72 A major international clinical trial led by Mayo Clinic has shown promising results for patients with high-risk bladder cancer that returns after standard treatment, potentially reducing the need for bladder-removal surgery. The phase 3 study, published in The Lancet Oncology, tested an investigational oncolytic immunotherapy called cretostimogene grenadenorepvec in patients whose high-risk bladder cancer had returned despite standard treatment with Bacillus Calmette–Guérin (BCG). For these patients, bladder-removal surgery is typically the recommended next step. The therapy is delivered directly into the bladder and works by targeting cancer cells while stimulating the immune response. The treatment produced a complete response, with no detectable signs of cancer, in 75% of patients, and many of those responses lasted beyond two years. Among patients whose cancer completely disappeared after treatment, about 60% remained cancer-free two years later. In one patient, the cancer had not returned more than four years after completing treatment. Two years after starting treatment, an estimated 81% of patients had not needed bladder-removal surgery. Most treatment-related side effects were mild, temporary bladder symptoms, such as urgency or discomfort, and researchers reported no severe treatment-related side effects. The study included 115 patients treated at 41 medical centres across North America, Asia, and Australia. It was funded by CG Oncology. “Until now, patients whose cancer returned after BCG therapy have had few effective options besides bladder removal,” said Mark Tyson II, MD, lead author of the study and a urologist at Mayo Clinic in Arizona. “This study shows we may be able to offer many of those patients another option without compromising cancer control.” “For patients, this isn’t just about treating cancer; it’s about preserving quality of life,” Dr Tyson said. “Avoiding bladder removal can have a profound impact on daily living. Seeing patients remain cancer-free for years while keeping their bladder is exactly the outcome we’ve been hoping to achieve.” Bladder cancer affects thousands of people in the UK each year, with non-muscle-invasive forms representing a significant proportion of cases. Standard BCG therapy is effective for many patients but fails in a subset of high-risk cases, leaving radical cystectomy, the removal of the bladder, as a common recommendation. This surgery, while life-saving, carries substantial impacts on quality of life, including changes to urinary function and body image. The researchers concluded that cretostimogene grenadenorepvec could become an important bladder-sparing treatment option for patients whose high-risk bladder cancer has returned after standard BCG therapy. However, they noted that the treatment has not been directly compared with other bladder-sparing therapies in clinical trials and that it remains investigational. Experts say that while the results are encouraging, individual patient suitability will depend on specific disease characteristics and overall health, and discussions with specialist care teams will remain essential. The international scope of the trial, spanning multiple centres and regions, strengthens the applicability of the findings across diverse patient populations.