Treatment of Earlier-Stage Disease May Strengthen NMIBC-Related Survival

Thinking carefully about who may be cured from surgery alone and who may require immune checkpoint inhibitor (ICI)–based therapy may spare select patients with Bacillus Calmette-Guérin (BCG)-naïve non–muscle invasive bladder cancer (NMIBC) from overtreatment, according to Thomas Powles, MBBS, MCRP, MD.

Powles, professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London, spoke with CancerNetwork® about which data he believes will be necessary to establish the clinical utility of sasanlimab plus BCG in BCG-naïve patients with high-risk NMIBC. He spoke in the context of his presentation of a subgroup analysis of the phase 3 CREST trial (NCT04165317)evaluating the combination in this populationat the2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Powles initially described the “journey” for immune checkpoint inhibition, referencing data from studies evaluating tislelizumab (Tevimbra) and pembrolizumab (Keytruda) in patients with heavily pretreated, late-stage disease. He suggested that they did not elicit effective disease control or inhibit recurrence. He further explained that a shifting emphasis on earlier stages of muscle-invasive disease and non–muscle-invasive disease has been associated with greater event-free survival outcomes.

Highlighting dangers affiliated with both types of bladder cancer, he suggested that some patients may be cured by surgery alone, preventing the need to undergo immune checkpoint inhibitor therapy. He concluded by expressing that some patients may experience recurrence following initial treatment, and that better identifying these patients may help to better inform effective treatment for this at-risk group.

Transcript

The immune checkpoint inhibition journey has been a 10- to 12-year journey since the first tislelizumab and pembrolizumab data came out in heavily pretreated patients late in the disease. The drugs are not great at [exhibiting] fabulous control, and many patients progressed through. We showed that immune checkpoint inhibition struggled sometimes in aggressive disease, which had spread to many sites. As we’ve moved earlier into muscle-invasive disease, and now non–muscle-invasive disease, we’re seeing some quite clean, event-free survival signals. That’s underlying that biology of earlier disease from an efficacy perspective [and] is probably more attractive.

One of the dangers, of course, of muscle-invasive and non–muscle-invasive bladder cancer is many patients can be cured by surgery alone, and so there may be a degree of overtreatment. We need to think carefully about that balance. It’s also fair to say that there are [patients with] urothelial cancer who do come into harm’s way, even in non–muscle-invasive disease, with either local or metastatic [recurrence], and preventing that is important. [Sasanlimab plus BCG] will be an attractive option for some of those patients. I’d like to identify those patients better, and we’re going to try and do that. But CIS doesn’t seem to be the whole answer that question.

Reference

Powles TB, Shore ND, Bedke J, et al. Sasanlimab in combination with bacillus Calmette-Guérin (BCG) in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): Event-free survival (EFS) subgroup analyses based on disease stage from the CREST study. J Clin Oncol. 2025;43(suppl 17):4517. doi:10.1200/JCO.2025.43.16_suppl.4517