ADVANCED 2 BCG Naive cohort

The BCG-naive treatment space is becoming increasingly important, especially in light of the ongoing global shortage of BCG. This shortage is affecting many providers and limiting access to a therapy that has long been the standard for non–muscle-invasive bladder cancer. While efforts are underway to improve BCG production and diversify supply through multiple strains, the current reality has created a pressing need to explore alternative therapies. BCG remains effective, affordable, and predictable, but the limitations in availability and variable patient responses highlight the need for new data and options in this setting.

BCG continues to be the benchmark therapy for BCG-naive patients, but it’s clear that not all patients are able to generate a strong immune response from it. For example, immunosuppressed individuals or those with certain tumor characteristics may not benefit as reliably from BCG. In contrast, cytotoxic treatments like gemcitabine and docetaxel may perform better in these cases. The key question is whether this specific subgroup can be identified early so their treatment can be tailored—possibly by intensifying therapy or using alternative immune-stimulating agents—to improve their outcomes. Understanding these distinctions could guide more personalized, effective care strategies.

There has been significant clinical focus on BCG-unresponsive disease over the past few years but much less on the BCG-naive population. This imbalance is beginning to shift, with a growing number of trials now evaluating immune-based intensification strategies in BCG-naive patients. These efforts reflect a broader, more aggressive approach to those who may need it most. Overall, expanding therapeutic options and generating robust data in this space are essential. Doing so not only supports patient care in the face of BCG shortages but also advances the science behind treatment selection and immune responsiveness in early-stage bladder cancer.