General introduction and thesis outline 11 The present thesis evaluates technological and clinical aspects of magnetic resonance (MR) imaging (MRI)-guided radiotherapy for the treatment of primary localised and locally recurrent prostate cancer. Considering the broadness of the topics discussed in this thesis, the following introduction offers a comprehensive overview of prostate cancer, with a focus on MRI-guided radiotherapy treatment for primary prostate cancer. Furthermore, MRI-guided focal salvage radiotherapy for the treatment of locally recurrent prostate cancer after primary radiotherapy is introduced. Epidemiology of prostate cancer Prostate cancer is the second most common cancer in men and the fifth leading cause of cancer death among men worldwide.1 In The Netherlands, prostate cancer is the most common type of cancer for men above 45 years of age, with about 12.500 new cases in 2020 (Figure 1).2 Approximately 1 in 9 men are diagnosed with prostate cancer over the course of their lifetime.3 The incidence rates vary greatly between countries, which is most likely due to international differences in diagnostic practices.4 In the late 1980s and early 1990s, incidence rates rapidly increased due to the introduction of prostate-specific antigen (PSA) testing, thereby detecting asymptomatic (preclinical) prostate cancer.5 In recent years, incidence rates have declined in many countries due to recommendations against the routine use of PSA screening. Whereas incidence rates continue to decrease in some countries, incidence rates have stabilised in recent years in others, including the United States, Denmark, and Norway.4–10 On the other hand, in many countries, such as China and Eastern Europe, incidence rates continue to increase, potentially due to increased awareness and improvements in healthcare systems in these countries.10,11 The increase in incidence was accompanied by an increase in prostate cancer-specific mortality in the early 1990s, after which the mortality rates steadily dropped, most likely as a result of advances in treatment and earlier detection.12–14 There is still little known about the aetiology of prostate cancer, although some risk factors have been established. These include age (prostate cancer is most frequently diagnosed among men aged 65-74 and is rarely seen in men below 40 years of age), family history of prostate cancer (especially when diagnosed before the age of 65), genetic mutations such as BRCA1 and BRCA2, and genetic conditions such as Lynch syndrome.1 Furthermore, Western African ancestry is thought to modulate the prostate cancer risk, with black males having the highest incidence rates.15 Due to early diagnosis, most patients (75-80%) have localised disease at presentation.16 Around 20% of the prostate cancer patients present withmetastasised disease, of whom approximately 65%with regional lymph node involvement only and 35%with distant metastases.16,17 Prostate cancer survival is high – in fact, prostate cancer survival is the highest of all cancers in the United States – with a 5year relative survival for all stages combined of 98%.14 However, the stage at diagnosis significantly impacts the relative survival, with excellent 5-year relative survival rates in patients with localised or regional disease (99.3-100%) and much worse 5-year relative survival rates of 32.3% in patients with distant metastases at presentation.17 1
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