The diagnostic and therapeutic landscape for high-risk localised prostate cancer and synchronous metastatic hormone-sensitive prostate cancer (mHSPC) is rapidly evolving, driven by advances in imaging, risk stratification and systemic therapies, including the advent of precision medicine. High-quality real-world data integrating clinical, imaging, molecular, quality-of-life information and outcome data remain scarce. The PROspective Prostate Cancer Infrastructure (ProPCI) is a nationwide, multicentre observational cohort designed to collect comprehensive longitudinal data and biomaterials to support real-world evidence generation, facilitate biomarker discovery and enable future cohort multiple randomised controlled trials (cmRCTs).

ProPCI includes adult men with high-risk localised prostate cancer or synchronous mHSPC across hospitals in the Netherlands. Clinical data are extracted from electronic health records using a standardised protocol and linked to national registries and healthcare use datasets. Patient-reported outcome measures are collected at baseline and regular intervals using validated instruments. Serial blood samples are biobanked for circulating tumour DNA and other molecular analyses. Outcomes include diagnostic and treatment patterns, Prostate-specific antigen kinetics, time to castration-resistant prostate cancer, radiological and clinical progression, health-related quality of life trajectories and healthcare use, including expenditure and exploratory biomarker associations. Statistical methods include descriptive analyses, time-to-event models, mixed-effects models and biomarker-outcome correlates.

Ethical approval has been obtained from the Committee on Research Involving Human Subjects (CMO) of Radboudumc. Written informed consent will be obtained from every participating patient and covers: (1) extraction and linkage of clinical, imaging, pathology and registry data, (2) future contact for potential cmRCT participation; and optional components (3) quality-of-life questionnaires, (4) collection of additional blood samples and (5) use of biomaterials for genomic testing. Results will be disseminated through peer-reviewed publications.

NCT07560748.

Growing evidence suggests that a part of the burden of Parkinson’s disease (PD) can be explained by exposure to environmental factors, including pesticides, heavy metals, solvents, and air pollution. However, several questions remain unanswered, pertaining to the associations with PD of environmental factors that are still in use today; the added risks of co-exposure to multiple environmental factors and gene–environment interactions. Additional questions remain on the relevant time window, duration, and level of environmental exposures in relation to PD risk. Furthermore, it is unclear whether these exposures are associated with clinical progression of PD.

PD-PEST (Parkinson’s Disease–Preventing Emergence of Symptoms by environmental Toxicants) is a nationwide hospital-based case–control study conducted in the Netherlands. The study population consists of 1500 persons with a recent PD diagnosis and 3000 age- and sex-matched controls. Participants will be recruited from four regions across the Netherlands to ensure a representative geographical distribution in terms of urbanisation, industry, and agricultural activity. Cases must have a PD diagnosis, established by a neurologist in the Netherlands according to standard diagnostic criteria. Controls are outpatients with a different neurological condition that is unlikely to be associated with the environmental factors of interest or the risk of PD. We will collect detailed information on historical and current environmental exposures at an individual level. This includes occupational and residential histories (via questionnaires and nationwide registries) and measurements (blood, saliva, faeces, hair, and via silicone wristbands). Based on these multimodal data, we will estimate participants’ individual lifetime exposure to environmental factors. Then, we will examine the associations between these exposures and the risk of PD. In addition, we will assess longitudinal associations between exposures and clinical progression of individuals with PD over 36 months. Analyses will be adjusted for possible confounders and multiple hypothesis testing.

The PD-PEST study aims to overcome the limitations of previous studies by examining a large, representative study population, incorporating detailed information on clinical PD diagnosis, conducting extensive assessments of historical and current environmental risk factors and collecting detailed information on possible confounders. The results are expected to enhance our understanding of the role of environmental factors in the aetiology of PD and inform preventive strategies.

The Medical Ethical Committee Oost-Nederland approved this study (NL86526.091.24). Informed consent will be obtained from each participant prior to participation in any of the study procedures. Findings of this study will be disseminated through publications, conferences, stakeholder briefings, and tailored communication materials for participants and the wider Parkinson community.

Open Science Framework, January 2025 (osf.io/4q9vs).