Interplay of IL‐6, GDF‐15 and Sarcopenia in Patients With Bladder Cancer Undergoing Radical Cystectomy and Its Implications on Survival

ABSTRACT Background Sarcopenia has emerged as a significant predictor of adverse outcomes in cancer. Specifically, this is also true for patients with bladder cancer undergoing radical cystectomy (RC). This retrospective study investigates the roles of the biomarkers interleukin‐6 (IL‐6) and growth differentiation factor‐15 (GDF‐15), in the context of sarcopenia, assessing their impact on oncological and survival outcomes. Methods Preoperative serum IL‐6 and GDF‐15 levels were analysed in 179 patients undergoing RC. Their association with sarcopenia, adverse pathological features and survival outcomes was investigated. Results Elevated IL‐6 and GDF‐15 levels were significantly correlated with the presence of sarcopenia ( p = 0.04 and p = 0.03, respectively). IL‐6 and GDF‐15 levels in serum showed a positive correlation (Spearman r = 0.45, 95%CI 0.32–0.56, p < 0.01). Higher IL‐6 and GDF‐15 levels were also associated with higher tumour stages (both p < 0.01), positive lymph nodes ( p = 0.02 and p < 0.01) and unfavourable surgical margins (both p < 0.01). Patients with both sarcopenia and high IL‐6 or GDF‐15 levels exhibited significantly worse overall survival and cancer‐specific survival in multivariate Cox regression analysis. Conclusions These findings highlight the interplay between IL‐6, GDF‐15, sarcopenia and tumour progression, suggesting that IL‐6 and GDF‐15 may serve as valuable prognostic biomarkers and potential therapeutic targets. Further research is warranted to explore targeted therapeutic strategies aimed at mitigating sarcopenia and systemic inflammation in this patient population.