The impact of mpMRI-targeted vs systematic biopsy on the risk of prostate cancer downgrading at final pathology.

PURPOSE: Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. METHODS: We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4-5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2-5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). RESULTS: Overall, 12 vs 14 vs 6% (n = 176 vs 227 vs 96) downgrading rates were recorded in group 1 vs group 2 vs group 3, respectively (p < 0.001). At MVA, group 2 was more likely to be downgraded (OR 1.26, p = 0.04), as compared to group 1. Conversely, group 3 was less likely to be downgraded at RP (OR 0.42, p < 0.001). CONCLUSIONS: Downgrading rates are highest when PCa is present in TBx only and, especially when the highest grade PCa is diagnosed by TBx cores only. Conversely, downgrading rates are lowest when PCa is identified with the same ISUP through both SBx and TBx. The presence of clinically significant disease at SBx + TBx may indicate a more reliable assessment of the disease at the time of biopsy potentially reducing the risk of downgrading at final pathology.

WITHDRAWN: The benefit of adopting Microultrasound in the prostate cancer imaging pathway : A lesion-by-lesion analysis

INTRODUCTION: Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS≥3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern≥4 at histology. RESULTS: In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy.

The benefit of adopting Microultrasound in the prostate cancer imaging pathway: A lesion-by-lesion analysis: Biopsies prostatiques guidée par micro-échographie, quel bénéfice ? Une analyse lésion par lésion.

INTRODUCTION: - Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: - Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS ≥ 3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern ≥ 4 at histology. RESULTS: - In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16 ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: - Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy. © 2022 Elsevier Masson SAS. All rights reserved.

Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling.

Intersectin-long (ITSN-L) contains the invariant Dbl homology (DH) and pleckstrin homology (PH) domain structure characteristic of the majority of Dbl family proteins. This strict domain topography suggests that the PH domain serves an essential, conserved function in the regulation of the intrinsic guanine nucleotide exchange activity of the DH domain. We evaluated the role of the PH domain in regulating the DH domain function of ITSN-L. Surprisingly, we found that the PH domain was dispensable for guanine nucleotide exchange activity on Cdc42 in vitro, yet the PH domain enhanced the ability of the DH domain to activate Cdc42 signaling in vivo. PH domains can interact with phosphoinositide substrates and products of phosphatidylinositol 3-kinase (PI3K). However, PI3K activation did not modulate ITSN-L DH domain function in vivo.