Association between PhenoAge-assessed biological age and survival outcomes in solid tumor patients treated with immune checkpoint inhibitors

Abstract Background Chronological age may influence immune function, but individuals of the same age may differ in biological aging. We evaluated the association between biological age and clinical outcomes in patients with solid tumors treated with immune checkpoint inhibitor monotherapy. Methods This retrospective two-center study included 302 patients with advanced solid tumors receiving ICI monotherapy. Biological age was estimated using the Levine PhenoAge model. Age-adjusted biological aging (PhenoAgeAccel) was defined as the residual from regression of PhenoAge on chronological age. Survival outcomes were compared according to PhenoAgeAccel status. Results The median age was 67 years; most patients had non–small cell lung cancer (78.5%) or renal cell carcinoma (18.5%). Median progression-free survival was 3.8 months (95% CI, 3.1–4.5) in patients with PhenoAgeAccel > 0, versus 7.7 months (95% CI, 5.6–9.7) in those with PhenoAgeAccel ≤ 0 ( p < 0.001). Median overall survival was 7.1 months (95% CI, 5.5–8.8) in patients with PhenoAgeAccel > 0, versus 20.4 months (95% CI, 15.1–25.8) in those with PhenoAgeAccel ≤ 0 ( p < 0.001). In multivariate analyses, PhenoAgeAccel remained an independent predictor of overall survival (HR = 2.19, 95% CI: 1.65–2.91; p < 0.001) and progression-free survival (HR = 1.93, 95% CI: 1.47–2.54; p < 0.001). Conclusion Biological age was strongly associated with survival outcomes in patients receiving immune checkpoint inhibitor monotherapy. These findings require validation in prospective cohorts and may support the integration of biological age as a prognostic biomarker in future immunotherapy trials.