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Simple Summary: In the realm of next-generation imaging, whole-body MRI (WB-MRI) is evolving as a key player in the modern management of patients with prostate cancer, showing great potential in the initial staging of high-risk disease, post-treatment evaluation, and recurrence assessment. This technique showcases both notable agreement and complementarity with PET/CT, particularly in identifying secondary bone, nodal, and visceral lesions. WB-MRI's strength lies in its "one size fits all" nature, avoiding contrast agents and radiotracers and adapting to diverse patient needs. Leveraging DWI and rFF%, it excels in bone metastasis detection, offering a comprehensive view. With promising potential for precise response assessment, WB-MRI emerges as a transformative tool in the management of metastatic prostate cancer. Prostate cancer ranks among the most prevalent tumours globally. While early detection reduces the likelihood of metastasis, managing advanced cases poses challenges in diagnosis and treatment. Current international guidelines support the concurrent use of 99Tc-Bone Scintigraphy and Contrast-Enhanced Chest and Abdomen CT for the staging of metastatic disease and response assessment. However, emerging evidence underscores the superiority of next-generation imaging techniques including PSMA-PET/CT and whole-body MRI (WB-MRI). This review explores the relevant scientific literature on the role of WB-MRI in metastatic prostate cancer. This multiparametric imaging technique, combining the high anatomical resolution of standard MRI sequences with functional sequences such as diffusion-weighted imaging (DWI) and bone marrow relative fat fraction (rFF%) has proved effective in comprehensive patient assessment, evaluating local disease, most of the nodal involvement, bone metastases and their complications, and detecting the increasing visceral metastases in prostate cancer. It does have the advantage of avoiding the injection of contrast medium/radionuclide administration, spares the patient the exposure to ionizing radiation, and lacks the confounder of FLARE described with nuclear medicine techniques. Up-to-date literature regarding the diagnostic capabilities of WB-MRI, though still limited compared to PSMA-PET/CT, strongly supports its widespread incorporation into standard clinical practice, alongside the latest nuclear medicine techniques. [ABSTRACT FROM AUTHOR]

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with wholemount specimens and PSMA-PET parameters. Methods: We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated. Results: Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen’s kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen’s kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively). Conclusions: We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiparametric Magnetic Resonance Imaging (mpMRI) interpretation and reporting is based on the more recent version 2.1 of the Prostate Imaging-Reporting and Data System (PI-RADS), revised in 2019, indicating the probability of clinically significant Prostate Cancer (csPCa) on a 5-point scale, which should be confirmed through trans-rectal ultrasound (TRUS) fusion-targeted biopsy. Among PI-RADS categories, PI-RADS 3 lesions represent a highly "equivocal" result, with a non-negligible probability of PCa, or even csPCa. This study exploits machine learning methods in order to investigate the role of mpMRI as a stand-alone tool for early and non-invasive detection of PCa in a selected cohort of PI-RADS 3 lesions, by means of a radiomic analysis of Apparent Diffusion Coefficient sequences. Differently from what reported in the current literature, the methodology adopted has bounded the possibility of overoptimistic predictive performance, also improving the state-of-art by achieving a positive predictive value of 80%, with specificity = 76% and sensitivity = 78%. The Prostate Imaging and Reporting Data System (PI-RADS) has a key role in the management of prostate cancer (PCa). However, the clinical interpretation of PI-RADS 3 score lesions may be challenging and misleading, thus postponing PCa diagnosis to biopsy outcome. Multiparametric magnetic resonance imaging (mpMRI) radiomic analysis may represent a stand-alone noninvasive tool for PCa diagnosis. Hence, this study aims at developing a mpMRI-based radiomic PCa diagnostic model in a cohort of PI-RADS 3 lesions. We enrolled 133 patients with 155 PI-RADS 3 lesions, 84 of which had PCa confirmation by fusion biopsy. Local radiomic features were generated from apparent diffusion coefficient maps, and the four most informative were selected using LASSO, the Wilcoxon rank-sum test (p < 0.001), and support vector machines (SVMs). The selected features where augmented and used to train an SVM classifier, externally validated on a holdout subset. Linear and second-order polynomial kernels were exploited, and their predictive performance compared through receiver operating characteristics (ROC)-related metrics. On the test set, the highest performance, equally for both kernels, was specificity = 76%, sensitivity = 78%, positive predictive value = 80%, and negative predictive value = 74%. Our findings substantially improve radiologist interpretation of PI-RADS 3 lesions and let us advance towards an image-driven PCa diagnosis. [ABSTRACT FROM AUTHOR]

Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus CalmetteGuerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible. [ABSTRACT FROM AUTHOR]

Lymphedema is a chronic progressive disorder that significantly compromises patients' quality of life. In Western countries, it often results from cancer treatment, as in the case of post-radical prostatectomy lymphedema, where it can affect up to 20% of patients, with a significant disease burden. Traditionally, diagnosis, assessment of severity, and management of disease have relied on clinical assessment. In this landscape, physical and conservative treatments, including bandages and lymphatic drainage have shown limited results. Recent advances in imaging technology are revolutionizing the approach to this disorder: magnetic resonance imaging has shown satisfactory results in differential diagnosis, quantitative classification of severity, and most appropriate treatment planning. Further innovations in microsurgical techniques, based on the use of indocyanine green to map lymphatic vessels during surgery, have improved the efficacy of secondary LE treatment and led to the development of new surgical approaches. Physiologic surgical interventions, including lymphovenous anastomosis (LVA) and vascularized lymph node transplant (VLNT), are going to face widespread diffusion. A combined approach to microsurgical treatment provides the best results: LVA is effective in promoting lymphatic drainage, bridging VLNT delayed lymphangiogenic and immunological effects in the lymphatic impairment site. Simultaneous VLNT and LVA are safe and effective for patients with both early and advanced stages of post-prostatectomy LE. A new perspective is now represented by the combination of microsurgical treatments with the positioning of nano fibrillar collagen scaffolds (BioBridgeTM) to favor restoring the lymphatic function, allowing for improved and sustained volume reduction. In this narrative review, we proposed an overview of new strategies for diagnosing and treating post-prostatectomy lymphedema to get the most appropriate and successful patient treatment with an overview of the main artificial intelligence applications in the prevention, diagnosis, and management of lymphedema. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to correlate primary staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) parameters with either prostate final histopathology (pT) or PSMA-immunochemistry (IHC) features in a cohort of high-risk prostate cancer (PCa) patients. Our study demonstrated a correlation between higher SUVmax and IHC-PSMA expression. Moreover, we found correlations between higher total lesion PSMA (PSMA-TL) values and the risk of lymphovascular invasion (LVI), and between PSMA tumor volume (PSMA-TV) and the presence of a cribriform pattern. Our results, if validated by further studies, may help to better identify unfavorable features showed by PSMA-PET/CT in primary staging, thus improving patients' management. PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44–50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Early diagnosing clinically significant prostate cancer (csPCa) through Magnetic Resonance Imaging (MRI) is very challenging and, nowadays, csPCa confirmation comes exclusively from prostate biopsy. However, biopsy is an invasive procedure and it also frequently causes csPCa misclassification. This study develops a non-invasive machine learning method for early predicting csPCa based on radiomic MRI image analysis. The main novelty of this study is investigating the radiomic differences between progressive risk groups of PCa, attributed according to the biopsy outcome and Gleason Grade group stratification. Besides predicting csPCa with very good performance (sensitivity = specificity = 84% in the test phase), this study highlights patients with GG = 2 as non-csPCa (being statistically equivalent to GG = 1), so that GG = 2 can be counselled for follow up, whilst GG ≥ 3 admitted to radical treatments. Not least, this study provides a plausible clinical interpretation