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Life sciences · Journal article
BMC Cancer · October 2, 2026
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The phenomenon of Bacillus Calmette–Guérin (BCG) unresponsiveness in high-risk non-muscle invasive bladder cancer presents an unresolved clinical issue, necessitating the early identification of individuals prone to BCG resistance. Although current clinicopathological features serve as the primary indicators for recurrence and progression, the urgent requirement for novel predictive markers for BCG response is evident. A retrospective cohort of 80 patients treated with BCG was analyzed. Immunohistochemical staining was performed on tumor tissues before instillation to assess tumor immune microenvironment markers. Univariate Cox regression and Lasso analysis were conducted to identify immune-related markers with prognostic significance. These markers were then integrated with clinicopathological features to construct a model for predicting recurrence after BCG instillation, aiming to evaluate its predictive value for recurrence after BCG instillation in patients with non-muscle invasive bladder cancer. The total CD4 + cell density (CD4) and stromal CD68 + cell density (CD68s) were identified as independent prognostic markers. A combined Riskscore based on CD4 and CD68s demonstrated better predictive accuracy and discriminatory power compared to either marker alone. Furthermore, a nomogram integrating the Riskscore with clinicopathological features showed slightly improved predictive performance and net clinical benefit compared to the risk stratification models of the European Organization for Research and Treatment of Cancer (EORTC), Club Urologico Español de Tratamiento Oncológico (CUETO), and European Association of Urology (EAU). Our investigation revealed that combination immune microenvironment markers with clinical parameters can refine the risk prediction model. The new model for predicting recurrence after BCG instillation may help identify which patients will benefit from BCG bladder instillation.