Representative trials are critical to advancing cancer treatment, yet little is known about how geographic siting contributes to non-representative enrollment. Using patient-level data, we determined how the choice of trial-enrolling regions and practices impacts representativeness. We created a SEER-Medicare cohort of people ≥65 years old with lung, breast, pancreatic, or renal cancer (2014-2019). We identified randomized cancer drug trial participants and determined the prevalence of age ≥75, sex, race, ethnicity, and rural residence in the full cohort, trial-enrolling regions, trial-enrolling practices, and trials. The choice of region and practice contributed to >
50% of the under-enrollment of Black, Hispanic, and rural patients. Cancer trials enrolled 45% fewer Black patients than expected with proportional representation. Trial recruitment in regions and practices with proportionately fewer Black patients accounted for 27% and 35% of this disparity, respectively. These findings suggest that diversifying cancer trials requires changing the regions and practices referring and enrolling patients.