Introducing PIONEER : a project to harness big data in prostate cancer 2 research 3 4

48 PIONEER (Prostate Cancer DIagnOsis and TreatmeNt Enhancement through the power of big 49 data in EuRope) is a European network of excellence for big data in prostate cancer, consisting 50 of 32 private and public stakeholders from 9 countries across Europe. Launched by the 51 Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme 52 (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate 53 cancer management by unlocking the potential of big data. 54 The project has identified critical evidence gaps in prostate cancer care, via a detailed 55 prioritisation exercise including all key stakeholders. By standardising and integrating 56 existing high quality and multidisciplinary data sources from prostate cancer patients 57 across different stages of the disease, rich big data will be assembled into a single 58 innovative data platform for research. Based on a unique set of methodologies, PIONEER 59 aims at advancing the field of prostate cancer care with particular focus on improving 60 prostate cancer-related outcomes, health system efficiency by streamlining patient 61 management, and the quality of health and social care delivered to all prostate cancer 62 patients and their families. The literature suggests there is underuse of effective 63 treatments and overuse of ineffective treatment. For example, androgen deprivation 64 therapy is sometimes overused in situations where it is not recommended. It is therefore 65 crucial to identify the best treatment option for the individual patient. 66 Introduction 67 68 Prostate cancer is the second most common cancer in men by incidence in Europe, with 69 450,000 new cases diagnosed in 2018. Prostate cancer incidence varies five-fold, with the 70 highest incidence in Northern and Western Europe, and the lowest in Central and Eastern 71 Europe. The estimated incidence is highest in Ireland (189.3 per 100,000), whereas Albania 72 (37 per 100,000) and Romania (47.2 per 100,000) have the lowest incidence (1). In 2018, the 73 estimated numbers of death of prostate cancer were 107,300 for Europe (40 European 74 countries), and 81,500 for 28 members countries of the European Union (1). Total annual 75 estimated costs for treatment of prostate cancer in the first year following diagnosis is 76 approximately €117 million in the UK. The figure is twoto three-fold higher in France and 77 Germany (2). This economic burden associated with prostate cancer is predicted to 78 dramatically increase in the coming years due to aging of the population, as around 85% of 79 all cases of prostate cancer are diagnosed in men over the age of 65 years (1, 3, 4). Despite 80 these numbers, up to now the level of funding for research is relatively low. For example, in 81 2018/2019, Cancer Research UK spend £13 million on prostate cancer research out of their 82 total annual budget of £442 million (5). Therefore, progress made in prostate cancer research 83 is limited when compared to other major cancer types. (1) For example, mortality statistics of 84 Cancer Research UK indicate the mortality rate of breast cancer has been steadily declining, 85 while the prostate cancer mortality rate is still on the rise (5). 86 87 Currently, several critical questions remain unresolved regarding the screening, diagnosis and 88 treatment of prostate cancer patients, relating to various observations in prostate cancer 89 epidemiology. First, prostate cancer incidence is variable across different European countries 90 (37 to 189 per 100,000) (1). The differences in incidence rates of different racial and ethnic 91 background confirms the involvement of genetic factors. However, environmental factors 92 may also be implicated as the differences are also observed among men of the same genetic 93 heritage who live in different European countries. Furthermore, inequalities in prostate 94 cancer survival are also observed across the European Union. Estonia and Latvia have the 95 highest mortality rates (37.3 per 100,000 and 35.7 per 100,000 respectively), whereas the 96 mortality rates are the lowest in Spain and Italy (13.2 per 100,000 and 10.7 per 100,000 97 respectively) (1). 98 99 A variety of risk factors have been scrutinized for prostate cancer, including metabolic 100 syndrome, obesity, dietary and genetics (6). However, the evidence on risk factors for 101 prostate cancer remains inconclusive and, importantly, knowledge is lacking regarding patient 102 characteristics (including molecular characterization) for optimal stratification of patients at 103 time of diagnosis (6). Several diagnostic and prognostic tests for prostate cancer based upon 104 molecular biomarkers have emerged, leading to a real challenge how to assess and prioritise 105 these biomarkers (7). . Moreover, the variable pattern of prostate cancer screening and 106 Prostate-specific antigen (PSA) testing across countries hinders a meaningful interpretation 107 of available epidemiologic studies on the main risk factors for prostate cancer. Lithuania is 108 among the few countries in the world where there is a national prostate cancer screening 109 programme since 2006 (8). However, prostate cancer screening is considered one of the most 110 controversial topics in urology, as there are different thresholds for screening frequency and 111 intervals, and PSA thresholds for biopsy (9). This lack of knowledge means that safe 112 identification of the candidates for active surveillance is suboptimal and similarly, predicting 113 which patients will respond better to specific treatments remains difficult (6, 10). 114