Guidance conformance of mainstream germline cancer testing by oncology providers in the Veterans Health Administration.

e13571 Background: Mainstream germline testing, where oncology providers obtain consent and order testing directly, facilitates timely access to genetic testing for treatment decisions. The Veterans Health Administration promoted mainstreaming of a 62-gene multi-cancer germline testing panel for certain cancer diagnoses: breast, high-grade or metastatic prostate, ovarian/fallopian tube/primary peritoneal/serous uterine, pancreatic/ampullary adenocarcinoma, medullary thyroid, pheochromocytoma/paraganglioma, colorectal cancer diagnosed before age 50, and mesothelioma. We retrospectively evaluated conformance to guidance for adoption of mainstream testing. Methods: We analyzed all germline genetic tests ordered across VA facilities from February 2023 through December 2025. Test orders were categorized as conforming oncology (mainstream-eligible cancer diagnosis), non-conforming oncology (other cancer diagnosis), or non-oncology tests. For orders placed by oncology providers, clinical appropriateness was determined by ICD-10 code alignment with specified mainstream-eligible cancer types. Conformance to guidance was defined as ordering the 62-gene panel for patients with one of the specified mainstream-eligible cancer diagnoses. Primary outcome was rate of conformance to guidance in our mainstream testing model. Results: Among 13,339 genetic tests ordered by 204 providers across 143 facilities, 3,306 (24.7%) used mainstream testing and 10,033 (75.3%) used traditional genetics. Of mainstream orders, 3,130 (94.7%) were guidance conforming and placed by 109 providers, 161 (4.9%) were non-conforming oncology tests placed by 34 providers, and 15 (0.5%) were non-oncology tests placed by 10 providers. The most common conforming tests were in prostate (55.9%), breast (14.1%) and pancreatic cancers (6.6%), while the most common non-conforming tests with a documented indication were ordered in patients with family history of malignancy (12.1%), lung cancer (9.7%) and melanoma (4.8%). Conclusions: Our findings demonstrate that high fidelity to germline cancer genetic testing guidance by oncology providers is achievable under the mainstream model with 94.7% of testing conforming to guidance. This is critical to our understanding of the effectiveness of mainstreaming and the ability to replicate and scale-up mainstreaming in different health care settings.