Associations of Pre-Diagnostic Cardiorespiratory Fitness and Handgrip Strength With All-Cause Mortality and 15-Year Survival After Cancer Diagnosis

Objective To determine the prospective dose-response associations of pre-diagnostic estimated CRF and handgrip strength with all-cause mortality and 15-year survival probability.Patients and methods Prospective cohort study using UK Biobank data from cancer-free participants who completed submaximal cycle ergometry and handgrip dynamometry at baseline (2006-2010) and were subsequently diagnosed with cancer (ICD-10 C00-C97). All-cause mortality was modelled using Royston-Parmar flexible parametric models with restricted cubic splines. Fifteen-year post-diagnosis survival probabilities were estimated from Poisson regression.Results Among 10,462 participants (mean age 60.0 years, 55% men, median follow-up 12.5 years), 2,101 deaths occurred. Estimated CRF showed a curvilinear inverse association with mortality: relative to the median (27.9 ml·kg-1·min-1), a VO2max of 12.5 ml·kg-1·min-1 was associated with 59% higher mortality (HR 1.59;95% CI 1.28-1.98), with risk declining continuously without plateau (HR 0.71;0.56-0.89 at 44.5 ml·kg-1·min-1). Handgrip strength showed a weaker, curvilinear inverse association that plateaued at the median (32 kg): at 12 kg, mortality was 37% higher (HR 1.37;1.11-1.67), with no further reduction beyond the reference. Fifteen-year survival rose linearly from 39.3% to 77.4% across the estimated CRF range versus 49.8% to 71.7% for handgrip strength.Conclusion Among participants who later developed cancer, estimated CRF showed a stronger association with mortality than handgrip strength in this cohort. These findings highlight the importance of pre-diagnostic lifestyle interventions to improve long-term survival, though both fitness components may contribute through distinct physiological pathways.