Efficacy of BCG Maintenance in Bladder Cancer Is Confirmed

June 1, 1997

NEW ORLEANS--A large SWOG study presented at the American Urology Association (AUA) meeting confirms the efficacy of Bacillus Calmette-Guerin (BCG) as maintenance therapy for superficial bladder cancer, and a report from Italy shows its benefits as an adjuvant to surgery.

NEW ORLEANS--A large SWOG study presented at the American Urology Association(AUA) meeting confirms the efficacy of Bacillus Calmette-Guerin (BCG) asmaintenance therapy for superficial bladder cancer, and a report from Italyshows its benefits as an adjuvant to surgery.

Maintenance treatment has been controversial, since the successful preliminaryexperience with the drug has not been consistently validated, Donald Lamm,MD, said in his presentation of the SWOG results.

This trial (SWOG 8507) included 550 patients with Ta, T1, or in situtransitional cell bladder carcinoma who were randomized to maintenanceor no maintenance after a six-week BCG induction. Maintenance was threeweekly instillations of BCG at three months and six months, then everysix months for three years.

The analysis was based on 385 eligible patients who were disease-freeat the time of randomization. Worsening disease was defined as pathologicprogression to stage T2 or higher, or need for chemotherapy, radiotherapy,or cystectomy.

The maintenance group had significantly superior recurrence-free survival,compared with no maintenance: 96 vs 135 events, respectively, and a mediantime to recurrence of 75 months for maintenance vs 36 months for controls.

Progression-free survival was also significantly better, and there wasa nonsignificant trend toward better overall survival, reported Dr. Lamm,professor of urology, West Virginia University.

'Something We Can Advocate Now'

The advantage in disease progression was limited to these patients atrisk for invasion, ie, those with grade 2 or 3 lamina propria invasivedisease, he said, and was not seen in those with grade 1, Ta tumors.

"We did not aggressively encourage these early patients to stayon maintenance, but now, as the data mature, we firmly believe BCG maintenancewill reduce mortality. This is certainly something we can advocate now,but only in patients capable of stimulating an immune response," Dr.Lamm said. He added that BCG should be the standard with which new regimensare compared.

Compliance a Problem

Not all patients got a complete course: Compliance was 95% for the firstmaintenance dose, 77% at six months, 30% at 24 months, and 16% at 36 months.About a quarter of patients had grade 3 or 4 toxicities, which caused 10%to drop out. But there were other reasons for not completing therapy. "Patientsjust got tired of coming in for treatment," he said.

At the meeting's highlights session, Dr. James Montie, professor ofurology, the University of Michigan, said that the SWOG study "tellsus we should be using maintenance therapy. You can integrate this intoyour practice now."

Italian Treatment Study

A study presented by Dr. Magnus von Heland, of the University La Sapienza,Rome, found that adding BCG therapy to transurethral resection greatlyimproved disease progression and survival in patients with transitionalcell bladder carcinoma.

Over a 10-year period, 133 patients underwent surgery, 102 with stageT1 disease and 31 with carcinoma in situ, either primitive or high-grade.Patients were randomized to additional BCG therapy or no therapy aftersurgery, and were assessed at two years.

Greater disease progression was noted in patients not receiving BCGafter surgery: 48 of 72 controls vs 25 of 61 BCG patients, for a 26% significantdifference.

There were 12 cancer deaths cancer in the 61 BCG patients and 39 inthe 72 control patients, for a 34% significant difference. Overall survivalwas 26% greater for the BCG-treated patients, Dr. von Heland reported.

"Treatment was an important protective factor," he said, "producinga relative risk of only 0.31." Carcinoma in situ association and focalitywere significant predictors of poor outcome in these patients, he added.

Cost-Effectiveness Study

Dr. Kerry Kilbridge, of Brigham and Women's Hospital, presented datashowing that BCG is an extremely cost-effective therapy. Using a Markovdecision-making model to quantify the risks and benefits of treatment vsnon-treatment in a 65-year-old male with high-grade, recurrent transitionalcell carcinoma ± carcinoma in situ, she found that BCG cost only$873 more than surgery alone.

Offering a gain of six months in life expectancy, the cost per yearof life saved was $1,526. "In comparison, to diagnose and treat acancer of unknown primary is $2,400,000 per year of life saved, and autologousbone marrow transplantation is $115,000," she said.