Following the working program of the ENSAT-CANCER consortium between 2011 and 2016, yet unmatched progress has been achieved. This is exemplified by the large number of scientific publications, which can be summarized as follows:

Establishment and refinement of a virtual research environment (VRE) has been a major achievement that has welched together the consortium and has provided a common hub for scientific projects and clinical studies. An ever-growing number of patients has been collected with rich clinical annotations and wealth of biomaterial in the common registries and associated decentralized biobanks. The identification of patients with specific clinical characteristics has aided in recruitment of candidates for the clinical interventional trials. Similarly, the biomaterials and associated clinical data have been the basis of biomarker studies from the different work packages. A number of new functionalities have been implemented that include: 1) New search function with advanced notions of timeline representation, 2) Interactive completeness graphs to monitor and improve data quality, 3) Connection with American, Asian and Australian Adrenal Alliance (A5) registry, 4) Imaging support and 5) Robust mobile applications, that have full support on iOS and Android mobile devices.

Within the translational studies, important progress could be achieved towards the elucidation of pathways involved in adrenal tumorigenesis. These studies were able to identify new targets (such as SF-1 or the WNT/b-catenin pathway) that could result in therapeutic strategies. In fact, some of the gathered insights translated in novel treatment modalities, which were tested in studies in dedicated preclinical models.

Researchers forming the pathology platform made particular progress in the standardization of immunohistochemical techniques and interpretation of morphological tumour characteristics (including proliferation marker, extent of vascularization and content of cells with stem cell characteristics) required for comparison of adrenal cancer diagnosis and comparability of biomarker studies in the field across European countries.

For adrenocortical carcinoma, the genomic platform had achieved a major break-through with the first description of an integrative genomic approach. Since the molecular classification was achieved earlier than expected with the success of the integrated genomics of ACC it had been possible to develop molecular markers based on the analysis of methylation alterations in ACC during the last part of the program and to confirm the molecular classification in an independent international cohort. Likewise, epigenetic markers for the prediction of malignancy for pheochromocytomas could be identified which might aid in the differential diagnosis of this rare disease.

Significant progress has been made in our studies related to molecular target expression studies and studies on the relation between functional imaging (18F-FDG PET and MIBG) and genotype-dependent tumour cell energy metabolism, which provide the basis for further biomarker/functional imaging studies. First experience from patients with malignant pheochromocytoma enrolled in the FIRST-MAPPP study indicate potential discrepancy between morphological and functional imaging characteristics following tumour treatment.

Within the clinical study platform, the first randomized prospective trial on malignant pheochromocytoma has been moving forward with 45 centres being activated and 57 patients being randomized into the two study arms. Similarly, for the adjuvant treatment protocol of adrenal cancer patients a significant number of patients could be enrolled. Although the patient recruitment for both studies had been lower than anticipated in both instances the groundwork laid by the consortium made it possible to maintain the study in the recruiting clinical centres. Thereby, a successful completion of the clinical studies in the near future can be expected.