Optimizing Surveillance and Counseling for BCG-Unresponsive Bladder Cancer

The recent FDA approval of the gemcitabine intravesical system (Inlexzo), formerly TAR-200, marked a pivotal moment in the treatment of Bacillus Calmette-Guérin (BCG)–unresponsive, non-muscle-invasive bladder cancer (NMIBC). The product’s prescribing information includes a crucial warning about the risk of metastatic bladder cancer with a delayed radical cystectomy, a risk that clinicians must address directly with their patients. Gary Steinberg, MD, a professor in the Department of Urology at Rush University, provided insight on how to effectively counsel patients and implement a robust surveillance strategy.

Steinberg explained that while a delay in cystectomy carries a risk, newer data from trials like the phase 2 SunRISe-1 study (NCT04640623) showed a complete response rate of 82% (95% CI, 72%-90%). At 1 year, 51% of patients maintained a response.

Steinberg emphasized that patient counseling must be paired with a surveillance protocol. He outlined the importance of regular cystoscopies, urinary cytologies, and advanced imaging such as CT or MRI scans as needed. He noted that the evolving landscape of bladder-preserving therapies means that patients can now try multiple different agents with varying mechanisms of action.

Transcript:

When you look at the older data vs the newer data, the risk of progression is not as high as we once thought. As we see in the [gemcitabine intravesical system] data, 8% of their patients progressed to muscle-invasive disease within 12 months. We do need to be very careful and make sure that we follow up with patients with cystoscopies, urinary cytologies, CT [scans], or MRI imaging as needed. We do have room to try 1, if not 2, and even potentially 3 additional therapies once patients become BCG unresponsive. We saw in the trial that led to the pembrolizumab [Keytruda] approval in BCG-unresponsive carcinoma in situ, the KEYNOTE-057 trial [NCT02625961], that there were a fair number of patients who did not respond to pembrolizumab, who did not undergo cystectomy, and were followed with multiple different other therapies, and that the progression rate was still very low.

I was one of the co-authors of a retrospective review. We took retrospective data from 10 different medical centers on patients who were deemed BCG-unresponsive and looked at their additional treatments that they got over time. We saw that patients were able to get a second treatment. Once we start getting into the third and fourth lines of therapy after BCG, we then begin to see more progression to muscle invasion. Patients are going to want at least 1 attempt, if not 2 attempts, with different mechanisms of action once they become BCG unresponsive and still have [NMIBC].

Reference

U.S. FDA approval of INLEXZO™ (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed September 9, 2025. https://tinyurl.com/4zjz22z7