Stavrinides, Vasilis; (2021) Addressing the false positive MRI phenotype in prostate cancer diagnosis and management. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Multiparametric magnetic resonance imaging (mpMRI) is set to dominate the diagnosis and active surveillance of prostate cancer. However, false positive MRIs confound clinical decision-making and prompt unwarranted biopsies that carry morbidity risks. This is a significant issue: NICE currently recommends pre-biopsy MRI in men with suspected prostate cancer and, as 80,000 patients undergo biopsy every year in England and Wales, between 12,600 to 17,300 are expected to be biopsy-negative. Furthermore, MRI in active surveillance (AS) is strongly recommended by NICE for risk stratification at baseline and for the detection of oncological progression. However, MRI-based AS is new and it is still unknown when observed dynamic MRI changes reflect true transition to clinically significant disease. Recognising this on imaging is important for optimising clinical decisions and reducing the overall number of biopsies during AS. In this thesis it will be shown that MRI lesions seen in biopsy-naïve individuals with clinically significant cancer are larger, more conspicuous and more diffusion-restricted compared to phenotypes seen in men without significant disease. Furthermore, in men with indeterminate MRI phenotypes, PSA density and index lesion ADC predict the presence of significant cancer through a logistic regression model (mean cross-validated AUC: 0.77 [95% CI: 0.67–0.87]) and could help men avoid unnecessary biopsies. It is also shown that false positive MRI phenotypes in such men arise in prostatic regions with increased overall cellularity and expanded epithelium, while assuming either focal or diffuse patterns. In addition, it is demonstrated that MRI-based AS can be safely used to monitor men with insignificant disease, as approximately 84.7% (95% CI: 82.0–87.6) and 71.8% (95% CI: 68.2–75.6) of patients remain on AS at 3 and 5 years (with those with MRI-visible disease at baseline exiting earlier). Finally, it will be shown that progressing MRI lesions during imaging-based AS have two distinct histological phenotypes: one characterised by increased overall cellularity and expansion of epithelial areas (typically seen with transition to higher grade cancer) and another by moderate, standalone stromal hyperplasia seen in cases of pathological stability, not ideally requiring biopsy. This finding could lead to the development of radiological metrics that distinguish the two progression types and spare men from unnecessary biopsies in AS contexts.

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