CONTEXT: More than half of new cancer cases occurred in older adults. Older patients with cancer are particularly at risk of physical, psycho-existential or socio-familial suffering as defined by the concept of Serious Health-related Suffering (SHS). OBJECTIVES: To assess the direct and indirect effects of physical, psycho-existential and socio-familial dimensions of suffering on cancer treatability, supportive care needs and 12-month mortality in older patients with cancer. METHODS: We included patients with cancer aged 70 years and over from the Elderly Cancer Patients cohort (ELCAPA, Ile-de-France), referred for geriatric assessment between 2007 and 2019 before cancer treatment. Structural equation modelling examined the direct and indirect relationships between SHS dimensions (latent variables), patients' characteristics (age, sex, tumor location and metastatic status, comorbidity, period of care), and outcomes. RESULTS: The analysis included 4,824 patients (mean age: 82.2 ± 4 years; women: 56%; main cancer sites: breast [22.3%], colorectal [15.2%], prostate [8.5%], and lung [6.8%]; metastatic cancer: 46%). Physical suffering had direct pejorative effects on cancer treatability, and mortality (standardized coefficient [SC] = 0.12 [P < 0.001], SC = 0.27 [P < 0.001], respectively). Psycho-existential and socio-familial sufferings had indirect pejorative effects on survival through decreased cancer treatability (SC = 0.08 [P < 0.001], SC = 0.03 [P < 0.001], respectively). Psycho-existential dimension had the main direct effect size on supportive care needs (SC = 0.35 [P < 0.001]) and was interrelated with physical suffering. CONCLUSION: Physical suffering has direct pejorative effect on survival. All dimensions indirectly decrease survival due to poorer cancer treatability. Our findings support concomitant management of physical and psycho-existential suffering.Read less <