of radiomic features, by discussing their values with respect to the histological meaning. The risk of misclassifying clinically significant prostate cancer (csPCa) by multiparametric magnetic resonance imaging is consistent, also using the updated PIRADS score and although different definitions of csPCa, patients with Gleason Grade group (GG) ≥ 3 have a significantly worse prognosis. This study aims to develop a machine learning model predicting csPCa (i.e., any GG ≥ 3 lesion at target biopsy) by mpMRI radiomic features and analyzing similarities between GG groups. One hundred and two patients with 117 PIRADS ≥ 3 lesions at mpMRI underwent target+systematic biopsy, providing histologic diagnosis of PCa, 61 GG < 3 and 56 GG ≥ 3. Features were generated locally from an apparent diffusion coefficient and selected, using the LASSO method and Wilcoxon rank-sum test (p < 0.001), to achieve only four features. After data augmentation, the features were exploited to train a support vector machine classifier, subsequently validated on a test set. To assess the results, Kruskal–Wallis and Wilcoxon rank-sum tests (p < 0.001) and receiver operating characteristic (ROC)-related metrics were used. GG1 and GG2 were equivalent (p = 0.26), whilst clear separations between either GG[1,2] and GG ≥ 3 exist (p < 10 − 6 ). On the test set, the area under the curve = 0.88 (95% CI, 0.68–0.94), with positive and negative predictive values being 84%. The features retain a histological interpretation. Our model hints at GG2 being much more similar to GG1 than GG ≥ 3. [ABSTRACT FROM AUTHOR]

Multiparametric MRI has been established as the most accurate non-invasive diagnostic imaging tool for detecting prostate cancer (PCa) in both the peripheral zone and the transition zone (TZ) using the PI-RADS (Prostate Imaging Reporting and Data System) v. 2.1 released in 2019 as a guideline to reporting. TZ PCa remains the most difficult to diagnose due to a markedly heterogeneous background and a wide variety of atypical imaging presentations as well as other anatomical and pathological processes mimicking PCa. The aim of this paper was to present a spectrum of PCa in the TZ, as a guide for radiologists. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) in the detection of local recurrence of prostate cancer (PCa) with the evaluation of the added value of signal Intensity/Time (I/T) curves. Materials and methods: A retrospective analysis of 22 patients undergoing mpMRI from 2015 to 2020 was carried out, with the following inclusion criteria: performing transrectal ultrasound guided biopsy within 3 months in the case of positive or doubtful findings and undergoing biopsy and/or clinical follow-up for 24 months in the case of negative results. The images were reviewed, and the lesions were catalogued according to morphological, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) features. Results: The presence of local recurrence was detected in 11/22 patients (50%). Greater diameter, hyperintensity on DWI, positive contrast enhancement and type 2/3 signal I/T curves were more frequently observed in patients with local recurrence (all p < 0.05). Of all the sequences, DCE was the most accurate; however, the combination of DCE and DWI showed the best results, with a sensitivity of 100%, a specificity of 82%, a negative predictive value of 100% and a positive predictive value of 85%. Conclusions: The utility of MRI in the detection of local recurrence is tied to the multiparametric approach, with all sequences providing useful information. A combination of DCE and DWI is particularly effective. Moreover, specificity could be additionally improved using analysis of the signal I/T curves. [ABSTRACT FROM AUTHOR]

Purpose: The conventional imaging flowchart for prostate cancer (PCa) staging may fail in correctly detecting lymph node metastases (LNM). Pelvic lymph node dissection (PLND) represents the only reliable method, although invasive. A new amino acid PET compound, [18F]-fluciclovine, was recently authorized in suspected PCa recurrence but not yet included in the standard staging work-up of primary PCa. A prospective monocentric study was designed to evaluate [18F]-fluciclovine PET/CT diagnostic performance for preoperative LN staging in primary high-risk PCa. Methods: Consecutive patients (pts) with biopsy-proven PCa, standard staging (including [11C]choline PET/CT), eligible for PLND, were enrolled to undergo an investigational [18F]-fluciclovine PET/CT. Nodal uptake higher than surrounding background was reported by at least two readers (blinded to [11C]choline) using a visual 5-point scale (1–2 probably negative; 4–5 probably positive; 3 equivocal); SUVmax, target-to-background (aorta—A; bone marrow—BM) ratios (TBRs), were also calculated. PET results were validated with PLND. [18F]-fluciclovine PET/CT performance using visual score and semi-quantitative indexes was analyzed both per patient and per LN anatomical region, compared to conventional [11C]choline and clinical predictive factors (to note that diagnostic performance of [18F]-fluciclovine was explored for LNM but not examined for intrapelvic or extrapelvic M1 lesions). Results: Overall, 94 pts underwent [18F]-fluciclovine PET/CT; 72/94 (77%) high-risk pts were included in the final analyses (22 pts excluded: 8 limited PLND; 3 intermediate-risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant hormonal therapy). Median LNM risk by Briganti nomogram was 19%. LNM confirmed on histology was 25% (18/72 pts). Overall, 1671 LN were retrieved; 45/1671 (3%) LNM detected. Per pt, median no. of removed LN was 22 (mean 23 ± 10; range 8–51), of LNM was 2 (mean 3 ± 2; range 1–10). Median LNM size was 5 mm (mean 5 ± 2.5; range 2–10). On patient-based analyses (n = 72), diagnostic performance for LNM resulted significant with [18F]-fluciclovine (AUC 0.66, p 0.04; 50% sensitivity, 81% specificity, 47% PPV, 83% NPV, 74% accuracy), but not with [11C]choline (AUC 0.60, p 0.2; 50%, 70%, 36%, 81%, and 65% respectively). Briganti nomogram (OR = 1.03, p = 0.04) and [18F]-fluciclovine visual score (≥ 4) (OR = 4.27, p = 0.02) resulted independent predictors of LNM at multivariable analyses. On region-based semi-quantitative analyses (n = 576), PET/CT performed better using TBR parameters (TBR-A similar to TBR-BM; TBR-A fluciclovine AUC 0.61, p 0.35, vs choline AUC 0.57 p 0.54; TBR-BM fluciclovine AUC 0.61, p 0.36, vs choline AUC 0.58, p 0.52) rather than using absolute LN SUVmax (fluciclovine AUC 0.51, p 0.91, vs choline AUC 0.51, p 0.94). However, in all cases, diagnostic performance was not statistically significant for LNM detection, although slightly in favor of the experimental tracer [18F]-fluciclovine for each parameter. On the contrary, visual interpretation significantly outperformed PET semi-quantitative parameters (choline and fluciclovine: AUC 0.65 and 0.64 respectively; p 0.03) and represents an independent predictive factor of LNM with both tracers, in particular [18F]-fluciclovine (OR = 8.70, p 0.002, vs OR = 3.98, p = 0.03). Conclusion: In high-risk primary PCa, [18F]-fluciclovine demonstrates some advantages compared with [11C]choline but sensitivity for metastatic LN detection is still inadequate compared to PLND. Visual (combined morphological and functional), compared to semi-quantitative assessment, is promising but relies mainly on readers' experience rather than on unquestionable LN avidity. Trial registration: EudraCT number: 2014–003,165-15 [ABSTRACT FROM AUTHOR]

Multiparametric magnetic resonance imaging (mpMRI) can guide the surgical plan during robot-assisted radical prostatectomy (RARP), and intraoperative frozen section (IFS) can facilitate real-time surgical margin assessment. To assess a novel technique of IFS targeted to the index lesion by using augmented reality three-dimensional (AR-3D) models in patients scheduled for nerve-sparing RARP (NS-RARP). Between March 2019 and July 2019, 20 consecutive prostate cancer patients underwent NS-RARP with IFS directed to the index lesion with the help of AR-3D models (study group). Control group consists of 20 patients matched with 1:1 propensity score for age, clinical stage, Prostate Imaging Reporting and Data System score v2, International Society of Urological Pathology grade, prostate volume, NS approach, and prostate-specific antigen in which RARP was performed by cognitive assessment of mpMRI. In the study group, an AR-3D model was superimposed to the surgical field to guide the surgical dissection. Tissue sampling for IFS was taken in the area in which the index lesion was projected by AR-3D guidance. Chi-square test, Student t test, and Mann-Whitney U test were used to compare, respectively, proportions, means, and medians between the two groups. Patients in the AR-3D group had comparable preoperative characteristics and those undergoing the NS approach were referred to as the control group (all p ≥ 0.06). Overall, positive surgical margin (PSM) rates were comparable between the two groups; PSMs at the level of the index lesion were significantly lower in patients referred to AR-3D guided IFS to the index lesion (5%) than those in the control group (20%; p = 0.01). The novel technique of AR-3D guidance for IFS analysis may allow for reducing PSMs at the level of the index lesion. Augmented reality three-dimensional guidance for intraoperative frozen section analysis during robot-assisted radical prostatectomy facilitates the real-time assessment of surgical margins and may reduce positive surgical margins at the index lesion. We proposed a novel technique of augmented reality three-dimensional (AR-3D) guided intraoperative frozen section (IFS) for real-time assessment of surgical margins during robot-assisted radical prostatectomy. The AR-3D guidance for IFS allows combination of the reduction of positive surgical margins at the level of the index lesion and preservation of neurovascular bundles. [ABSTRACT FROM AUTHOR]

