Beyond chemobrain: A stepwise approach to identifying cognitive impairment in non-CNS cancer survivors

Cancer-related cognitive impairment (CRCI) is common in patients with non-central nervous system malignancies, but its identification remains difficult because symptoms are heterogeneous, may predate treatment, and are not captured by a single measure. This narrative review synthesizes evidence on epidemiology, clinical phenotype, risk factors, neuropsychological assessment, neuroimaging, and practical pathways for identifying CRCI in oncology care. Emerging literature highlights subjective-objective discordance and self-awareness as clinically relevant dimensions. Prevalence varies by timing and method, with higher estimates from self-report than from screening tools or formal batteries. Identification is more reliable when assessment combines patient-reported outcomes (PRO), brief objective screening, and focused neuropsychological testing within baseline vulnerability and concurrent symptom burden. Older age, lower cognitive reserve, pretreatment cognitive impairment, systemic illness, fatigue, insomnia, mood symptoms, pain, and medication effects are major modifiers. In clinical settings, neuroimaging is useful primarily for differential diagnosis: conventional brain MRI excludes competing neurologic disorders, while volumetric MRI, diffusion imaging, resting-state functional MRI, and [18F]FDG-PET currently provide group-level evidence rather than individual diagnostic signatures. At present, CRCI is best identified through a stepwise clinical strategy integrating PRO evaluation, objective testing, risk profiling, and selective imaging, considering individual patient modifiers rather than a single diagnostic test.