Are Immune Checkpoint Add-Ons to BCG Worth the Risk?

The Latest on Immune Checkpoint Inhibitors in Bladder Cancer Treatment

In a significant update presented at the 2025 European Society for Medical Oncology (ESMO) annual meeting, the effectiveness of adding immune checkpoint inhibitors to the standard Bacillus Calmette-Guérin (BCG) therapy for non–muscle invasive bladder cancer (NMIBC) is under scrutiny. While there are small signs of reduced recurrences among some patients, the overall findings raise concerns about safety and the strong possibility of adverse effects.

What the Trials Showed

Three recent phase 3 trials explored the benefits of combining immune checkpoint inhibitors with BCG. The POTOMAC trial coupled BCG with durvalumab (Imfinzi), while the ALBAN trial paired it with atezolizumab (Tecentriq). A third study, CREST, tested the investigational PD-1 blocker sasanlimab alongside BCG. Only the POTOMAC trial reported significant results, showing a modest reduction in recurrences; however, both POTOMAC and ALBAN trials indicated increased rates of adverse effects that were notably severe.

Understanding the Risks

Dr. Bradley McGregor of the Dana-Farber Cancer Institute indicated that a worrying trend exists within the trials: significant toxicity correlated with the addition of immune therapy. For instance, the CREST trial documented a 29.1% occurrence of treatment-related adverse events rated 3 or higher among sasanlimab patients, versus just 6.3% in those receiving BCG alone. Similarly concerning were the results from the POTOMAC trial, where 21% of patients experienced serious adverse events related to durvalumab.

Challenges in Patient Selection

One pressing issue that emerged from these clinical trials is the challenge in identifying which patients might benefit from immune checkpoint inhibitors in combination with BCG. Currently, physicians lack a clear method to discern which patients would gain efficacy from the regimen, leaving many high-risk patients vulnerable to unnecessary side effects with minimal advantage.

Bladder Preservation: A Primary Goal

A crucial aspect of treatment for NMIBC patients is bladder preservation. Despite the trials indicating some level of reduced recurrence, they did not include cystectomy-free survival as a primary endpoint, raising doubts about whether these therapies contribute to preserving the bladder. Dr. Morgan Roupret from Sorbonne University echoed this sentiment, emphasizing that the trials primarily address the avoidance of recurrent TURBT procedures rather than preserving the bladder, which is ultimately the main concern for patients.

Next Steps and The Role of Immune Checkpoint Inhibitors

Although immune checkpoint inhibitors such as pembrolizumab and atezolizumab are promising in treating BCG-unresponsive NMIBC, the trials suggest that a reevaluation may be necessary. The current data calls for comprehensive trials that explore the long-term effectiveness of these therapies while also navigating the safety concerns presented.

Conclusion: A Deeper Look into Treatment Options

As we digest these findings, it is clear that the simple addition of immune checkpoint inhibitors to BCG therapy does not guarantee improved outcomes. Physicians, patients, and stakeholders must critically evaluate the implications of this combined approach against the backdrop of toxicity risks and blurred benefits. The true test will lie in future research that identifies effective patient selection strategies to mitigate harm and enhance the therapeutic landscape for NMIBC.