Germline testing in pancreatic adenocarcinoma: A retrospective cohort study of germline genetic testing uptake, patterns of referral, clinical findings and impact in the South Western Sydney Local Health District.

Abstract

115 Background: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival <12%. Universal germline genetic testing is recommended as pathogenic variants are identified in 8–15% of patients and guide therapy: BRCA1/2 and PALB2 predict platinum and PARP inhibitor sensitivity, while mismatch repair deficiency predicts immunotherapy response. Mutation detection rates in culturally and linguistically diverse (CALD) populations are not well described and may be influenced by inequitable access to genetic services. We evaluated germline testing patterns in PDAC patients within the culturally diverse South Western Sydney Local Health District (SWSLHD). Methods: Retrospective cohort study of PDAC diagnosed in SWSLHD (Jan 2020–Jun 2025). Data were extracted from electronic medical records and oncology databases. Variables included demographics, CALD status, tumour stage, referral pathway (mainstreaming vs genetics clinic), germline testing uptake and results, tumour molecular testing, treatment, and survival. Primary outcomes were germline referral and testing rates. Results: 60/300 diagnosed patients were analysed to date (data collection ongoing). 15/60 (25%) were referred for germline testing; 13/15 completed testing and 2/15 did not proceed (1 unclear, 1 deceased). Of those referred, 9/15 were Australian-born and 6/15 overseas-born; interpreter use was documented in 1 case. Family history of cancer was present in 8/15, absent in 3/15, and undocumented in 4/15. No patients underwent somatic next-generation sequencing and MMR testing was not routinely performed. No pathogenic variants were detected. 2/13 (15%) had variants of uncertain significance; both received genetic counselling and management did not change. Conclusions: Preliminary data demonstrate low germline testing rates (25%) within a highly diverse Australian population. The observed VUS rate (15%) is consistent with published literature (approximately 15–25%). Despite universal testing recommendations, implementation gaps remain. Ongoing data collection will determine whether overall pathogenic variant detection approaches expected rates (8–15%) and will inform strategies to improve equitable access to precision oncology in PDAC.