Study identifies patients with NMIBC who are unlikely to respond to BCG therapy

Investigators from Cedars Sinai Cancer found that BCG Response Subtype 3 (BRS3)—a subtype of bladder cancer tumor—was associated with reduced progression-free survival (PFS) in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) following treatment with intravesical BCG therapy compared with other subtypes.^1,2

“These findings provide a potential tool for determining how well patients initially treated for high-risk bladder cancer that isn’t yet muscle invasive will respond to the most common follow-up therapy," says Dan Theodorescu, MD, PhD.

The data were presented in Science Translational Medicine.

“These findings provide a potential tool for determining how well patients initially treated for high-risk bladder cancer that isn’t yet muscle invasive will respond to the most common follow-up therapy. With this information, clinicians can make more informed and timely decisions about aggressive surgical treatment or take advantage of new options being created through precision medicine,” said senior author Dan Theodorescu, MD, PhD, in a news release on the findings.² Theodorescu is the director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair.

The study included 132 patients with high-risk NMIBC who had never received BCG therapy and 44 who experienced recurrence following treatment with BCG therapy. Among these patients, 3 subtypes of bladder cancer tumors (BRS1, BRS2, and BRS3) were identified for comparative analysis.

The investigators found that patients who experienced recurrence following BCG therapy were more likely to have BRS3 tumors compared with BRS1 or BRS2. The BRS3 subtype was also associated with a reduced PFS compared with the other 2 subtypes, with a 2-year PFS of 61%, compared with 78% for BRS2 and 83% for BRS1. Upon multivariate analysis, BRS3 compared with BRS1 and BRS2 was shown to be an independent predictor of PFS (P < .001).

“Patients who don’t respond have been exposed to unnecessary toxicity from BCG treatment and, because of the delay in receiving more aggressive treatment, their chances of survival may have been compromised. Our goal with this study was to find a new way to identify these patients before they receive BCG therapy and direct them immediately to surgical removal of the bladder or other more aggressive therapies, which may reduce quality of life but have excellent long-term outcomes,” explained Theodorescu in the news release.

As a way to identify patients who won’t respond to BCG therapy before they receive treatment, the investigators tested a quantitative polymerase chain reaction-based assay and found that the test could accurately identify patients who had BRS3 high-risk NMIBC. The model had a sensitivity of 78% and a specificity of 86%.

A further study, called IMPASSE, has been initiated to validate the study’s findings over time.

“The aim of this new trial is to further determine whether BRS3 can help us predict patients’ response to treatment. We believe that this marker can also help us investigate alternatives to BCG treatment and ultimately improve outcomes and survival rates for non-muscle invasive bladder cancer patients,” said Theodorescu.

References

1. De Jong FC, Laajala TD, Hoedemaeker RF, et al. Non–muscle-invasive bladder cancer molecular sub-types predict differential response to intravesical Bacillus Calmette-Guérin. Sci Transl Med. Published May 24, 2023. Accessed May 30, 2023. doi:10.1126/scitranslmed.abn4118.

2. New bladder cancer classification predicts treatment response. News release. Cedars-Sinai Cancer. May 24, 2023. Accessed May 30, 2023. https://www.newswise.com/articles/new-bladder-cancer-classification-predicts-treatment-response?sc=mwhr&xy=10016681