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<p><b>OBJECTIVE: </b>We aim to assess the prevalence and associated factors of clinical depression in older patients with cancer.</p><p><b>METHODS: </b>We studied a prospective cohort of cancer patients aged ≥ 70 years and referred to geriatric oncology clinics between 2007 and 2012. A multidimensional geriatric assessment was performed before choosing the cancer-treatment strategy. Clinical depression was diagnosed by senior geriatricians by a semi-structured interview. It encompassed criteria of the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) and of the International Classification of Diseases (10th edition). Multivariate logistic regression was performed.</p><p><b>RESULTS: </b>Of 1121 consecutive patients, 1092 had available data (mean age, 80.4 years; women, 48.8%; metastases, 51.3%; cancer location: colorectal 21.1%, breast 16.8%, kidney, bladder or urinary tract 14.0%, and prostate 11.4%). The overall prevalence of clinical depression was 28.4% (95% confidence interval, 25.7-31.2). Factors independently associated with clinical depression by multivariate analysis adjusting for all following factors plus gender, and metastasis were impaired mobility (adjusted odds ratio [aOR], 2.35; 1.59-3.46), impaired functional status defined as Eastern Cooperative Oncology Group Performance Status ≥ 2 (aOR, 2.39; 1.66-3.43) or as activities of daily living < 6 (aOR, 2.43; 1.73-3.41), inpatient status (aOR, 1.68; 1.20-2.37), inadequate social support (aOR, 1.66; 1.16-2.37), cognitive impairment (aOR, 1.76; 1.24-2.49), polypharmacy defined as five or more non-antidepressant drugs (aOR, 1.65; 1.14-2.38), multimorbidity (aOR additional CIRS-G point , 1.08; 1.04-1.12), and cancer-related pain (aOR, 1.76; 1.26-2.46).</p><p><b>CONCLUSION: </b>In older patients with as-yet untreated cancer at various sites and stages, clinical depression was highly prevalent. Clinical depression was independently associated with several geriatric assessment findings (impaired mobility and function, inadequate social support, cognitive impairment, polypharmacy, and multimorbidity) independently from gender, tumor site, and metastatic status.</p>