1-year survival predicts response to BCG therapy

Atlanta-Up to half of all bladder cancer patients receiving Bacillus Calmette-Guérin (BCG [TheraCys, TICE BCG]) therapy will fail to respond or relapse within 5 years, but those who make it through the first year have a better chance at responding to subsequent therapy than those who fail sooner. The response rate of those who fail after a year is similar to the response rate of patients who have yet to receive their first treatment, according to a University of Iowa study presented at the AUA annual meeting.

"We had a large database and we wanted to try to determine which patients who recur after treatment will benefit from repeat intravesical therapy," said Brian Gallagher, MD, a urology resident working with Michael A. O'Donnell, MD, at the University of Iowa Hospitals, Iowa City.

The database was indeed substantial. The initial findings of the phase II trial of BCG plus interferon-alpha published in the Journal of Urology (2004; 172:888-93) involved 490 patients who were BCG-naive (BCG-N) or had failed a previous BCG treatment (BCG-F). The database had expanded considerably by 2006: Dr. Gallagher was able to report on 536 BCG-N patients and 467 BCG-F patients who presented with recurrent superficial disease.

Dr. Gallagher was able to make a number of important observations, the first of which concerned the different response rates to subsequent BCG therapy among those who failed the initial therapy within 1 year and those who failed after 1 year. The reason for the difference in response rates is not known.

"Those who failed early had a much poorer response rate to treatment with intravesical therapy," he said. "We don't know why that is. We don't know if the tumor biology was different or the tumors have become immunoresistant to the therapy. The bottom line is that they do not respond well [to further intravesical BCG plus IFN] and perhaps should be considered for other therapies.

"Perhaps those that are recurring after 1 year have developed a completely new tumor and that is why the response rates are similar to BCG-N."

Number of treatments

Among the other observations made in the study were that the number of prior BCG treatments did not significantly affect responses to subsequent BCG plus IFN treatments in those patients who failed after 1 year of therapy. The authors concluded that such patients should be considered for another course of therapy irrespective of the number of treatments they may already had been given.

The authors cautioned, however, that the number of patients in the subgroup of patients who received more than three courses of BCG was small. The study noted no difference between those patients who failed treatment after 12 months and those who failed after 24 months.

The data also allowed the Iowa team to identify a number of factors that appeared to have no influence on outcomes. These were gender, cancer grade, tumor size (<1 cm vs. 1 to 5 cm), previous transurethral bladder resection, maintenance therapy, or prior chemotherapy.

The cancer-free survival rate at 24 months was 59% for BCG-N patients compared with 45% for BCG-F patients. BCG-F patients who recurred immediately (refractory patients), who recurred <6 months, 6 to 12 months, >12 months, and >24 months had cancer-free survival rates of 34%, 41%, 43%, 53%, and 66%, respectively. As background, the authors noted that despite the success of BCG therapy, 30% to 50% of patients will fail to respond or relapse within 5 years and that BCG-refractory patients had progression rates of up to 60%.