Introduction and Objective: ExactVuTM is a real-time micro-ultrasound system which provides, according to the Prostate Risk Identification Using Micro- Ultrasound protocol (PRI-MUS), a 300% higher resolution compared to conventional transrectal ultrasound. To evaluate the performance of ExactVuTM in the detection of Clinically significant Prostate Cancer (CsPCa). Materials and methods: Patients with Prostate Cancer diagnosed at fusion biopsy were imaged with ExactVuTM. CsPCa was defined as any Gleason Score ≥ 3+4. ExactVuTM examination was considered as positive when PRI-MUS score was ≥ 3. PRI-MUS scoring system was considered as correct when the fusion biopsy was positive for CsPCa. A transrectal fusion biopsy- proven CsPCa was considered as a gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operator characteristic (ROC) curve (AUC) were calculated. Results: 57 patients out of 68 (84%) had a csPCa. PRI-MUS score was correctly assessed in 68% of cases. Regarding the detection of CsPCa, ExactVuTM ’s sensitivity, specificity, PPV, and NPV was 68%, 73%, 93%, and 31%, respectively and the AUC was 0.7 (95% CI 0.5-0-8). For detecting CsPCa in the transition/ anterior zone the sensitivity, specificity, PPV, and NPV was 45%, 66%, 83% and 25% respectively ant the AUC was 0.5 (95% CI 0.2-0.9). Accounting only the CsPCa located in the peripheral zone, sensitivity, specificity, PPV, and NPV raised up to 74%, 75%, 94%, 33%, respectively with AUC 0.75 (95% CI 0.5-0-9). Conclusions: ExactVuTM provides high resolution of the prostatic peripheral zone and could represent a step forward in the detection of CsPCa as a triage tool. Further studies are needed to confirm these promising results. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. Materials and methods: Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram's derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. Results: 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. Conclusions: This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical impact of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography on the planned management of prostate cancer patients with biochemical recurrence after surgery. Methods: We enrolled 276 prostate cancer patients referred to 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography due to biochemical recurrence after surgery (two consecutive prostate‐specific antigen assays ≥0.2 ng/mL). First, the detection rate of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography was assessed according to different prostate‐specific antigen levels. Second, the independent predictors of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography positive results were assessed. Finally, the intended treatment before revision of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography was assessed by a multidisciplinary team based on the European Association of Urology guidelines, patient clinical condition and clinical parameters. Then, re‐assessment of the treatment plan was prospectively recorded by the same board after revision of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography. The effective clinical impact of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. Results: The overall detection rate of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography was 47.5%. Prostate‐specific antigen at 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography (odds ratio 3.52) and prostate‐specific antigen doubling time <3 months (odds ratio 3.98) were independent predictors of positive 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography results (all P ≤ 0.03). 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography led to a major treatment change in 177 cases (64.1%), with a minor clinical impact of 2.5%. The overall clinical impact of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography was 42.4%, 27.7%, 21.2% and 8.7% in men with prostate‐specific antigen at 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography of 0.2–0.4, 0.5–1, 1.1–2 and >2 ng/mL, respectively. Conclusions: 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography allows clinicians to radically change the intended treatment approach before imaging evaluation, in roughly two out three individuals. [ABSTRACT FROM AUTHOR]

