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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 99 Tc-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.

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.

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.

Background: We investigated the diagnostic accuracy of the new Prostate Imaging for Recurrence Reporting (PI-RR) score and its inter-observer variability. Secondly, we compared the detection rate of PI-RR and PET and analyzed the correlation between Prostate Specific Antigen (PSA) levels and the PI-RR score. Methods: We included in the analysis 134 patients submitted to multiparametric magnetic resonance imaging for suspected local recurrence. The images were independently reviewed by two radiologists, assigning a value from 1 to 5 to the PI-RR score. Inter-observer agreement and diagnostic accuracy of the PI-RR score (compared to histopathological data, available for 19 patients) were calculated. The detection rate was compared to those of choline PET/CT (46 patients) and PSMA PET/CT (22 patients). The distribution of the PSA values in relation to the PI-RR scores was also analyzed. Results: The accuracy of the PI-RR score was 68.4%. The reporting agreement was excellent (K = 0.884, p < 0.001). The PI-RR showed a higher detection rate than choline PET/CT (69.6% versus 19.6%) and PSMA PET-CT (59.1% versus 22.7%). The analysis of the PSA distribution documented an increase in the PI-RR score as the PSA value increased. Conclusion: The excellent reproducibility of the PI-RR score supports its wide use in the clinical practice to standardize recurrence reporting. The detection rate of PI-RR was superior to that of PET, but was linked to the PSA level.

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.

We identified two unstable variants in the third exon of α-globin genes: Hb Bernalda/Groene Hart (HBA1:c.358C>T), and Hb Caserta (HBA2:c.79G>A) in cis to Hb Sun Prairie (HBA2:c.391G>C), also named Hb Southern Italy. These mutations occurred in the H helix of the α-globin that is involved in heme contacting, specific recognition of α-hemoglobin-stabilizing protein (AHSP), and α 1 β 1 interactions. The carriers showed α-thalassemia phenotype, but one also jaundice and cholelithiasis. Molecular identification of clusters of families in Southern Italy encouraged molecular characterization of mRNA, globin chain analyses, molecular modeling studies, and comparison with globin variants to understand the mechanisms causing the α-thalassemia phenotype. A normal amount of Hb Bernalda/Groene Hart mRNA were found, and molecular modeling highlighted additional H bonds with AHSP. For Hb Southern Italy, showing an unexpected α/β biosynthetic ratio typical of the β-thalassemia type, two different molecular mechanisms were shown: Reduction of the variant mRNA, likely due to the No-Go Decay for the presence of unused triplet ACG at cod 26, and protein instability due to the impairment of AHSP interaction. The UDP glucuronosyltransferase 1A (UGT1A1) genotyping was conclusive in the case of jaundice and cholelithiasis. Multiple approaches are needed to properly identify the mechanisms leading to unstable variants and the effect of a mutation.