Editorial: Microbial biomarkers predicting BCG therapy response in non-muscle invasive bladder cancer

Intravesical Bacillus Calmette-Guérin (BCG) remains the most effective adjuvant immunotherapy for NMIBC and has been widely used for decades. 1 Despite its clinical success, however, a substantial proportion of patients fail to respond adequately to treatment or experience recurrence after therapy. To identify some reliable biomarkers capable of predicting response to BCG remains one of the most pressing challenges in the management of NMIBC. 2 In recent years, there have been an increasing attention toward the role of host immunity and microbial ecosystems in shaping responses to cancer and BC immunotherapy. 3 The human body hosts complex microbial communities that influence both innate and adaptive immune responses.Advances in sequencing technologies have revealed that the urinary tract is not sterile, as previously believed, but instead harbors a diverse microbiome that may interact with the tumor microenvironment and modulate therapeutic responses. Similarly, previous analyses have shown that elevated systemic inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with poorer outcomes in NMIBC patients undergoing intravesical BCG therapy. These findings further support the hypothesis that systemic immune status plays a critical role in determining treatment response and disease progression.Collectively, such markers represent attractive candidates for easily accessible and cost-effective predictive tools in routine clinical practice.Taken together, the studies included in this Research Topic highlight the complexity of the immune landscape in NMIBC and emphasize the multifaceted nature of BCG therapy response. While BCG has long been recognized as a potent immunotherapeutic agent, the mechanisms underlying its clinical efficacy remain incompletely understood. The interaction between tumor cells, host immune responses, and microbial communities within the urinary tract may play a crucial role in shaping treatment outcomes. The identification of reliable predictive biomarkers is particularly important given the substantial heterogeneity observed in clinical responses to BCG. Early identification of patients unlikely to benefit from BCG therapy could facilitate more timely adoption of alternative treatments, including radical cystectomy or emerging bladder-sparing strategies such as immune checkpoint inhibitors and novel intravesical therapies. 4 In addition, future investigations should place greater emphasis on the early identification of BC histological rare variants, which may underlie heterogeneous immune responses to BCG and represent overlooked determinants of treatment resistance in specific patient subsets. 5 Future research will likely benefit from integrative approaches combining microbiome profiling, immune monitoring, and molecular characterization of tumors. In addition, prospective studies incorporating longitudinal sampling of urine, blood, and tumor tissue will be essential to validate candidate biomarkers and clarify their clinical utility. In conclusion, the contributions presented in this Research Topic provide valuable insights into the immunological and biological factors associated with BCG therapy response in NMIBC. By exploring novel immune and microbial biomarkers, these studies contribute to a growing body of evidence supporting a more personalized approach to bladder cancer management. Continued investigation into the complex interplay between host immunity, microbial ecosystems, and tumor biology may ultimately lead to improved predictive tools and more effective therapeutic strategies for patients with NMIBC.