Frailty and pre-frailty as independent predictors of mortality in skin cancer survivors: Findings from the US National Health Interview Survey, 1997–2018

Frailty is a multidimensional geriatric syndrome associated with adverse outcomes in aging populations and cancer patients. Although skin cancer is the most common malignancy in the United States, the prognostic role of frailty among skin cancer survivors remains unclear. This study aimed to examine whether frailty and pre-frailty are independently associated with all-cause mortality among skin cancer survivors. We analyzed data from the National Health Interview Survey 1997-2018, linked with the National Death Index through 2019. Frailty was assessed using a modified Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale, classifying participants as robust (score 0), pre-frail (1-2), or frail (3-5). The analytic sample included 14,411 adults with self-reported skin cancer. The Kaplan-Meier methods were used to estimate survival across frailty categories, and Cox proportional hazards models quantified the association between frailty and all-cause mortality, adjusting for demographic, socioeconomic, and clinical covariates. Subgroup analyses were conducted by age and sex. Among skin cancer survivors, 79.9% were robust, 10.8% were pre-frail, and 9.3% were frail at baseline. During follow-up, 1998 deaths were recorded. Frailty status was strongly associated with mortality in a dose-response manner. In the fully adjusted model, pre-frail survivors had a 38% higher risk of death (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.32-1.45; P < .001), and frail survivors had a 65% higher risk (HR, 1.65; 95% CI, 1.45-1.89; P < .001) compared with robust survivors. Among those aged ≥60 years, both pre-frailty (HR, 1.42; 95% CI, 1.36-1.50) and frailty (HR, 1.62; 95% CI, 1.40-1.88) significantly predicted mortality. In survivors younger than 60 years, frailty more than doubled the mortality risk (HR, 2.20; 95% CI, 1.38-3.50), whereas pre-frailty was not significantly associated with outcomes. Sex-stratified analyses showed consistent associations in women, while estimates in men were less precise due to smaller numbers. Frailty, as assessed by the FRAIL scale, is an independent predictor of all-cause mortality among skin cancer survivors. Incorporating frailty screening into survivorship care may enable early identification of high-risk individuals and inform tailored interventions to improve long-term outcomes.