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

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.

FIGURE 1

A timeline of the Tumor‐First implementation project and its' activities.

FIGURE 2

The genetic testing practices amongst OC patients over the years; either a tumor DNA test first, a germline test first or no genetic testing at all. The Tumor‐First pathway is further detailed to illustrate the percentage of patients who have completed genetic testing through this flow. Year‐to‐year differences were compared by Fisher's Exact Test (germline test after unsuccessful tumor DNA test) or Chi‐square tests (in all other situations). The expected percentages for 2023 (“23exp) were calculated based on the percentages of patients from 2022 who were tested in the following year. ^#This includes 419 patients who received only germline testing, 161 patients who received the germline test first followed by a tumor DNA test, and 55 patients who received both tests in parallel (<14 days in between). Two germline tests, and 7 tumor DNA tests were unsuccessful. ^‡180 (8%) patients without a tumor PV received germline testing. OC, ovarian carcinoma, PV, pathogenic variant.