Prostate cancer screening research can benefit from network medicine: an emerging awareness

Up to date, screening for prostate cancer (PCa) remains one of the most appealing but also a very controversial topics in the urological community. PCa is the second most common cancer in men worldwide and it is universally acknowledged as a complex disease, with a multi-factorial etiology. The pathway of PCa diagnosis has changed dramatically in the last few years, with the multiparametric magnetic resonance (mpMRI) playing a starring role with the introduction of the “MRI Pathway”. In this scenario the basic tenet of network medicine (NM) that sees the disease as perturbation of a network of interconnected molecules and pathways, seems to fit perfectly with the challenges that PCa early detection must face to advance towards a more reliable technique. Integration of tests on body fluids, tissue samples, grading/staging classification, physiological parameters, MR multiparametric imaging and molecular profiling technologies must be integrated in a broader vision of “disease” and its complexity with a focus on early signs. PCa screening research can greatly benefit from NM vision since it provides a sound interpretation of data and a common language, facilitating exchange of ideas between clinicians and data analysts for exploring new research pathways in a rational, highly reliable, and reproducible way

The value of MR textural analysis in prostate cancer

Current diagnosis and treatment stratification of patients with suspected prostate cancer relies on a combination of histological and magnetic resonance imaging (MRI) findings. The aim of this article is to provide a brief overview of prostate pathological grading as well as the relevant aspects of multiparametric (MRI) mpMRI, before indicating the potential that magnetic resonance textural analysis (MRTA) offers within prostate cancer. A review of the evidence base on MRTA in prostate cancer will enable discussion of the utility of this field while also indicating recommendations to future research. Radiomic textural analysis allows the assessment of spatial inter-relationships between pixels within an image by use of mathematical methods. First-order textural analysis is better understood and may have more clinical validity than higher-order textural features. Textural features extracted from apparent diffusion coefficient maps have shown the most potential for clinical utility in MRTA of prostate cancers. Future studies should aim to integrate machine learning techniques to better represent the role of MRTA in prostate cancer clinical practice. Nomenclature should be used to reduce misidentification between first-order and second-order energy and entropy. Automated methods of segmentation should be encouraged in order to reduce problems associated with inclusion of normal tissue within regions of interest. The retrospective and small-scale nature of most published studies, make it difficult to draw meaningful conclusions. Future larger prospective studies are required to validate the textural features indicated to have potential in characterisation and/or diagnosis of prostate cancer before translation into routine clinical practice

Multiparametric Tissue Characterization of Brain Neoplasms and Their Recurrence Using Pattern Classification of MR Images

Rationale and Objectives: Treatment of brain neoplasms can greatly benefit from better delineation of bulk neoplasm boundary and the extent and degree of more subtle neoplastic infiltration. MRI is the primary imaging modality for evaluation before and after therapy, typically combining conventional sequences with more advanced techniques like perfusion-weighted imaging and diffusion tensor imaging (DTI). The purpose of this study is to quantify the multi-parametric imaging profile of neoplasms by integrating structural MRI and DTI via statistical image analysis methods, in order to potentially capture complex and subtle tissue characteristics that are not obvious from any individual image or parameter. Materials and Methods: Five structural MR sequences, namely, B0, Diffusion Weighted Images, FLAIR, T1-weighted, and gadolinium-enhanced T1-weighted, and two scalar maps computed from DTI, i.e., fractional anisotropy and apparent diffusion coefficient, are used to create an intensity-based tissue profile. This is incorporated into a non-linear pattern classification technique to create a multi-parametric probabilistic tissue characterization, which is applied to data from 14 patients with newly diagnosed primary high grade neoplasms who have not received any therapy prior to imaging. Results: Preliminary results demonstrate that this multi-parametric tissue characterization helps to better differentiate between neoplasm, edema and healthy tissue, and to identify tissue that is likely progress to neoplasm in the future. This has been validated on expert assessed tissue. Conclusion: This approach has potential applications in treatment, aiding computer-assisted surgery by determining the spatial distributions of healthy and neoplastic tissue, as well as in identifying tissue that is relatively more prone to tumor recurrence

Improving The Diagnosis And Risk Stratification Of Prostate Cancer

The current diagnostic and stratification pathway for prostate cancer has led to over-diagnosis and over- treatment. This thesis aims to improve the prostate cancer diagnosis pathway by developing a minimally invasive blood test to inform diagnosis alongside mpMRI and to understand the true Gleason 4 burden which will help better stratify disease and guide clinicians in treatment planning. To reduce the number of patients who have to undergo prostate biopsy after indeterminate or false positive prostate mpMRI, we aimed to develop a new panel of mRNA detectable in blood or urine that was able to improve the detection of clinical significant prostate cancer (Gleason 4+3 or ≥6mm) in combination with prostate mpMRI. mRNA expression of 28 potential genes was studied in four prostate cancer cell lines and, using publicly available datasets, a new seven gene biomarker panel was developed using machine learning techniques. The signature was then validated in blood and urine samples from the ProMPT, PROMIS and INNOVATE trials. To redefine the classification of Gleason 4 disease in prostate cancer patients, digital pathology was used to contour and accurately assess the burden and spread of Gleason 4 in a cohort of PROMIS patients compared to the gold standard manual pathology. There was a significant difference between observed and objective Gleason 4 burden that has implications in patient risk stratification and biomarker discovery. The work presented in this thesis makes a significant step toward improving the patient diagnostic and risk classification pathways by ensuring only the right patients are biopsied when necessary, improving the current pathological reference standard

Virtual biopsy in abdominal pathology: where do we stand?

In recent years, researchers have explored new ways to obtain information from pathological tissues, also exploring non-invasive techniques, such as virtual biopsy (VB). VB can be defined as a test that provides promising outcomes compared to traditional biopsy by extracting quantitative information from radiological images not accessible through traditional visual inspection. Data are processed in such a way that they can be correlated with the patient’s phenotypic expression, or with molecular patterns and mutations, creating a bridge between traditional radiology, pathology, genomics, and artificial intelligence (AI). Radiomics is the backbone of VB, since it allows the extraction and selection of features from radiological images, feeding them into AI models in order to derive lesions' pathological characteristics and molecular status. Presently, the output of VB provides only a gross approximation of the findings of tissue biopsy. However, in the future, with the improvement of imaging resolution and processing techniques, VB could partially substitute the classical surgical or percutaneous biopsy, with the advantage of being non-invasive, comprehensive, accounting for lesion heterogeneity, and low cost. In this review, we investigate the concept of VB in abdominal pathology, focusing on its pipeline development and potential benefits

The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed