Mainstream and fast-track genetic testing in pancreatic cancer patients and its impact on treatment: our experience in a tertiary hospital in Spain.

Pancreatic cancer (PC) is a highly lethal malignancy. 4-10% are linked to inherited mutations in genes such as BRCA1/2, PALB2, ATM and mismatch repair (MMR) genes. Germline testing is essential to guide treatment decisions, yet delays remain common. Genetic testing models without pre-test assessment in a Hereditary Cancer Unit (HCU), have emerged as a strategy to improve earlier clinical decision-making. A retrospective, observational and descriptive study was conducted on 223 PC patients (55% male; average age 64 years) who underwent rapid germline genetic testing at Hospital General Universitario Gregorio Marañón (Madrid, Spain) between April 2019 and May 2024. Tests were ordered by oncologists with brief pre-test counseling, followed by a nurse-facilitated consent and peripheral blood collection. Post-test counseling in an HCU was offered for patients with variants of unknown significance (VUS) and pathogenic/likely pathogenic variants (PV), or upon physician or patient request. PV and VUS were identified in 32 (14.3%) and 82 (36.7%) patients, respectively. 50% of PV carriers did not meet familial PC criteria. Actionable mutations were detected in 14 (43.7%) of PV carriers, involving BRCA2 (6/32), PALB2 (1/32) and ATM (7/32). Treatment modifications occurred in 7/223 patients (3%), including PARP inhibitors or platinum-based regimens. Median time from the genetic test request to the results was 48 days (95% CI, 44-52). Mainstream genetic testing in PC is a viable approach to expedite results and facilitate precision oncology. Further studies are needed to evaluate long-term outcomes, cost-effectiveness and the psychosocial impact compared to traditional genetic counseling pathways.