Opportunities to improve detection of genetic predisposition for ovarian cancer applying the Tumor-First workflow

Genetic testing in ovarian carcinoma (OC) patients is very important for patients and their relatives. The Tumor-First workflow uses a tumor DNA test to stratify germline testing for hereditary cancer predisposition as well as treatment options with PARP inhibitors. This workflow is adopted and successfully implemented nationwide. Here, we evaluated recent tumor DNA testing rates in the Netherlands to identify untested OC patient groups and optimize tumor DNA testing rates. OC patients diagnosed in 2023 or 2024 were selected from the Netherlands Cancer Registry. We analyzed patient characteristics associated with the likelihood of tumor DNA testing using multivariable logistic regression. Tumor-First testing was performed for 1765 out of the 2221 (79%) OC patients. Patients diagnosed with advanced stage OC were more likely to receive tumor DNA testing (OR = 2.5, p < 0.001) than those with low-stage disease. Compared with patients who underwent surgery as primary treatment, those who received chemotherapy or no primary treatment were less likely to be tested (OR = 0.21 and OR = 0.07, respectively, p < 0.001). Patients who died within 100 days were less likely to receive testing (OR = 0.57, p = 0.003). Patients without resection after diagnosis on biopsy/cytology had the lowest Tumor-First testing rates (58% vs. 87-95%, χ2 p < 0.001). Tumor-First testing rates are high. However, OC patients that do not undergo a resection are less likely to undergo testing. With these data strategies to identify hereditary cancer predisposition in patients and their relatives can be further improved.