The ongoing shortage of Bacillus Calmette-Guérin (BCG) continues to significantly impact bladder cancer treatment decisions, even as new therapeutic options emerge. This challenge has become particularly relevant following the April 2024 FDA approval of nogapendekin alfa inbakicept-pmln (Anktiva) plus BCG for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC).
Treatment Adaptation Amid BCG Scarcity
Dr. Vikram M. Narayan of Emory University Hospital highlights the complex reality facing clinicians. While nogapendekin alfa inbakicept represents a significant advancement, its approval is based on clinical trials using full-dose BCG with maintenance therapy extending up to 37 months. However, many institutions, including Emory, have adopted split-dose BCG protocols due to supply constraints.
"Many practices have limited supply of full dose BCG, or in accordance with AUA and SUO guidance, do split dose treatments," explains Dr. Narayan. This situation creates challenging decisions about resource allocation and treatment prioritization between newly diagnosed patients and those with BCG-unresponsive disease.
Emerging Solutions and Alternative Approaches
Relief may be on the horizon with a new BCG manufacturing facility expected to come online within 6-12 months. The current manufacturing process, which produces BCG in two-year cycles to maintain bacterial homogeneity, contributes to periodic shortages as supply approaches cycle end.
Alternative treatment options are gaining attention, particularly nadofaragene firadenovec-vncg (Adstiladrin), which offers a more convenient quarterly dosing schedule. "Perhaps one of the best things about nadofaragene firadenovec-vncg as a treatment option is it's given via quarterly dosing," notes Dr. Narayan.
Advanced Diagnostic Tools Reshaping Care
The field is witnessing the emergence of innovative diagnostic approaches. The Vesta product from Valar Labs employs artificial intelligence to analyze pathology slides, potentially identifying patterns invisible to the human eye. Additionally, urinary cell-free DNA testing, such as the UroAmp test, shows promise in detecting minimal residual disease at the molecular level.
Treatment Selection and Sequencing Challenges
Clinicians face complex decisions regarding treatment sequencing among available options, including:
- FDA-approved agents like pembrolizumab
- Nadofaragene firadenovec
- Nogapendekin alfa inbakicept plus BCG
- Clinical trials
- Off-label gemcitabine/docetaxel combinations
The cost implications of newer treatments add another layer of complexity to treatment decisions, highlighting the need for comprehensive cost-effectiveness studies to guide therapy selection.
Future Directions
Research continues to explore combination strategies, with studies like the phase 2 ABLE-22 trial investigating nadofaragene firadenovec in combination with chemotherapy or immunotherapy. Additionally, investigations into different BCG strains, including non-US variants, may help address supply challenges if non-inferiority can be demonstrated.
As the field evolves, the importance of personalized treatment decisions based on individual patient factors, resource availability, and emerging diagnostic tools becomes increasingly apparent. The integration of new technologies and therapeutic approaches, combined with efforts to resolve BCG supply issues, suggests a gradually improving outlook for bladder cancer care.
