Study: RT viable alternative to cystectomy

Standard and reduced high-dose volume radiation therapy for muscle-invasive bladder cancer provide similar tumor control and decreased late toxicity when compared to surgery, say the authors of a study from the United Kingdom.

The phase III randomized trial, which was published in the International Journal of Radiation Oncology*Biology*Physics (2013; 87:261-9), included 219 patients from 28 centers across the UK who received either standard radiation therapy or reduced high-volume radiation therapy. Patients were all 18 years of age and older and had stage T2–T4a bladder cancer. They were randomized to receive standard whole bladder radiation therapy (sRT, 108 patients) or reduced high-dose volume radiation therapy (RHDVRT, 111 patients), 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 RT 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 sRT group, the planning target volume (PTV) was the outer bladder wall, plus the extravesical extent of the tumor with a 1.5-cm margin. For patients in the RHDVRT group, two PTVs were defined: PTV1, as in the sRT 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 after treatment, 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 post treatment.

In this radiation therapy volume comparison of the study, the primary endpoints 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 post treatment. The Radiation Therapy Oncology Group (RTOG) scale and Late Effects of Normal Tissue (Subjective, Objective, Management) or LENT/SOM scale were utilized to measure late toxicity in study participants.

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 sRT and RHDVRT groups. The overall cumulative Grades 3/4 RTOG toxicity rate was 13% at 2 years following treatment, and the percentage of patients with Grades 3/4 toxicity at any specific point was shown to be <8% throughout in both groups.

Two-year locoregional recurrence-free rate was 61% for the sRT group and 64% for the RHDVRT group, but non-inferiority of locoregional control could not be formally determined in the study.

“We have now demonstrated that delivering at least 75% of the dose [of RT] to the uninvolved bladder is deliverable across multiple sites without obvious detriment to local disease control or survival, although non-inferiority could not be formally confirmed,” said lead author Robert A. Huddart, PhD, of the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London. “These results confirm, however, that RT 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.”

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