Simple SummaryDay-to-day function in people with a history of cancer is incredibly important. It tells us what symptoms need to be treated, helps providers refer patients for rehabilitation, and helps us understand who is at risk of losing function. Our study looked at over 300 people with many different cancers, from five cancer centers in the United States. We found that people with active brain, sarcoma, prostate, and lymphoma cancers had the lowest function among people who were receiving rehabilitation. When cancer was cured, function was not related to the type of cancer someone had. Also, older people, overweight people, and people with non-cancer issues (like arthritis) had lower function. The results are the first of its kind to be reported and can lead to better decision-making for oncologists referring patients to rehabilitation care.AbstractPatients with cancer often experience changes in function during and after treatment but it is not clear what cancer types, and associated clinical factors, affect function. This study evaluated patient-reported functional impairments between specific cancer types and risk factors related to disease status and non-cancer factors. A cross-sectional study evaluating 332 individuals referred to cancer rehabilitation clinics was performed at six U.S. hospitals. The PROMIS Cancer Function Brief 3D Profile was used to assess functional outcomes across the domains of physical function, fatigue, and social participation. Multivariable modeling showed an interaction between cancer type and cancer status on the physical function and social participation scales. Subset analyses in the active cancer group showed an effect by cancer type for physical function (p< 0.001) and social participation (p= 0.008), but no effect was found within the non-active cancer subset analyses. Brain, sarcoma, prostate, and lymphoma were the cancers associated with lower function when disease was active. Premorbid neurologic or musculoskeletal impairments were found to be predictors of lower physical function and social participation in those with non-active cancer; cancer type did not predict low function in patients with no evidence of disease. There was no differential effect of cancer type on fatigue, but increased fatigue was significantly associated with lower age (0.027), increased body mass index (p< 0.001), premorbid musculoskeletal impairment (p< 0.015), and active cancer status (p< 0.001). Anticipatory guidance and education on the common impairments observed with specific cancer types and during specific stages of cancer care may help improve/support patients and their caregivers as they receive impairment-driven cancer rehabilitation care.