Ahmed, HU; (2014) An evaluation of focal therapy in the treatment of localised prostate cancer. Doctoral thesis , UCL (University College London).

Abstract

In this doctoral thesis I am proposing a paradigm shift in the management of men with localised prostate cancer involving destroying areas of prostate cancer alone – so-called focal therapy. By doing so, I propose that side-effects of whole-gland therapies will be reduced whilst maintaining cancer control. I have carried out a phased and structured programme of work to test this hypothesis. First, I review the literature to define the current problem faced by men with localised prostate cancer – namely over-diagnosis and over-treatment with treatment-related side-effects. I demonstrate why multifocality of prostate cancer seems the key impediment to tissue preservation (focal therapy) and why our thinking on multifocality should change. Second, I then tackle how we can accurately localised disease. I evaluate and determine that that using template mapping biopsies is more accurate at localising clinically significant lesions compared to transrectal ultrasound-guided biopsies. Further, I show that histological features of poor prognosis predominantly reside with the index lesion in the presence of multifocal disease. I then evaluate the role of multi-parametric MRI in detecting and ruling-out clinically significant disease using two key and unique datasets of men. I show that the negative predictive value of multi-parametric MRI – the key attribute when proposing to leave parts of the prostate untreated - ranges from 90% to 95% for clinically significant cancer. Third, I evaluate the side-effects and early disease control outcomes of focal therapy within two prospective development studies which are research ethics committee and National Cancer Research Network approved. The Hemi-HIFU study demonstrated that approximately 90% of 20 men treated with hemiablation for unilateral cancer, achieved the trifecta status of pad-free, leak-free continence, erections sufficient for intercourse and cancer control at 12 months. The Focal-HIFU study demonstrated that focal therapy targeted individual lesions rather than one-half of a prostate leads to trifecta outcomes in 84% of 41 men. These results are extraordinary when one considers that trifecta rates after radical therapy are in the order of 50%. My data support the contention that focal therapy has a role in decreasing many of the harms associated with standard whole-gland therapies. This programme of work has now led to a number of multicentre trials testing the reproducibility of these findings with longer follow-up. It has also led to a change in standard practice across a number of international centres. Ultimately, comparative effectiveness research will be necessary to determine the true role of focal therapy in treating localised prostate cancer.

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