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.
Maintenance treatment has been controversial, since the successful preliminary experience 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 situ transitional cell bladder carcinoma who were randomized to maintenance or no maintenance after a six-week BCG induction. Maintenance was three weekly instillations of BCG at three months and six months, then every six months for three years.
The analysis was based on 385 eligible patients who were disease-free at the time of randomization. Worsening disease was defined as pathologic progression 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 median time to recurrence of 75 months for maintenance vs 36 months for controls.
Progression-free survival was also significantly better, and there was a 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 at risk for invasion, ie, those with grade 2 or 3 lamina propria invasive disease, he said, and was not seen in those with grade 1, Ta tumors.
"We did not aggressively encourage these early patients to stay on maintenance, but now, as the data mature, we firmly believe BCG maintenance will 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 regimens are compared.
Compliance a Problem
Not all patients got a complete course: Compliance was 95% for the first maintenance 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. "Patients just got tired of coming in for treatment," he said.
At the meeting's highlights session, Dr. James Montie, professor of urology, the University of Michigan, said that the SWOG study "tells us we should be using maintenance therapy. You can integrate this into your 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 greatly improved disease progression and survival in patients with transitional cell bladder carcinoma.
Over a 10-year period, 133 patients underwent surgery, 102 with stage T1 disease and 31 with carcinoma in situ, either primitive or high-grade. Patients were randomized to additional BCG therapy or no therapy after surgery, and were assessed at two years.
Greater disease progression was noted in patients not receiving BCG after surgery: 48 of 72 controls vs 25 of 61 BCG patients, for a 26% significant difference.
There were 12 cancer deaths cancer in the 61 BCG patients and 39 in the 72 control patients, for a 34% significant difference. Overall survival was 26% greater for the BCG-treated patients, Dr. von Heland reported.
"Treatment was an important protective factor," he said, "producing a relative risk of only 0.31." Carcinoma in situ association and focality were significant predictors of poor outcome in these patients, he added.
Cost-Effectiveness Study
Dr. Kerry Kilbridge, of Brigham and Women's Hospital, presented data showing that BCG is an extremely cost-effective therapy. Using a Markov decision-making model to quantify the risks and benefits of treatment vs non-treatment in a 65-year-old male with high-grade, recurrent transitional cell 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 year of life saved was $1,526. "In comparison, to diagnose and treat a cancer of unknown primary is $2,400,000 per year of life saved, and autologous bone marrow transplantation is $115,000," she said.
