234) on the probability of obtaining a FN TBx.

Our study further supports that combined systematic and targeted biopsies in men with PI-RADS 4/5 lesions on MRI improves detection of ≥GG2 cancer. Importantly, omitting systematic biopsies would have resulted in 19% of clinically significant prostate cancers missed. Thus, targeting lesions in men with lower PSAD and smaller suspicious mpMRI lesions (PI-RADS 4/5) appears to improve the yield of the biopsy session.

Written by: M. Movassaghi, F. Ahmed, H. Patel, L. Luk, E. Hyams, S. Wenske, H. Shaish

Department of Urology, Columbia University Irving Medical Center, New York, NY., Department of Radiology, Columbia University Irving Medical Center, New York, NY., Department of Surgery, Division of Urology, Brown University., Department of Urology, Columbia University Irving Medical Center, New York, NY.


  1. Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-62.
  2. Rosenkrantz AB, Verma S, Choyke P, Eberhardt SC, Eggener SE, Gaitonde K, et al. Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus Statement by AUA and SAR. J Urol. 2016;196(6):1613-8.
  3. Patel HD, Koehne EL, Shea SM, et al. Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions. J Urol. 2022 ;207(1):108-117.
  4. Kim MM, Wu S, Lin SX, et al. Transperineal Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy Combined with Standard Template Improves Prostate Cancer Detection. J Urol. 2022;207(1):86-94.

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