BERLIN—Radiotherapy is a viable alternative to surgery for invasive bladder cancer, according to a study presented at the joint congress of the European Cancer Organization and European Society for Medical Oncology.

Robert Huddart, MD, a reader in urological oncology at The Institute of Cancer Research (ICR), Sutton, UK, reported the results from BC2001, a trial coordinated by the ICR and the University of Birmingham.

In the trial, investigators examined whether modifying the volume of bladder exposed to high-dose radiotherapy would reduce late toxicities without increasing the risk of recurrence. Volume has been shown to be a determinant of toxicity, and data suggest that reducing high-dose volume may reduce toxicity and allow dose escalation, Dr. Huddart explained.

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He and his colleagues randomized patients to receive standard radiotherapy—which involved delivery of radiation to an empty whole bladder and tumor plus a 1.5-cm margin—or to a reduced high-dose volume arm, in which 80% of the total radiotherapy dose was administered to the uninvolved bladder and 20% of dose was delivered to the tumor, with a 1.5-cm margin. Radiation could be delivered according to one of the two UK standard fractionation schedules: over a four-week schedule (55 Gy/20 fractions) or a 6.5-week schedule (64 Gy/32 fractions).

Dr. Huddart presented data on the first 219 patients entered into the radiotherapy volume comparison. After a median follow-up of three years, both treatment arms had excellent rates of disease control, with no differences in survival, recurrences or invasive recurrences, Dr. Huddart reported. Local or regional disease-free survival was 71.8% with standard radiotherapy and 74.4% with reduced high-dose volume radiotherapy, a nonsignificant difference between the groups.

To date, the researchers identified 64 pelvic recurrences, of which 32 were bladder-invasive (less than 15% of patients overall). Fewer than 10% of patients required a salvage cystectomy, with no difference between the arms, he said.

The overall survival for the entire cohort was more than 60% at two years and 40% at four years. Two-year survival was 60.8% with standard radiotherapy and 64% in the experimental arm, which was not significantly different.

“This [survival rate] is similar to that seen for cystectomy series, despite a median age of participants of over 72 years. Most cystectomy series have median ages in the mid-60s,” he noted.

Toxicity was assessed by physician-assessed rating scales, patient-completed questionnaire, and measurement of maximum bladder capacity. The overall level of toxicity was less than predicted, Dr. Huddart noted. Rather than an expected cumulative RTOG grade 3-4 rate of 40% we noted cumulative rates of less than 12%, with rates of 3%-4% at any point, he said.

Quality of life diminished toward the end of the radiotherapy treatment but recovered to baseline levels by six months, both in terms of overall score and in the individual domains. Levels at or above baseline were maintained throughout subsequent follow-up.

Although investigators hoped to observe less toxicity with the reduced high-dose volume approach, no real improvements over standard radiotherapy were seen according to physician assessment or patient-reported scales. This may be due to lower toxicity overall, small sample size, and the use of improved radiotherapy techniques, Dr. Huddart said.

The one measure, however, that was significantly different for this arm was bladder capacity. Radiotherapy to the whole bladder can induce fibrosis, which reduces bladder capacity. In the standard radiotherapy group, there was a small but significant decrease in mean bladder capacity at 12 and 24 months, and this was not seen in the reduced high-dose volume group, he reported.

“The good rates of local control and overall survival, combined with low rates of toxicity and excellent quality of life, are good news for muscle invasive bladder cancer patients, and suggest that modern radiotherapy is a viable alternative to surgery for patients with this disease,” Dr. Huddart concluded. “We believe we may be able to further improve tumor control rates either by the use of combination therapies or image-guided radiotherapy dose escalation.”