Bladder preservation with trimodality therapy may be a safe and effective alternative to cystectomy for selected patients with muscle-invasive bladder cancer, according to results from a phase II trial presented by Coen et al at the virtual 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 55).
NRG-RTOG 0712
The phase II NRG Oncology NRG-RTOG 0712 trial evaluated two regimens: one was a regimen of flourouracil (5-FU) and cisplatin with twice-daily radiation, and the other was a regimen of gemcitabine and daily radiation that had demonstrated efficacy in single-institution clinical trials. This trial sought to determine if either or both of these regimens demonstrated sufficient efficacy to be included in future larger studies. The previously published results demonstrated high efficacy rates and low rates of distant metastasis in both arms.
NRG-RTOG 0712 accrued 66 eligible patients with muscle-invasive bladder cancer for analysis, and randomly assigned them to the 5-FU/cisplatin and twice-daily radiation or gemcitabine and once-daily radiation regimens. The trial was designed to determine if either or both treatments exceed a 3-year distant metastasis–free rate of 75% defined as the benchmark for efficacy. Researchers on the trial also assessed 5-year distant metastasis–free rates, toxicity, complete response, and bladder-intact distant metastasis–free survival for each treatment arm. This trial was not statistically powered to compare the two treatment regimens.
Results
With a median follow-up of 7.3 years, the 5-FU/cisplatin and twice-daily radiation treatment arm yielded a 79% 3-year distant metastasis–free rate, and the gemcitabine and once-daily radiation treatment arm had a 3-year distant metastasis–free rate of 85%. Secondary objectives and efficiency endpoints data demonstrated that:
- 5-year distant metastasis–free rates were 70% in the 5-FU/cisplatin and twice-daily radiation treatment arm and 77% in the gemcitabine and once-daily radiation treatment arm.
- 3-year bladder-intact distant metastasis–free survival rates were 67% for the 5-FU/cisplatin and twice-daily radiation treatment arm and 72.5% for the gemcitabine and once-daily radiation treatment arm; 5-year rates were 65.1% and 72.5%, respectively.
- Postinduction complete response rates were 88% for the 5-FU/cisplatin and twice-daily radiation arm and 76% for the gemcitabine and once-daily radiation arm.
Fifty-eight percent of patients in the 5-FU/cisplatin and twice-daily radiation treatment arm had treatment related-grade 3 or 4 hematologic, gastrointestinal, or genitourinary toxicities; 52% of patients in the gemcitabine and once-daily radiation arm exhibited these toxicities. Both regimens demonstrated a 3-year distant metastasis–free rate greater than 75%, thus confirming gemcitabine and daily radiation is an acceptable alternative treatment option.
"Not only did this trial conclude that gemcitabine and daily radiation is an acceptable regimen with favorable distant metastasis–free rates at 3 years, the results also indicate that both treatments maintain their high distant metastasis–free [rates] at 5 years and both treatments had low cystectomy rates with high overall survival rates. The efficacy of the gemcitabine and once-daily radiation regimen may facilitate wider adoption of bladder preservation as many patients have comorbidities that preclude the use of cisplatin."— John J. Coen, MD
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“Not only did this trial conclude that gemcitabine and daily radiation is an acceptable regimen with favorable distant metastasis–free rates at 3 years, the results also indicate that both treatments maintain their high distant metastasis–free [rates] at 5 years and both treatments had low cystectomy rates with high overall survival rates. The efficacy of the gemcitabine and once-daily radiation regimen may facilitate wider adoption of bladder preservation as many patients have comorbidities that preclude the use of cisplatin. The daily radiation schedule is also easier for patients and treatment centers to administer than twice-daily treatment, which will also likely increase interest in this strategy. These findings are important to future trials that may assess a systemic therapy for this muscle-invasive bladder cancer,” stated John J. Coen, MD, of 21st Century Oncology and principal investigator of the NRG-RTOG 0712 study.
Disclosure: For full disclosures of the study authors, visit myastroapp2020.com.
