September 06 2024
Recent results from the single-arm, Phase II NRG Oncology RTOG 0926 (NRG-RTOG 0926) trial assessing trimodality therapy as an alternative to radical cystectomy suggest that trimodality therapy is a possible alternative treatment for patients with recurrent, high-grade T1 urothelial cancer of the bladder. NRG-RTOG 0926 results show that, of the patients treated with radiotherapy combined with radiosensitizing chemotherapy after transurethral resection (trimodality therapy) on the trial, 88% of patients remained free of cystectomy at 3 years following treatment. The results were recently published in the Journal of Clinical Oncology.
Although standard of care treatment for patients with this type of bladder cancer is intravesical therapy, cystectomy remains a widely accepted treatment alternative. Intravesical therapy is often successful in this patient population, but if the patient recurs following this treatment, they are typically recommended to receive a radical cystectomy. NRG-RTOG 0926 was developed as a way to explore bladder-sparing treatment in these patients. Prior research has shown successful outcomes with the use of bladder-sparing treatments in muscle-invasive cancer and trimodality approaches have been shown to be efficacious in higher-stage disease, but this had not yet been evaluated in a cooperative group trial for patients with T1 disease who were recommended to undergo cystectomy.
The primary objective for NRG-RTOG 0926 was to determine 3-year freedom from cystectomy for patients. Secondary endpoints included distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival, and safety.
Efficacy and safety were evaluated in 34 patients on NRG-RTOG 0926. The median follow up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit (CI): 72%) which met the primary study goal. Overall survival at 3 and 5 years was 69% (95% CI: 54–85%) and 56% (95% CI: 39–74%). The distant metastasis rates at 3 and 5 years were 12% (95% CI: 4–26%) and 19% (95% CI: 7–34%). Eight patients died of urothelial cancer, 12 exhibited local recurrence within 3 years (cumulative incidence: 32%; 95% CI: 17–48%). Eighteen patients experienced grade 3 adverse events and 1 patient developed grade 4 neutropenia.
“While NRG-RTOG 0926 successfully provided a potential alternative to radical cystectomy, there remains an urgent need to find an improved systemic therapy for these patients as the frequency of local recurrence and the rate of distant metastases and fatal carcinoma are a concern. There are studies in progress or development surveying immunotherapy with chemoradiotherapy in this disease for both muscle-invasive disease and high-grade T1 bladder cancer” stated Douglas M. Dahl, MD of the Massachusetts General Hospital, Harvard Medical School, and the Lead Author of the NRG-RTOG 0926 manuscript.
This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), and U24CA180803 (IROC) from the National Cancer Institute (NCI), part of the National Institutes of Health.
Citation
Dahl DM, Rodgers JP, Shipley WU, Michaelson MD, Wu CL, Parker W, Jani AB, Cury FL, Hudes RS, Michalski JM, Hartford AC, Song D, Citrin DE, Karrison TG, Sandler HM, Feng FY, Efstathiou JA. Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024 Sep 3:JCO2302510. doi: 10.1200/JCO.23.02510. Epub ahead of print. PMID: 39226514.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.