We aimed to review the current state‐of‐the‐art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and positron‐emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta‐analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross‐sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high‐risk patients, but is still suggested by current clinical guidelines. Positron‐emission tomography/computed tomography with newer tracers has some advantage over conventional images, but is not cost‐effective. Bone scan and computed tomography are often useless in early biochemical relapse, when salvage treatments are potentially curative. New imaging modalities, such as prostate‐specific membrane antigen positron‐emission tomography/computed tomography and whole‐body magnetic resonance imaging, are showing promising results for early local and systemic detection. Newer imaging techniques, such as multiparametric magnetic resonance imaging, whole‐body magnetic resonance imaging and positron‐emission tomography/computed tomography with prostate‐specific membrane antigen, have the potential to fill the historical limitations of conventional imaging methods in some clinical situations of primary and secondary staging of prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer‐specific mortality‐free survival after surgery in pN1 prostate cancer patients through an external validation. Methods: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram‐derived probability cut‐off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. Results: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1–73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer‐specific mortality‐free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. Conclusions: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of multiparametric magnetic0 resonance imaging (mpMRI) to guide the nerve-sparing (NS) surgical plan in prostate cancer (PCa) patients referred to robot-assisted radical prostatectomy (RARP). Methods: One hundred thirty-seven consecutive PCa patients were submitted to RARP between September 2016 and February 2017 at two high-volume European centers. Before RARP, each patient was referred to 1.5T or 3T mpMRI. NS was recorded as Grade 1, Grade 2, Grade 3, and Grade 4 according to Tewari and colleagues classification. A preliminary surgical plan to determinate the extent of NS approach was recorded based on clinical data. The final surgical plan was reassessed after mpMRI revision. The appropriateness of surgical plan change was considered based on the presence of extracapsular extension or positive surgical margins (PSMs) at level of neurovascular bundles area at final pathology. Furthermore, we analyzed a control group during the same period of 166 PCa patients referred to RARP in both institutions without preoperative mpMRI to assess the impact of the use of mpMRI on the surgical margins. Results: Considering 137 patients with preoperative mpMRI, the mpMRI revision induced the main surgeon to change the NS surgical plan in 46.7% of cases on patient-based and 56.2% on side-based analysis. The surgical plan change results equally assigned between the direction of more radical and less radical approach both on patient-based (54.7% vs 54.3%) and on side-based levels (50% vs 50%), resulting an overall appropriateness of 75%. Moreover, patients staged with mpMRI revealed significant lower overall PSMs compared with control group with no mpMRI (12.4% vs 24.1%; p ≤ 0.01). Conclusions: mpMRI induces robotic surgeons to change the surgical plan in almost half of individuals, thus tailoring the NS approach, without compromising the oncologic outcomes. Compared to patients treated without mpMRI, the use of preoperative mpMRI can significantly reduce the overall PSMs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to review the current literature concerning the indication of pelvic lymph node dissection (PLND), its extent and complications in prostate cancer (PCa) staging, the available tools, and the future perspectives to assess the risk of lymph node invasion (LNI). Methods: A literature review was performed using the Medline, Embase, and Web of Science databases. The search strategy included the terms pelvic lymph nodes, PLND, radical prostatectomy, prostate cancer, lymph node invasion, biochemical recurrence, staging, sentinel lymph node dissection, imaging, and molecular markers. Results: PLND currently represents the gold standard for nodal staging in PCa patients. Available imaging techniques are characterized by poor accuracy in the prediction of LNI before surgery. On the contrary, an extended PLND (ePLND) would result into proper staging in the majority of the cases. Several models based