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An evaluation of focal therapy in the treatment of localised prostate cancer

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.
Date January 2014
CreatorsAhmed, H. U.
PublisherUniversity College London (University of London)
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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