Standard and Reduced High-Dose Volume Radiation Therapy for Muscle-Invasive Bladder Cancer Have Comparable Tumor Control
Standard and reduced high-dose volume radiation therapy for muscle-invasive bladder cancer provide comparable tumor control and decreased late toxicity when compared to surgery, according to a study published in the October issue of the International Journal of Radiation Oncology • Biology • Physics. The research is part of the BC2001 clinical trial, the largest randomized trial of radiation therapy in patients with muscle-invasive bladder cancer.
Cystectomy is often the standard treatment for patients with muscle-invasive bladder cancer; however, advanced radiation therapy techniques that spare the bladder may be an effective alternative for patients who are unsuitable for or unwilling to undergo cystectomy. This research was conducted to determine whether some of the drawbacks of radiation therapy of the bladder, such as local recurrence and late toxicity risks, could be reduced with a lower dose of radiation being delivered to the areas of the bladder outside of the tumor region, and to assess the tumor control and toxicity of radiation therapy.
Phase III Trial
The cohort of participants for this portion of the phase III randomized trial included 219 patients from 28 centers across the United Kingdom who received either standard radiation therapy or reduced high-volume radiation therapy. Patients were all age 18 and older and had stage T2 to T4a bladder cancer. Study participants were randomly assigned to receive standard whole-bladder radiation therapy (n = 108) and reduced high-dose volume radiation therapy (n = 111), in which the full radiation dose was delivered to the tumor and 80% of the maximum dose was delivered to the uninvolved bladder.
Study participants received radiation therapy doses based on their cancer center’s choice of either 55 Gy/20 fractions over 4 weeks or 64 Gy/32 fractions over 6.5 weeks. For patients in the standard whole-bladder radiation therapy group, the planning target volume was the outer bladder wall, plus the extravesical extent of the tumor with a 1.5-cm margin. For patients in the reduced high-dose volume radiation therapy group, two planning target volumes (PTV) were defined: PTV1, as in the standard whole-bladder radiation group, and PTV2, as the gross tumor volume plus a 1.5-cm margin.
Patients were assessed weekly throughout treatment for toxicity; and side effects were measured at 6, 9, and 12 months posttreatment, and annually thereafter. Additionally, tumor control was assessed at 6, 9, and 12 months after treatment and then annually for up to 5 years. The median patient follow-up time was 72.7 months posttreatment.
In this radiation therapy volume comparison of the study, the primary endpoints of interest were late toxicity and local control. Late toxicity was determined in this study to be radiation therapy-related side effects at least 1 to 2 years posttreatment. The Radiation Therapy Oncology Group (RTOG) scale and Late Effects of Normal Tissue (Subjective, Objective, Management) (LENT/SOM) scale were utilized to measure late toxicity in study participants.
Outcomes
Two-year locoregional recurrence–free rate was 61% for the standard whole-bladder radiation therapy group and 64% for the reduced high-dose volume radiation therapy group, but noninferiority of locoregional control could not be formally determined in the study.
Rates of late toxicity were lower than anticipated, and the number of patients reporting RTOG or LENT/SOM toxicities was not significantly different between the standard whole-bladder radiation therapy and reduced high-dose volume radiation therapy groups. The overall cumulative grades 3/4 RTOG toxicity rate was 13% at 2 years posttreatment, and the percentage of patients with grades 3/4 toxicity at any specific point was shown to be < 8% throughout in both groups.
“We have now demonstrated that delivering at least 75% of the dose [of radiation therapy] to the uninvolved bladder is deliverable across multiple sites without obvious detriment to local disease control or survival, although noninferiority could not be formally confirmed,” said lead author Robert A. Huddart, PhD, of The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. “These results confirm, however, that radiation therapy is an effective alternative for patients unable to undergo cystectomy. Further study using image-guided treatment with or without dose escalation is now also warranted.”
The study was sponsored by the University of Birmingham, UK, supported by Cancer Research UK, and facilitated by the National Institute for Health Research Cancer Research Network.
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