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INTRODUCTION

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The clinical management of prostate cancer has become increasingly complex, owing to a growing armamentarium of treatments from different medical specialties becoming available. In spite of prostate-specific antigen (PSA) testing, the presentation of prostate cancer at a locally advanced stage remains common in the UK, accounting for one-third of all new cases. The term ‘locally advanced prostate cancer’, however, is loosely used to encompass a spectrum of disease profiles that may include any of the following:

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  1. clinical stage T3 or T4, N0 or N1, and M0, at diagnosis;

  2. clinical stages T1 and T2 at diagnosis, where so-called ‘high-risk’ features indicate the likelihood of extraprostatic invasion or clinically undetectable metastatic disease;

  3. clinically localised tumour giving rise to recurrent or persistent local disease, or metastatic disease, following definitive treatment with radical prostatectomy or radical radiotherapy;

  4. pathological stage pT2 or pT3 disease with ‘high-risk’ features, where radiotherapy may be offered as adjuvant therapy following radical prostatectomy.

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There is little consensus on a definition for locally advanced prostate cancer, and it is therefore unsurprising that there is tremendous variation in therapeutic practice. Patients may be offered radical radiotherapy, radical prostatectomy or androgen deprivation therapy – either alone or in combination. For other patients, a period of watchful waiting, enrolment in a clinical trial or intervention with a novel or experimental therapeutic modality may be acceptable. The optimal combination, timing and intensity of treatment continue to be strongly debated, and clinical outcomes may vary substantially between patients with apparently similar tumour characteristics. Recognizing such evident limitations of a traditional concept of ‘locally advanced’ disease based upon tumour stage, newer concepts of disease risk are beginning to evolve based upon growing experience of clinical outcomes following alternative treatments, and refinements in diagnosis, pathological assessment and clinical staging.

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This chapter will consider the treatment of so-called ‘high-risk’ prostate cancer and concepts of risk categorization. During the past 20 years, the diagnosis and treatment of prostate cancer has become increasingly proactive. Concern has arisen that for many men with early-stage disease, the adverse effects of early treatment may outweigh the disease-specific risk. But, in spite of the potential advantages of this aggressive approach, the continuing high mortality from prostate cancer focuses interest in therapeutic strategies that may improve survival for men with locally advanced disease, and in diagnostic strategies that may identify patients for whom this benefit can be most assured.

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HISTORICAL BACKGROUND

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The management of prostate cancer, as for any other disease, is guided by the natural history of the untreated and treated pathology as well as by the likely impact of the clinical disease on the life expectancy or quality of life of the individual patient. Therapeutic approaches are traditionally considered in relation to clinical stage as assessed by clinical examination, serum PSA levels, radiological and radioscintographic investigation.

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Before the effectiveness of hormone therapy was recognized over 60 years ...

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