on preoperative disease characteristics are available to assess the risk of LNI. Although ePLND is not associated with a substantial risk of severe complications, up to 10% of the men undergoing this procedure experience lymphoceles. Concerns over potential morbidity of ePLND led many authors to investigate the role of sentinel lymph node dissection in order to prevent unnecessary ePLND. Finally, the incorporation of novel biomarkers in currently available tools would improve our ability to identify men who should receive an ePLND. Conclusions: Nowadays, the most informative tools predicting LNI in PCa patients consist in preoperative clinical nomograms. Sentinel lymph node dissection still remains experimental and novel biomarkers are needed to identify patients at a higher risk of LNI. [ABSTRACT FROM AUTHOR]

Objectives To investigate cancer-specific mortality and other-cause mortality in prostate cancer patients with nodal metastases. Methods The study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan-Meier analyses were used to assess cancer-specific mortality-free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni- and multivariable competing risk Cox regression analyses were used to assess cancer-specific mortality and other-cause mortality. Finally, cumulative-incidence plots were generated for cancer-specific mortality and other-cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method. Results Men with prostate-specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer-specific mortality-free survival estimates as compared with their counterparts with prostate-specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate-specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8-10 were all independent predictors of cancer-specific mortality (all P-values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8-year cancer-specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively. Conclusions Three positive lymph nodes represent the best prognostic cut-off in node-positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients. [ABSTRACT FROM AUTHOR]

Background A complete biochemical response (BR) immediately after surgery could be considered an indicator of optimal cancer control after radical prostatectomy (RP). Objective To evaluate the prognostic value of early postoperative prostate-specific antigen (PSA) levels after RP in patients with lymph node invasion (LNI). Design, setting, and participants The study included 319 prostate cancer patients with LNI who were treated with RP and extended pelvic lymph node dissection (ePLND) at a single institution between 1998 and 2013. All men had complete clinical, pathologic, and follow-up data, including PSA value at 6 wk after surgery. Patients were divided into two groups according to PSA value at 6 wk after surgery: complete BR (PSA <0.1 ng/ml) and PSA persistence (PSA ≥0.1 ng/ml). Outcome measurements and statistical analysis Kaplan-Meier analyses were used to assess 8-yr clinical recurrence (CR) and cancer-specific mortality (CSM) rates according to PSA persistence after RP. Multivariable Cox regression analysis was used to test the association between PSA persistence and CR. Covariates consisted of pathologic Gleason score (≤7 vs ≥8), number of positive nodes, surgical margins status (negative vs positive), and adjuvant therapies (none vs androgen deprivation therapy (ADT) vs adjuvant radiotherapy plus ADT). When we performed multivariable analyses assessing the association between PSA persistence and CSM pathologic Gleason score represented the only covariate due to the low number of events ( n = 13). Results and limitations Overall, 83 patients (26%) had PSA persistence. Men with PSA persistence had higher 8-yr CR and CSM rates than those with complete BR (69% vs 12% and 16% vs 4.2%, respectively; all p ≤ 0.002). This was confirmed in multivariable analyses, where PSA persistence at 6 wk after surgery was an independent predictor of both CR (hazard ratio [HR]: 8.3; 95% confidence interval [CI], 4.73–14.7; p ≤ 0.001) and CSM (HR: 2.16; 95% CI, 1.63–2.86; p ≤ 0.001). Pathologic stage lower than pT3a, biopsy and pathologic Gleason score ≥8, positive surgical margins, and three or more positive lymph nodes were significantly associated with PSA persistence (all p ≤ 0.04). Our study is limited by its retrospective design. Conclusions Early BR can be achieved in approximately 75% of men with LNI submitted to RP and ePLND. PSA assessment early after surgery has an important prognostic role in the prediction of CR and CSM in node-positive patients. A risk stratification of these patients based on PSA persistence could guide physicians to properly select patients who may benefit the most from timely multimodal treatments. Patient summary The risk of clinical recurrence and cancer-specific mortality is heterogeneous in patients with prostate cancer with lymph node invasion. Node-positive patients with complete biochemical response early after surgery share more favorable oncologic outcomes than those with PSA persistence. These results are important to plan the optimal postoperative patient management. [ABSTRACT FROM AUTHOR]

