With Europe’s Beating Cancer Plan (EBCP), the European Commission follows a new approach to cancer prevention, treatment and care. The action ‘OBS-Learning From Progress In Addressing Cancer In Europe’ (OBS-PACE) contributes to this by improving the understanding of the national cancer control situation and policy actions in EU Member States.
OBS-PACE is collecting case studies of innovative actions in cancer research, care, and policy across the cancer care pathway. The case studies mirror the implementation of the EBCP at the national and regional level and can inform new actions to better tackle cancer across Europe. Each case study describes the objective of the new action, its implementation, including enablers and barriers, and its outcomes at the health system level.
24 March 2025 | Case Study
In the Netherlands, approximately 3% to 5% of patients with metastatic disease have cancer of unknown primary (CUP), where the origin of the tumour remains unidentified despite advanced imaging techniques and comprehensive pathology workups. This lack of clarity often leads to long diagnostic delays and limited treatment options, resulting in poor clinical outcomes for these patients (Fuereder, 2024). Recent large-scale genome sequencing studies have demonstrated that distinct patterns of somatic variants and other genomic characteristics can help predict tumour types. Notably, actionable genomic events have been identified in nearly half of CUP patients (Schipper et al., 2022). CUP is recognized as one of the deadliest forms of cancer in the Netherlands, and until recently, patients had no access to genomic sequencing diagnostics for this condition.
In light of these findings, the patient advocacy group “Missie Tumor Onbekend” initiated systematic awareness and advocacy activities between 2020 and 2021. These efforts have spurred significant advancements in access to diagnostic capabilities, ultimately enhancing treatment options for CUP patients.
Advocates from “Missie Tumor Onbekend” have actively lobbied for improved access to whole genome sequencing (WGS) for patients with cancer of unknown primary (CUP). Their outreach targeted key stakeholders in the healthcare system, including providers, diagnostics companies, insurance funds and policymakers. This comprehensive approach was deemed essential for enhancing health outcomes for CUP patients. The advocates developed a compelling (business) case using data from the national cancer registry, which included Dutch CUP mortality statistics, statistics on health service use for CUP patients versus patients with metastases from known primary tumours, early data from clinical trials implementing WGS in routine care and the cost-effectiveness of early molecular diagnostics. They demonstrated that implementing molecular profiling early could prevent higher costs associated with other diagnostic methods. By effectively representing the patient voice and leveraging scientific evidence, they guided discussions around reimbursement decisions. They led policy dialogues and awareness campaigns, emphasizing the low survival rates and limited quality of life associated with CUP.
As a result of these advocacy efforts, the case for nationwide reimbursement for whole genome sequencing (WGS) diagnostics for CUP via designated clinics equipped for molecular tumour profiling and capable of interpreting test results was presented at a parliamentary hearing in February 2021 (Tweede Kamer, 2021). During the hearing, access to extensive genomic profiling for all cancer patients with metastases was debated. Several motions (including one specifically on access to WGS for CUP) were voted on. The positive response on the motion for CUP led to the reimbursement for WGS for CUP via specialized clinics adopted in April 2021 (Nederlandse Zorgautoriteit, 2021).
These eight Dutch tertiary cancer referral centres, first of all, have a molecular tumour board in place (Koopman et al., 2021) and consequently have been designated as CUP clinics, with specialized teams trained in recognizing and treating various CUP-classified conditions (Amsterdam University Medical Center, Erasmus Medical Center, Leiden University Medical Center, Maastricht University Medical Center, Netherlands Cancer Institute, Radboud University Medical Center, University Medical Center Groningen and University Medical Center Utrecht). Furthermore, the National Cancer Institute and other professional and scientific organizations are actively involved in developing diagnostic protocols and guidelines for patients with CUP (DI-CUP protocol, 2022). By the end of 2025, the updated clinical guideline on CUP should be published, including the diagnostic, treatment, aftercare and the organization of care for the patients with CUP.
Enablers: Initially, scientific organizations were sceptical of the advocacy efforts. However, the evidence-based approach, which used data from the national cancer registry, effectively highlighted the challenges faced by patients with CUP. This data-driven advocacy ultimately fostered collaboration on the development of national protocols and guidelines. The initial concerns regarding funding constraints were also addressed through compelling data on the provision of diagnostics for CUP patients from other settings and countries. This evidence helped to shift perspectives and secure support for necessary financial resources. To implement these actions successfully, further workforce and skills development were essential. While health professional organizations contributed to these developments, additional funds were required to support this skills enhancement.
For instance, the decision to incorporate whole genome sequencing (WGS) diagnostics for CUP has yielded positive results (Samsom et al., 2022). Approximately 80% of CUP patients who underwent WGS benefited from molecularly guided therapy based on their tumour and gene profiles, whereas before they didn’t even have a diagnosis that would make them eligible for advanced pain management services. Notably, actionable targets were identified in 70% of these patients as a result of this sequencing effort (van Putten et al., 2023). Thus, advocacy and their highly possible participation in the health policy making led to improvements in access to diagnosis and consequently to care, touching on health system functions such as financing (here – inclusion of services in the benefit basket) and resource development and use (genomics-based capacity building, etc.). Ultimately, this translated into more equitable access to care for patients with CUP and, consequently, seeks to contribute to improved health outcomes.
Lessons learned: First, a culture that embraces patient advocates and values their neutral, constructive voice fosters meaningful change. This was evident in the Netherlands, where advocates for CUP patients achieved significant results by prioritizing data and an evidence-based approach. Their work with national cancer registries and cost-effectiveness data built a compelling case for reimbursement of whole genome sequencing. These developments inspired similar efforts in other regions, such as Belgium, and for other diseases.
For further details on this case study, please reach out to obs-pace@obs.who.int.
DI-CUP protocol (2022) Available at: https://www.nvmo.org/wp-content/uploads/2022/01/DI-protocol-CUP_versie-2.0.pdf (accessed 29 November 2024).
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Schipper, L.J., Samsom, K.G., Snaebjornsson, P., Battaglia, T., Bosch, L.J.W., Lalezari, F., Priestley, P., Shale, C., van den Broek, A.J., Jacobs, N., Roepman, P., van der Hoeven, J.J.M., Steeghs, N., Vollebergh, M.A., Marchetti, S., Cuppen, E., Meijer, G.A., Voest, E.E., Monkhorst, K., 2022. Complete genomic characterization in patients with cancer of unknown primary origin in routine diagnostics. ESMO Open 7, 100611. https://doi.org/10.1016/j.esmoop.2022.100611.
Tweede Kamer, 2021. VAO Initiatiefnota van de leden Sazias, Van den Berg en Veldman over urgentie invoering uitgebreid persoonlijk profiel (35383) [WWW document]. URL https://www.tweedekamer.nl/debat_en_vergadering/plenaire_vergaderingen/details/activiteit?id=2021A01080 (accessed 29 November 2024).
van Putten, J., Koster, R., Snaebjornsson, P., van Wezel, T., Bosch, L.J.W., Cuppen, E., Monkhorst, K., 2023. 1249P Whole genome sequencing-based cancer diagnostics in routine clinical practice: An interim analysis of two years of real-world data. Ann. Oncol. 34, S727. https://doi.org/10.1016/j.annonc.2023.09.2338.
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