In a multicenter phase III trial of 360 patients with muscle-invasive bladder cancer, synchronous chemoradiotherapy provided better locoregional control without significant added toxicity, investigators for the Bladder Cancer 2001 trial have found.
Study results were reported online first on April 19, in the New England Journal of Medicine.
“Removing the bladder is still one of the most effective ways of treating invasive cancer that has spread to the muscle of the bladder. But this can be very distressing and we know patients are often too frail for such radical surgery,” said lead author Nicholas D. James, MB, BS, PhD, from the University of Birmingham, School of Cancer Sciences, Edgbaston, Birmingham, UK.
“The alternative is to give radiotherapy, but around a third of these patients will go on to relapse with invasive disease and will need their bladder removed anyway. So these results really provide a lifeline for those too old or weak for surgery and mean that, in the future, fewer patients will need their bladder removed.”
For the study, patients were randomly assigned to radiotherapy alone or to radiotherapy with chemotherapy, which consisted of fluorouracil(Drug information on fluorouracil) (at 500 mg/m2/day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin(Drug information on mitomycin) C (12 mg/m2) on day 1. (In addition, patients were randomly assigned to treatment with either whole-bladder radiotherapy or modified-volume radiotherapy, but those results were not reported in the NEJM article.)
The primary end point was survival free of locoregional disease, and secondary end points included overall survival and toxicity.
The investigators reported that, at 2 years, rates of locoregional disease–free survival were 67% in the chemoradiotherapy group and 54% in the radiotherapy group. With a median follow-up of nearly 6 years (69.9 months), the hazard ratio in the chemoradiotherapy group was 0.68 (P = .03).
Five-year rates of overall survival were 48% in the chemoradiotherapy group vs 35% in the radiotherapy group (NS; P = .16). During treatment, grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group (36.0% vs 27.5%, P = .07) but this was not the case during follow-up (8.3% vs 15.7%, P = .07).