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Imaging and Treatment Outcome of Potentially Curable Prostate Cancer

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Imaging and Treatment Outcome of Potentially Curable Prostate Cancer I dedicate this book to my family and my parents, who left us very early. Their absence has left me and my sisters in great grief. List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Sandblom G, Ladjevardi S, Garrmo H, Varenhorst E. The Impact of Prostate-specific Antigen Level at Diagnosis on the Relative Survival of 28,531 Men With Localized Carcinoma of the Prostate. II Ladjevardi S, Berglund A, Sandblom G, Varenhorst E. Tumour grade, Treatment, and Relative Survival in a population-based cohort of Poten- tially Curable Prostate Cancer. III Ladjevardi S, Berglund A, Bratt O, Widmark A, Varenhorst E, Sand- blom G. Treatment with curative intent, and survival in men with high- risk prostate cancer. A population-based study of 11,380 men with se- rum PSA 20-100 ng/ml. IV Ladjevardi S, Wies J, Sörensen J, Häggman M, Tolf A, Jorulf H. Imag- ing of the prostate to indicate the areas for targeted biopsy Reprints were made with permission from the respective publishers Contents Introduction...................................................................................................11 Background ..............................................................................................11 Aetiology..................................................................................................12 Incidence ..................................................................................................13 Normal anatomy and histology of the prostate ........................................16 Neuraoanatomy ........................................................................................17 Histology of prostate cancer and the Gleason Score................................18 Symptoms.................................................................................................20 Prostate-specific antigen PSA ..................................................................20 Diagnosis..................................................................................................20 Staging......................................................................................................21 Imaging ....................................................................................................22 Management.............................................................................................23 Management of localised PCa..................................................................24 Expectancy ...............................................................................................25 Management of locally advanced PCa .....................................................26 Management of generalised PCa .........................................................27 Quality of life ...........................................................................................27 Randomised studies..................................................................................28 Register Studies........................................................................................29 Population-based study design ............................................................29 Aims of this thesis.........................................................................................30 Material and methods....................................................................................31 Studies I-III ..............................................................................................31 The Swedish Cancer Register..............................................................31 National Prostate Cancer Register (NPCR) of Sweden .......................31 The Swedish Cause of Death Register.................................................32 Study IV ...................................................................................................32 Statistical analysis ....................................................................................33 Study I..................................................................................................33 Study II ................................................................................................33 Study III...............................................................................................33 Study IV...............................................................................................34 Ethical considerations ..............................................................................34 Results...........................................................................................................35 Study I ......................................................................................................35 Study II ................................................................................................40 Study III...............................................................................................45 Study IV...............................................................................................48 Discussion.....................................................................................................51 Study I ......................................................................................................51 Study II.....................................................................................................52 Study III ...................................................................................................54 Study IV ...................................................................................................57 General discussion ........................................................................................59 Conclusion ....................................................................................................62 Swedish summary (Sammanfattning på svenska).........................................63 Slutsatser ..................................................................................................65 Recent Development and Future Perspectives..............................................67 Acknowledgements.......................................................................................70 Referens: .......................................................................................................72 Abbreviations ADT Androgen deprivation therapy ADC Apparent diffusion coefficient AS Active surveillance CCI Charlson Co-morbidity Index CI Confidence intervals CNB Core needle biopsy DRE Digital rectal examination DW Diffusion-weighted GS Gleason Score HR Hazard Ratio LPR Laparoscopic radical prostatectomy MRI Magnetic resonance imaging MRSI Magnetic resonance spectroscopic imaging NA Not applicable NNT Number of men needed to treat NPCR National Prostate Cancer Register NPR National population Register PCa Prostate cancer PET Positron Emission Tomography PSA Prostate specific antigen RP Radical prostatectomy RS Relative survival RT Radiation therapy SCDR The Swedish Cause of Death Register SCR The Swedish Cancer register SPCG-4 Scandinavian Prostate Cancer Group Study Nr 4 TNM Tumour Node Metastasis TRUS Transrectal ultrasonography WW Watchful waiting Introduction The aim of the present thesis was to investigate the potential benefit of cura- tive treatment compared with conservative treatment for men with the ag- gressive prostate cancer. The first study reports the concern required for men with prostate-specific antigen in the lowest range. In the second study rela- tive survival in a large, unselected, population-based cohort of men with potentially curable prostate cancer is assessed. In third study focuses on treatment modalities in relation to cause-specific mortality in a large unse- lected population-based cohort of men with prostate cancer and serum pros- tate-specific antigen levels between 20 and 100 ng/ml. The fourth study ex- plores the effectiveness of Magnetic Resonance imaging and Positron Emis- sion Tomography imaging techniques in planning the prostate biopsy. Background The prostate was first described by the Venetian anatomist Niccolò Massa in 1536, and illustrated by the Flemish anatomist Andreas Vesalius in 1538. Prostate cancer (hereafter referred to as ´PCa´), however, was not identified until 1853. PCa was initially considered a rare disease, probably because of shorter lifespan and poorer detection methods in the 19th century. At the beginning of 19th century, George Langstaff described PCa for the first time in the UK [1]. Towards the end of the 19th century Von Recklinghausen observed that the primary prostatic focus was often small and insignificant in comparison to the numerous and often far advanced bone metastases [2], which led to PCa being considered a disease with the potential to metastasise to the skeleton. PCa is the most common malignancy among males in the western World. It accounted for almost 36% of cancer diagnoses among men in Sweden in 2009 [3]. With its high incidence and the development of new and techni- cally advanced forms of management, PCa has also become a substantial financial burden for society [4]. The total cost of PCa in Sweden increased from 20 million euros in 1991 to 65 million euros in 2002 [5]. A high pro- portion of these costs are incurred during the first year after diagnosis; in 2006, this amounted to between 106.7 and 179.0 million euros (€) in the European countries where these data are available (Italy, Spain, UK, France, 11 and Germany). In the USA, the total estimated
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