Reduced Radiation Dose Possible in Bladder Cancer

Megan Brooks

October 16, 2013

One of the largest randomized trials of radiation therapy (RT) in patients with muscle-invasive bladder cancer has found that standard-dose whole-bladder RT (sRT) and reduced high-dose volume RT (RHDVRT) yield comparable tumor control.

However, the investigators were unable to demonstrate the anticipated reduction in toxicity with RHDVRT.

These findings, the latest results from the British BC2001 clinical trial, were published in the October 1 issue of the International Journal of Radiation Oncology, Biology and Physics.

"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 noninferiority could not be formally confirmed," lead investigator Robert A. Huddart, PhD, from the Institute of Cancer Research in London, United Kingdom, and The Royal Marsden NHS Foundation Trust, said in a statement.

"These results confirm, however, that RT is an effective alternative for patients unable to undergo cystectomy," he added.

These results, from the radiation portion of the BC2001 trial, add to previously reported results from the chemoradiation portion of this trial. The investigators conclude that "overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer."

Avoiding Radical Surgery

The findings are "very interesting for the one reason that, in the United States in general, we don't try to preserve the bladder, we go for surgery," Chandan Guha, MBBS, PhD, professor and vice chair of radiation oncology at Albert Einstein College of Medicine and Montefiore Medical Center in Bronx, New York, told Medscape Medical News.

"The Europeans, and especially this group from England, have taken the lead in trying to show that if you want, you can do just chemoradiation and essentially avoid radical surgery," he said.

Dr. Guha also noted that, "currently, many urologists in the United States think that cystectomy followed by an artificial bladder is a better way to go than chemoradiation. It is true that if a patient has a relapse after chemoradiation, the surgery becomes more difficult. But as long as the surgeon is willing to do the operation after relapse, the patient can still be cured, survival will not be affected, and they might avoid all the complications of removing the bladder."

Radiation Results From BC2001

Previous results from BC2001, reported in 2012 by Medscape Medical News, came from the chemoradiation portion of the study (n = 360). They showed that adding chemotherapy to sRT was significantly better than RT alone in terms of locoregional recurrence-free survival (hazard ratio, 0.68; 95% confidence interval [CI], 0.48 - 0.96; P = .03).

The radiation portion of BC2001 involved 219 adults with stage T2 to T4a bladder cancer from 28 centers. Patients were randomly allocated to sRT (n = 108) or RHDVRT (n = 111). With RDVRT, the full radiation dose was delivered to the tumor and 80% of the maximum dose was delivered to the uninvolved bladder.

Patients received either 55 Gy in 20 fractions over 4 weeks or 64 Gy in 32 fractions over 6.5 weeks, depending on their cancer center. In the sRT group, the planning target volume (PTV) was the outer bladder wall plus the extravesical tumor extension with a 1.5 cm margin. There were 2 PTVs in the RHDVRT group: PTV1 was as described in the sRT group, and PTV2 was the gross tumor volume plus a 1.5 cm margin.

Late toxicity, defined as RT-related adverse effects at least 1 to 2 years post-treatment, was measured with the Radiation Therapy Oncology Group (RTOG) scale and the Late Effects of Normal Tissue (Subjective, Objective, Management) scale (LENT/SOM). It was lower than anticipated and not significantly different between the sRT and RHDVRT groups.

Comparable Tumor Control

At 2 years, the overall cumulative grade 3/4 RTOG toxicity rate was 13% (95% CI, 8% to 20%). In the 2 groups, the percentage of patients with grade 3/4 toxicity at any specific time point was less than 8%.

"We were unable to demonstrate that RHDVRT results in the anticipated reduction in toxicity," the investigators report. They note that the statistical power to demonstrate effects in the RT-volume comparison was limited, "in part owing to early closure of this component of the 2 × 2 factorial randomization, as a result of slow accrual. Further, the overall incidence of late RTOG toxicity was less than predicted."

The 2 approaches are similarly effective, according to the investigators. The 2-year locoregional recurrence-free rate was 61% in the sRT group and 64% in the RHDVRT group. However, "noninferiority of locoregional control (proof that the RHDVRT treatment was at least not appreciably inferior than the sRT treatment) could not be formally determined in the study," they conclude.

The study was sponsored by the University of Birmingham, supported by Cancer Research UK, and facilitated by the National Institute for Health Research Cancer Research Network. The authors and Dr. Guha have disclosed no relevant financial relationships.

Int J Radiat Oncol Biol Phys. 2013;87:261-269. Abstract


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