Who benefits most from adding IO to BCG in NMIBC?

In an interview discussing immunotherapy combinations with BCG for high-risk non-muscle-invasive bladder cancer (NMIBC), Bogdana Schmidt, MD, MPH, outlined which patients may derive the greatest benefit and offered a measured view of how these regimens would likely be adopted in practice.

Patient selection: Schmidt identified several subgroups most likely to harbor occult systemic disease and therefore potentially benefit from adding immunotherapy to BCG: patients with T1 disease, lymphovascular invasion (LVI), or significant concomitant carcinoma in situ (CIS). She also highlighted patients with detectable circulating tumor DNA (ctDNA), noting that a positive ctDNA result in the NMIBC setting likely signals more advanced disease than conventional staging reveals. Younger, bladder-preservation–motivated patients who are unwilling to pursue cystectomy as salvage therapy represent another group worth considering for upfront intensification. Notably, among patients with T1, CIS, and LVI, more than half fail to respond to BCG and ultimately become BCG-unresponsive, making early escalation a rational consideration.

Real-world adoption: Despite this rationale, Schmidt anticipates that immunotherapy-BCG combinations will be used selectively rather than broadly across high-risk NMIBC. A central concern is the adverse event profile of checkpoint inhibitors—particularly the potential for permanent autoimmune toxicities that, although uncommon, can be severe and lifelong. For patients whose disease might otherwise be controlled with intravesical therapy alone, that toxicity burden represents a significant trade-off. She expects both urologists and patients to weigh these risks carefully, limiting uptake to those in whom the benefit-risk calculus most clearly favors intensified treatment.