Background: Precision medicine has changed treatment practices for patients with cancer, and clinical guidelines now recommend tumor marker testing. Studies have demonstrated that tumor marker testing increases use of appropriate targeted therapies which is associated with improved survival, particularly among patients with advanced or metastatic cancer. In March 2018, Medicare issued a national coverage determination (NCD) for next-generation sequencing to facilitate tumor marker testing. We conducted a retrospective study to assess tumor marker testing among Medicare beneficiaries with cancer from 03/01/2016 through 02/29/2020. Methods: Data were obtained from the Virtual Data Warehouses of 6 United States (US) healthcare systems in the Health Care Systems Research Network, a well-established distributed data network for cancer research. Together these systems provide care to a diverse population of over 5.5 million people in the US. The index date for each individual was the first observed cancer diagnosis date recorded in the tumor registry during the study period. Subgroup analyses included those with lung, breast, colorectal, or prostate cancers, or those with advanced, metastatic or recurrent cancer. This is part of a larger project that aims to advance methods for scalable and rigorous evaluation of outcomes of coverage policies for genetic tests. Results: We report initial results from three health systems (03/01/2016-02/29/2020) including Medicare beneficiaries ≥65 years and ≥90 enrollment days on/after the index date. There were 10,048 Medicare beneficiaries with cancer in the pre-policy period (48.2% were female and mean [SD] age was 75 [6.9] years), and 7,160 Medicare beneficiaries with cancer in the post-policy period (47.7% were women and mean [SD] age was 75 [6.8] years). In the pre-policy period, 15.4% had a tumor marker test on/after 90 days of the index date, which increased by 1.7% to 17.1% after the policy (p<0.0001); and 47.9% started a cancer drug therapy on/after 90 days of the index date, which increased by 4.1% to 52.1% after the policy (p<0.0001), adjusting for age and sex and cancer type. Among Medicare beneficiaries with advanced, metastatic or recurrent cancer, 20.9% had a tumor marker test within 90 days of the index date in the pre-policy period, which increased by 3.0% to 23.9% after the policy (p= 0.009), and 65.1% started a cancer drug therapy on/after 90 days of the index date, which increased by 6.3% to 71.4% after the policy (p<0.0001), adjusting for age, sex, Charlson score, and cancer type. Conclusions: Tumor marker testing rate among Medicare beneficiaries with cancer in these health systems increased after the implementation of the 2018 Medicare NCD. Analyses are underway to examine changes in tumor marker testing, cancer treatments, and outcomes among Medicare beneficiaries by cancer type after the implementation of the 2018 Medicare NCD.