Type of BCG affects bladder cancer outcomes

Chicago-Patients with nonmuscle-invasive bladder cancer had significantly better recurrence-free survival (RFS) when treated with the Connaught strain of bacillus Calmette-Guérin (BCG) instead of the Tice strain, according to results of a randomized trial.

Treatment with BCG Connaught (TheraCys) was associated with a 5-year RFS of 75% compared with 46% for BCG Tice (TICE BCG). Median recurrence-free survival also favored BCG Connaught, as reported at the American Association for Cancer Research annual meeting in Chicago.

"This is the first study demonstrating that different BCG strains lead to different clinical outcomes in the treatment of bladder cancer," first author Cyrill A. Rentsch, MD, PhD, a urologist at the University of Basel, Basel, Switzerland, told Urology Times. "Many clinicians have thought that the choice of the BCG strain used to treat bladder cancer did not affect the outcome, but our results indicate that the choice of the BCG strain does impact treatment outcome and favors the use of BCG Connaught over Tice."

In an effort to inform on the debate, investigators in Switzerland performed a prospective study to compare two of the most commonly used BCG strains in Europe and the U.S.-BCG Connaught and BCG Tice.

The study involved 149 patients with high-risk nonmuscle-invasive bladder cancer. All patients underwent transurethral resection of visible tumors, and patients with TaG3 or T1G3 disease underwent a second resection to confirm that all tumor tissue had been resected.

From 2 to 15 days after surgery, patients were randomized to six weekly intravesical instillations of BCG Tice or BCG Connaught. Patients were followed by cystoscopy and bladder wash cytology at 3-month intervals for 3 years, and then every 6 months thereafter. Median follow-up was 25 months, and the primary endpoint was recurrence.

Baseline characteristics did not differ between the treatment groups.

In the BCG Tice group, high-grade T1 disease was most common, accounting for 49% of the total, followed by carcinoma in situ in 22%, high-grade Ta in 19%, and recurrent low-grade Ta in 10%. In the BCG Connaught arm, 54% of the patients had high-grade T1 disease, 22.5% had recurrent low-grade Ta disease, 16% had high-grade Ta tumors, and 7.5% had carcinoma in situ.

Overall, the patients had a 5-year RFS of 61%, but recurrences were significantly more common among patients treated with BCG Tice (n=30) than with BCG Connaught (n=15), said Dr. Rentsch. The median RFS was 22 months for the BCG Tice group and had not been reached in the BCG Connaught arm of the study. The median progression-free and overall survival did not differ significantly at the time of the analysis.

Study's impact on practice uncertain

"I think many clinicians will be surprised by the results because of the belief that the BCG strains are all the same," said Dr. Rentsch. "Whether the study will influence clinical decisions remains to be seen. I think some physicians will be influenced because of the size of the difference in recurrence rates."

Further research is needed to elucidate the underlying mechanisms of action for BCG immunotherapy, he added. Genetic differences between strains could provide direction for additional studies and clinical application.