Contents:

TABLE OF CONTENTS Our HEALTHCARE 2 About the oncology pharmaceutical analysis team 2 Casodex 150mg withdrawn for the treatment of localized disease 3 EXECUTIVE SUMMARY 4 Prostate Cancer Insight: methodology 5 Prostate Cancer Insight: key conclusions 6 The widespread introduction of PSA screening in Europe will occur over the next 10 years, leading to a US-style stage migration. Companies with marketed or developmental prostate cancer products must target the larger localized and recurrent disease populations that will result 7 Traditionally, total androgen blockade (TAB) has been shunned by urologists. However, new literature reviews are now challenging physicians’ preconceptions and changing prescribing habits in favor of TAB, producing a niche market for low toxicity anti-androgens 11 The average age of Japanese patients is higher than in Western markets. This means that aggressive therapy is often contraindicated. Consequently, more patients receive drug-based therapy, producing a deceptively large drug market that should be targeted by manufacturers 15 Intermittent hormonal therapy (IHT) may provide an improvement in efficacy and side effects over continuous hormonal therapy. Manufacturers of hormonal products must consider how they may capitalize on the uptake of IHT if current trials show an advantage to the new treatment strategy 16 Summary of points: the prostate cancer market to 2015 21 INTRODUCTION 28 The prostate 29 Prostate cancer 30 Histology 30 Etiology 31 Epidemiology 33 Incidence forecasts 35 Point prevelence forecasts 36 SCREENING, DIAGNOSIS AND STAGING 37 Screening 37 Prostate cancer screening 37 Summary and comments 43 Diagnostic methods 44 Staging 45 Clincal staging 45 Gleason grade 48 Physician data 50 Screening 50 The effect of screening on presentation pattern 54 Diagnosis and staging tests 57 TREATMENT OF LOCALIZED DISEASE 62 New and old treatment options for localized disease 62 Watchful Waiting 63 Surgery for localized disease 65 Radical Prostatectomy 65 Cryotherapy 69 Radiotherapy for localized disease 70 Brachytherapy 71 External beam radiotherapy 80 How effective are 3DCRT and IMRT? 81 Toxicity of 3DCRT and IMRT 83 Adjuvant hormonal therapy 85 Hormonal therapy 86 Summary 94 Physician data 95 Watchful waiting 95 Surgery 98 Radiotherapy 107 Drug Therapy 123 Disease outcome for localized prostate cancer 142 TREATMENT OF LOCALLY ADVANCED DISEASE 146 Treament options for locally advanced prostate cancer 146 Regional variation in treatment patterns 147 Surgery 147 Hormonal therapy alone 149 Radiotherapy 155 Summary 159 Physician data 161 Choosing no treatment 161 Surgery 163 Radiotherapy 169 Drug therapy 176 Disease outcome for locally advanced prostate cancer 184 TRIAL IL0025 AND ITS SIGNIFICANCE 189 The Casodex trials 189 Data from IL0025 and the European and US trials 190 The reaction from physicians 193 Interpretation of the IL0025 results 194 Action taken by urologists in affected markets 195 Possible impact on US approval 196 The effect of IL0025 on Casodex sales 197 FUTURE CHALLENGES FOR CASODEX 199 Regaining approval in localized prostate cancer 199 Summary 204 SUPPORTING DATA 205 Duration of first-line drug therapy and progression factors 205 Second-line drug therapy 209 APPENDIX A 215 Contributing experts 215 List of tables 216 List of figures 225 Bibliography 232 Physician research methodology 266 Introduction 266 Our research partners 268 Research objectives 268 Questionnaire development 271 Research methodology 272 Data processing 274 Quality control 275 Opinion Leader research 276 Prostate Cancer Insight Questionnaire 278 OncoVision 308 APPENDIX B: Our 309 Our 309 Our Healthcare 309 Our Healthcare research and analysis methodologies 310 Our Healthcare therapy area capabilities 310 About the Oncology analysis team 311 Our Healthcare Consulting expertise 312 Disclaimer 314