Traditionally, diagnosis of PCa relied on extended transrectal US (TRUS)-guided systematic sampling of the prostate. This approach, however, frequently misses or underestimates the disease burden given the inability of ultrasound to distinguish between PCa and benign prostatic tissue. Recently, the quick adoption of targeted biopsies (TBx) has led to an increase in the detection rate of clinically significant PCa (csPCa) compared with TRUS-guided biopsy alone. Moreover, TBx has been shown to better predict RP final pathologic features compared with systematic biopsies. Different approaches are available for targeting lesions identified at prebiopsy multiparametric magnetic resonance imaging (MRI), including: (a) cognitive registration, which uses information on the location of the suspicious areas with the goal of sampling that region; (b) software-assisted fusion; and (c) direct, MRI-guided, in-bore biopsy. While some studies have suggested that MRI In-Bore biopsies are superior to MRI TRUS fusion biopsies in the detection of clinically significant PCa, it remains unknown whether the precision inherent to this spatially selective technique increases the likelihood of non-indolent PCa overestimation resulting in a downgrade to indolent PCa detection. Conversely, because systematic sampling is not performed during In-Bore biopsies, MRI-invisible lesions that may be detected with fusion plus systematic biopsies could be missed with the in-bore paradigm. Thus, while targeted biopsies improve the prediction of final radical prostatectomy pathologic features compared with systematic sampling alone, it is unknown whether different targeting techniques have different PCa vs. csPCa detection rates and moreover, no information is available regarding the overall percentage of malignant tissue sampled accoridng to the preferred techinique.
Currently, there is no consensus, nor evidence, on which type of MR-targeted biopsy performs better in terms of cancer detection rate. Instead, it has been demonstrated in several investigations that MR-directed biopsy performs better than TRUS-guided biopsy. Up to date, there are few studies that directly showed that no significant advantage of MRI In-bore compared with MRI-TRUS TBx exists for overall PCa detection, neither for csPCa detection. In 2017, Wegelin et al. [24] showed that no significant advantage of MRI In-bore compared with MRI-TRUS TBx exists for overall PCa detection (p=0.13), neither for csPCa detection, as it did not differ in our study. In 2019, in the FUTURE trial [25] 665 biopsy-naïve patients were recruited, and no significant differences in the detection rates of overall PCa among three patients groups (TURS-TBx 49.4%, SBx- TB 43.6%, and MRI In-Bore TBx 54.5%, p=0.40) was found. However, there were significant differences in the number of cores taken per technique with a median number of cores of 4 for FUS-TB (IQR 3-5), 3 for COG-TB (IQR 3-4), and 2 for MRI-TB (IQR 2-3; p
A critical point of innovation of the present research project is indeed represented by the aim to define differences among the two techniques regarding the percentages of positive cores sampled. Several investigations have indeed shown the paramount value of the amount of tumor in prostate needle cores, for correct patient management, in different settings: in the prediction of PSA failure among men undergoing radical prostatectomy [26, 27]; as part of nomograms to predict pathologic stage, extra-prostatic extension, seminal vesicle invasion, and radiation therapy failure [28-30]; as survival prognostic factor for patients treated with dose-escalated external beam radiotherapy; and as the best predictor of the probability of clinically insignificant PCa detection to enroll patients in active surveillance (AS) protocols. Schoots et al [31] in a systematic review and meta-analysis on the role of MR-directed biopsy in addition to systematic confirmatory biopsy in men on active surveillance for low-risk PCa, found that no pathway was more favorable than the other. However, the highest upgrading (Gleason >/= 3+4) was found in 27% (95%CI 22-34%) using a combined approach of MRI-targeted biopsies and confirmatory systematic biopsies. In addition, for AS patients, in two large cohorts, the number of cancer cores and the greatest percentage of cores involved at first biopsy were significant predictors of both PCa reclassification and increased tumor extent at re-biopsy [32-33]. Such data suggest that MRI In-bore biopsy, being able to achieve a higher percentage of tumor per biopsy core, might provide a critical clinical impact in the risk stratification and management of patients on AS, for both diagnosis and follow-up. For this reason, our research project will be aimed to provide new insights in this direction. One of the main objectives will be indeed to provide evidence to cover the current unmet need of Guidelines based on pathologic parameters from MRDB to stratify patients' risk and define proper therapeutic planning.
A second relevant innovation related to this project is represented by the biopsy operator being the same radiologist that reported the MR exam, with an increased probability that transposition errors might be significantly reduced. Additionally, the expertise of the performing operator is a further point of investigation. Recently, Park et al [29] published a systematic review and meta-analysis on PI-RADS v.2 inter-reader agreement. They found that the difference in reader experience was the single significant factor affecting study heterogeneity. These data underline how expertise-related factors might influence the performance of the MRI pathway, and why differently from other studies, in our research project the number of cores between the two techniques will tend to not numerically differ and will be determined by the same experienced operator on the basis of every single case enrolled.
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