NEW YORK (Reuters Health) - Treatment with chemotherapy plus radiation therapy (RT) is a viable alternative to radical surgery in some patients with muscle invasive bladder cancer, according to presentation at Monday's plenary session of the American Society for Radiation Oncology (ASTRO) annual meeting.
Combination treatment improved locoregional disease-free survival by nearly 40% compared with RT alone after about three years in this phase III trial, reported Dr. Nicholas James, an oncologist at the University of Birmingham, U.K.
Between 2001 and 2008, the investigators randomly assigned 182 patients with muscle invasive bladder cancer (pT2-T4a N0 M0) to chemotherapy plus RT (chemoRT) and 178 to RT alone. Mean age was 73, with about 15% of patients in their 80s, Dr. James told Reuters Health in an e-mail.
Depending on the center, RT was given as 64 Gy in 32 fractions over 6.5 weeks or 55 Gy in 20 fractions over four weeks. Chemotherapy was mitomycin C (12 mg/m2 intravenous bolus on the first day of RT) and 5-fluorouracil (500 mg/m2/24 hours for five days during week one and five days during week four).
Locoregional disease-free survival at two years was 71% in the chemoRT group and 58% in the RT group. The corresponding hazard ratio at a median follow-up of 40 months was 0.61 (p = 0.01).
Two-year overall survival was 63% with chemoRT and 58% with RT (40-month HR = 0.78, p = 0.10).
During the trial, 8.8% in the chemoRT group underwent cystectomy, vs. 12.4% in the RT group (p = 0.27).
How do these outcomes compare with patients treated with surgery as first-line treatment?
"It's very hard to compare, as our patients are mostly older and less fit than those in surgical series," Dr. James answered. "Overall survival in large pooled surgical series is around 45%, so our five-year survival in the chemoRT arm of 50% looks pretty comparable."
The dose of chemo was so low that adverse effects were due to radiation and didn't differ significantly between groups, he noted. "Main toxicities were radiation cystitis and proctitis, mostly grades 1-2. RT completion rates were > 95% in both arms and hence were mostly not dose limiting," he added.
Dr. James pointed out that in the U.K., more of these patients are treated with RT than with surgery, whereas nonsurgical treatment is considered experimental in the U.S.
Appropriate candidates for chemoRT, he suggested, would include "older, less fit patients at high risk of surgical complications" and patients receiving neoadjuvant chemo prior to RT/surgery "if they get a good response to the chemo."
He considers cystectomy a better option for patients with multiple tumors or poor bladder function ("i.e., not worth preserving").
In a new study, Dr. James's group will add the anti-EGFR antibody cetuximab to their chemoRT regimen.
Concluding, Dr. James said, "I think more patients should be offered chemoRT as a viable alternative to radical surgery."
According to Dr. Arnab Chakravarti, "For quality-of-life reasons, bladder-sparing options are being actively investigated." Dr. Chakravarti is chair of the department of radiation oncology at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. He was not one of the trial investigators.
"This study seems to show that combined chemo and RT appears to be superior to RT alone. Combined chemoRT also seems to be relatively safe vs. RT alone, with no increase in toxicity."
"What should be kept in mind," he added, "whether treatment is surgical or with bladder preservation, about half of these patients eventually develop metastatic disease, so the challenge here is not only local control but also prevention of distant metastasis."
By Karla Gale
Last Updated: 2010-11-03 15:00:02 -0400 (Reuters Health)
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