The RAIDER trial, a large phase II study conducted across the UK and Australia, has demonstrated the safety and feasibility of adaptive radiotherapy for bladder cancer, paving the way for potential dose escalation and improved outcomes. The trial, which involved 345 patients from 46 centers, compared standard whole-bladder treatment with two adaptive approaches: standard-dose tumor-directed therapy and dose-escalated tumor-directed therapy (DART). The primary endpoint was the proportion of patients experiencing grade 3 toxicity.
Adaptive Radiotherapy Design
The adaptive radiotherapy approach involved creating multiple treatment plans for each patient, including small, medium, and large plans based on varying margins around the tumor volume. Before each treatment, a cone beam CT scan was performed to select the optimal plan for that day, allowing for real-time adjustments based on tumor and organ movement. This approach was implemented in over 35 centers, with extensive training provided to radiographers and technicians.
Key Findings: Safety and Efficacy
The results of the RAIDER trial showed very low rates of radiotherapy-related grade 3 toxicity. Specifically, only one patient in the dose-escalated arm experienced grade 3 toxicity. This indicates that dose escalation using adaptive techniques is safe and feasible. Furthermore, the study found that most patients benefited from using multiple treatment plans throughout their course, with over 70% of patients utilizing all three plans.
While the study was not designed to directly compare outcomes between the arms, there was a trend towards improved bladder-intact event-free survival in the DART arm. The hazard ratio in favor of the DART arm was 0.81, with 71.7% at two years in the DART arm and 66.3% in the standard dose arms. Importantly, only 4% of patients required a cystectomy during the study period.
Quality of Life and Implementation
Patients tolerated the treatment well, with health-related quality of life remaining stable across all treatment arms. There was no evidence that the dose-escalated arm had worse quality of life. However, the investigators noted the importance of quality assurance and training for radiotherapy technicians to ensure optimal plan selection and treatment delivery.
Implications and Future Directions
According to Professor Robert Huddart, Chief Investigator of the RAIDER trial, the results suggest that adaptive radiotherapy can optimize target coverage and minimize normal tissue radiation in bladder radiotherapy. While further research is needed to confirm the benefits of dose escalation, the RAIDER trial provides a strong foundation for implementing adaptive techniques in clinical practice. Huddart also mentioned that they have started doing some more work using real-time adaptive therapy.
The trial also addressed the question of whole bladder versus whole pelvis radiotherapy. The investigators found that the number of patients relapsing with nodal-only relapses was low (about 7% or 8%), suggesting that bladder-only treatment may be sufficient in many cases. However, they acknowledge that further research is needed to fully address this issue.
Challenges and Considerations
The RAIDER trial highlights the importance of quality assurance in complex radiotherapy interventions. The investigators found that retraining of radiographers was necessary to improve concordance rates in plan selection. Additionally, logistical challenges related to fiducial marker placement were encountered, with only a small number of patients utilizing them in the study.
