Cancer is the second leading cause of death in Europe with an expected increase of about 25% by 2035. A wide and unacceptable variability in terms of access to research, innovation and quality care exists between and within countries. Possible solutions are an increase in knowledge by funding research, and a more equitable transfer of what we already know to everyone. Comprehensive Cancer Centers and Comprehensive Cancer Care Networks may be the core of CCIs that deliver quality care and provide resources to improve and integrate care, research and education. Data already available confirm that the level of "CCI maturity" in Member States is widely different, from some countries lacking CCIs completely. A European initiative, implemented in all Member States, based on a capacity building programme (CBP), will help reduce inequalities, in the context of other actions ongoing, such as CRANE, JANE and UNCAN. CBP is a complex intervention that requires multiple and integrated actions delivered to all the relevant stakeholders. CBP will be designed with an inclusive approach, tailored to the baseline status, capable of creating a change and improvement in research and care, with greater integration between them, supported by an education programme. It will operate at various levels: Individuals, Institutions and Systems. The CSA will implement the following steps: define CCI Maturity Model including quality indicators; profile the CCIs in each MS and a few ACs in terms of CCI presence and levels of maturity; design tailored CBP interventions, giving priority to MSs without any CCI; deliver online training courses open to teams in all MSs and ACs, implement targeted onsite interventions; scale up and sustain development; disseminate, exploit and report results. The CSA will maximize impact by bridging with the work of ongoing EU cancer research projects. National focal points will be key informants in making the links between the CSA, the EC and MSs.

Prostate Cancer is the most common cancer in European men. Despite dramatic improvements in early diagnostic and local treatment, one out of five prostate cancer patients will die from their disease. Despite progress in the past years, it remains critical to improve on the present strategy for advanced and metastatic prostate cancer. Within the proposed project, we will evaluate whether intermittent intensified androgen deprivation treatment (iADT) in metastatic prostate cancer is not inferior to continuous treatment in terms of oncological benefit while minimizing side effects and resource utilization and improving patient quality of life. The proposed clinical trial is designed to detect early if iADT has a negative impact on overall survival compared to continuous therapy. If successful, the outcomes of the project will define a new evidence-based standard of care for metastatic hormone sensitive prostate cancer. The proposed research could lead to improved patient survival and quality of life but also improve health system sustainability. This is a multidisciplinary and multistakeholder consortium involving clinical oncologists, surgeons, health economists and patient representatives. The study design was successfully discussed with patients. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.

MyPeBS addresses the crucial and timely question of the future of breast cancer screening in Europe. Indeed current standard mammographic screening, with entry stratified by age alone, has recently been largely questioned. Despite a demonstrated mean 20% reduction in breast cancer-specific mortality, together with reduction of late-stage disease in women older than 50, it is associated with potential harms including false positive recalls and over-diagnosis. Individual breast cancer risk estimation, through models including clinical variables, mammographic breast density and more than 100 genetic polymorphisms, now has substantial clinical and scientific bases. Personalized screening strategies, based on individual risk levels, could potentially improve the individual benefit/harms ratio of screening (earlier cancer detection and less intensive treatments in high risk women, less false positives and over-diagnoses in low risk ones), and increase the cost-efficacy for health insurances. MyPEBS will conduct an international randomized phase III trial to validate this hypothesis. It will primarily assess the ability of an individual risk-based screening strategy to be non-inferior, and possibly superior, to the standard of care screening, in reducing the cumulative incidence of stage II+ breast cancers. The trial, conducted in 5 countries (France, Italy, UK, Belgium and Israel) will include 85000 European women aged 40-70, all followed for 4 years. MyPEBS will also evaluate if an individual risk-based screening strategy, compared with the standard, reduces screening-related harms (unnecessary biopsies, overdiagnoses) in low-risk women, is overall at least as cost-effective as well as more accepted by women resulting in a larger screening coverage. After analyses of all components, the final objective of MyPEBS is to deliver recommendations for the best future breast cancer screening strategy in Europe.

Over the past 5 years, antibody drug conjugates (ADCs) have shown impressive improvements in survival outcomes of solid tumors and hematological malignancies. With 14 ADCs already approved across different countries and more than 140 that entered the clinical development, they are intended to replace standard chemotherapies across multiple tumor types over the next decade. Although ADCs show great clinical efficacy, resistance eventually occurs, and it becomes critical to understand resistance mechanisms to guide the choice of the following lines of therapy for patients who progress on a given ADC. Given the complex nature of ADCs, immunocompromised mouse models (nude mice, NOD-SCID or NOG mice) and currently used clinical assays (standard radiology, IHC, WES etc) are not the optimal preclinical and clinical tools, to identify the multiple causes of resistance. The OASIS project aims to generate a biobank of different patient-derived organoids (PDOs), which better recapitulate ADCs resistance and integrate different assays, spanning from whole-body molecular imaging (Ab-radiolabeled PET scan or immunoPET), circulating tumor cells (CTC), plasma proteomics, to multiplex immunofluorescence (MIF) and machine-learning enhanced digital pathology (AI-digital pathology) to capture most of the parallel mechanisms of resistance to ADCs. Such tools will enable to define biomarkers of ADC resistance that can inform further therapeutic decisions.

Worldwide, ~7 million women live with or beyond Breast Cancer (BC), as 10-year survival rates exceeding 80% for early-stage (I-III) BC. Premenopausal BC accounts for 25% in the EU and 55% in low/middle income countries. Most premenopausal women with BC have high risk of recurrence, therefore standard treatment includes adjuvant chemo- (CT) and endocrine therapy (ET). However, treatment has substantial physical, emotional and social burden, which is often more pressing for younger compared to older patients. Gene-expression assays are used for post-menopausal patients to identify women who can safely forego CT without detriment on clinical outcomes, preserving Quality of Life (QOL). However, a definitive study has yet to be conducted among premenopausal women with high-risk HR+HER2-BC. The primary objective of PATH-FOR-YOUNG is to conduct a pragmatic randomized controlled trial (RCT) with 5000 patients validating the use of a gene-expression assay to drive adjuvant treatment decisions in this target population. PATH-FOR-YOUNG aims to achieve its objective in 7 years. The project (i) builds on and complements an ongoing twin RCT to ensure timely recruitment, (ii) leverages on a large international consortium of oncologists, pathologists, patient representatives, psychologists, sociologists, ethics and communication experts, biostatisticians, health economists, and technology providers, to assure complementary and multidisciplinary expertise, and (iii) highlights patient-engagement, participatory care, and early involvement of end users. PATH-FOR-YOUNG will also study implementation of digital self-management to support patients throughout the cancer journey and particularly while on ET to improve QOL and medication adherence. A full HTA will ensure a path towards cross-country implementation. PATH-FOR-YOUNG has the ambition to improve BC care, fully integrating the predictive, personalized, preventive, and participatory principles of health management.