We present the first case of salvage retroperitoneal lymph node dissection based on the results of 18F-FACBC PET/CT performed for a prostate-specific antigen relapse after radical prostatectomy. The patients underwent 11C-choline PET/CT, which turned out negative, while 18F-FACBC PET/CT visualized two lymph node metastases confirmed at pathological examination. Preliminary clinical reports showed an improvement in the detection rate of 20-40% for 18F-FACBC in comparison with 11C-choline, rendering the 18F-FACBC the potential radiotracer of the future. Salvage surgery for prostate cancer is a fascinating but controversial approach. New diagnostic tools may improve its potential by increasing the assessment and the selection of the patients. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate Cancer is one of the main threats to men's health. Its accurate diagnosis is crucial to properly treat patients depending on the cancer's level of aggressiveness. Tumor risk-stratification is still a challenging task due to the difficulties met during the reading of multi-parametric Magnetic Resonance Images. Artificial Intelligence models may help radiologists in staging the aggressiveness of the equivocal lesions, reducing inter-observer variability and evaluation time. However, these algorithms need many high-quality images to work efficiently, bringing up overfitting and lack of standardization and reproducibility as emerging issues to be addressed. This study attempts to illustrate the state of the art of current research of Artificial Intelligence methods to stratify prostate cancer for its clinical significance suggesting how widespread use of public databases could be a possible solution to these issues. Many efforts have been carried out for the standardization of multiparametric Magnetic Resonance (mp-MR) images evaluation to detect Prostate Cancer (PCa), and specifically to differentiate levels of aggressiveness, a crucial aspect for clinical decision-making. Prostate Imaging—Reporting and Data System (PI-RADS) has contributed noteworthily to this aim. Nevertheless, as pointed out by the European Association of Urology (EAU 2020), the PI-RADS still has limitations mainly due to the moderate inter-reader reproducibility of mp-MRI. In recent years, many aspects in the diagnosis of cancer have taken advantage of the use of Artificial Intelligence (AI) such as detection, segmentation of organs and/or lesions, and characterization. Here a focus on AI as a potentially important tool for the aim of standardization and reproducibility in the characterization of PCa by mp-MRI is reported. AI includes methods such as Machine Learning and Deep learning techniques that have shown to be successful in classifying mp-MR images, with similar performances obtained by radiologists. Nevertheless, they perform differently depending on the acquisition system and protocol used. Besides, these methods need a large number of samples that cover most of the variability of the lesion aspect and zone to avoid overfitting. The use of publicly available datasets could improve AI performance to achieve a higher level of generalizability, exploiting large numbers of cases and a big range of variability in the images. Here we explore the promise and the advantages, as well as emphasizing the pitfall and the warnings, outlined in some recent studies that attempted to classify clinically significant PCa and indolent lesions using AI methods. Specifically, we focus on the overfitting issue due to the scarcity of data and the lack of standardization and reproducibility in every step of the mp-MR image acquisition and the classifier implementation. In the end, we point out that a solution can be found in the use of publicly available datasets, whose usage has already been promoted by some important initiatives. Our future perspective is that AI models may become reliable tools for clinicians in PCa diagnosis, reducing inter-observer variability and evaluation time. [ABSTRACT FROM AUTHOR]

Background: We aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and Methods: Between 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.Results: A total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).Conclusions: The early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy. [ABSTRACT FROM AUTHOR]