Nationwide implementation and evaluation of the Tumor-First workflow for genetic testing in ovarian carcinoma

Int J Cancer. 2025 Aug 1;157(3):504-512. doi: 10.1002/ijc.35440. Epub 2025 Apr 16.

Abstract

Despite international agreement on the importance of tumor DNA testing and germline testing for determining PARP inhibitor treatment eligibility in patients with ovarian carcinoma (OC) and for cancer prevention in their relatives, the optimal strategy remains under debate. In the Netherlands, the "Tumor-First workflow" was initiated and implemented nationwide: a well-validated tumor DNA test is the primary test for detecting tumor pathogenic variants (PVs) in OC risk genes (BRCA1/2, RAD51C/D, BRIP1, PALB2). The detection of tumor PVs is subsequently used to stratify germline testing and determine treatment eligibility. The Tumor-First workflow is efficient and saves costs. The aim of this study was to evaluate the nationwide implementation of the Tumor-First workflow. We analyzed real-time genetic testing practices, including tumor DNA and germline testing, in patients diagnosed with OC from 2019 to 2023, as identified through the Dutch Pathology Registry (Palga). Testing data were collected from diagnostic pathology and genetic reports. Out of the 3926 OC patients, 2778 (71%) received OC tumor DNA testing as the primary test. Between 2019 and 2023, this percentage increased from 50% to 85%. Of these tumor DNA tests, 2703 (97%) were successful, with 398 (15%) resulting in the identification of a PV in an OC risk gene. Most of these patients (291; 73%) underwent germline testing, and 147 (51%) were found to have a germline PV. We conclude that the nationwide implementation of the Tumor-First workflow for OC was effective. Multidisciplinary efforts contributed to a more efficient detection of germline and somatic PVs in OC risk genes.

Keywords: BRCA; epithelial ovarian cancer; implementation; neoplasm DNA; workflow.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing* / methods
  • Genetic Testing* / statistics & numerical data
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Netherlands / epidemiology
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / genetics
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • RNA Helicases
  • Workflow

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • BRCA1 protein, human
  • PALB2 protein, human
  • BRCA1 Protein
  • Fanconi Anemia Complementation Group N Protein
  • BRIP1 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors
  • RNA Helicases
  • Fanconi Anemia Complementation Group Proteins