Mathew, Manju Rachel; (2025) Histological assessment of Prostate cancer from an imaging perspective. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Prostate cancer is the second leading cause of cancer in men and the latest statistics estimate that 1 in 8 men will be diagnosed with it in their lifetime. The current diagnostic pathway involves the detection of disease by imaging modalities of multiparametric MRI (mpMRI) followed by confirmation of diagnosis by histopathological assessment, however despite the advances in this diagnostic pathway, 1 in 2 men who undergo a biopsy are found to not have significant disease; moreover, we do not know which men with prostate cancer actually need treatment (as most men will not die from their disease). Advanced MRI techniques have been developed specifically for the prostate to improve on the low specificity challenge faced when using mpMRI. However, these require careful validation. The Histo-MRI Mapping study is a prospective study aiming to clinically validate advanced MRI sequences in patients suspected of having prostate cancer. The sequences are validated against the histology of prostatectomy samples where radical prostatectomy is chosen as the treatment modality in biopsy-confirmed cases. In this thesis, the patients enrolled onto the study who then underwent prostatectomy were evaluated for the clinical and histological features in order to underpin imaging-histopathology correlations. The analysis demonstrated the rising trend of Gleason 3+4 disease in prostatectomy specimens compared to before the onset of MR targeted biopsy techniques, which likely reduces the prognostic significance of Gleason Grade groupings. Histological heterogeneity of the tumour foci in a cohort of the cases was examined at a scale similar to the base image resolution used in MR images, this has not previously been reported, and is a pre-requisite to detailed biological validation of imaging sequences. Imaging is an imperfect tool, the Histo-MRI Mapping study dataset allowed the histological assessment of MR- invisible lesions to understand the limitations of the MRI technique; it showed 27% of cases of prostatectomy specimens harbour such lesions, The main histological feature of a majority of these undetected lesions was their relatively small size which likely renders it impossible to be identified with current standard of care imaging. The findings of this thesis lays groundwork for the development and biological validation of novel imaging sequences.

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