Sept. 15, 2020
Bacillus Calmette-Guerin (BCG) is frequently in short supply in the United States and across the world. The American Urological Association, together with several other organizations, has put forth recommendations for alternative practices during times of BCG scarcity. These recommendations include prioritizing available doses for induction therapy.
For patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC), induction BCG is considered the mainstay of initial treatment, and maintenance BCG therapy is recommended for patients who had a complete response with induction BCG.
This approach has consistently been found to reduce tumor recurrence, but studies have produced conflicting data on the association of maintenance BCG with disease progression. A team of Mayo Clinic researchers, led by urologic oncologist Stephen A. Boorjian, M.D., of Mayo Clinic in Rochester, Minnesota, conducted a study to analyze the cost-effectiveness of maintenance BCG compared with surveillance after induction BCG for patients with intermediate- and high-risk nonmuscle invasive bladder cancer.
A Markov model was used to evaluate the cost-effectiveness of maintenance BCG. All costs were based on 2018 U.S. Medicare reimbursements and were discounted at a 3% annual rate. The study looked at five-year oncologic outcomes, toxicity rates and utility values from the literature. Univariable and multivariable sensitivity analyses were performed. A threshold of $100,000 per quality-adjusted life year (QALY) per additional QALY was used to define cost-effectiveness.
At five years, mean costs per patient were $14,858 and $13,973 for maintenance BCG and surveillance, respectively. Both strategies yielded a benefit of 4.046 quality-adjusted life years. Since surveillance was just as effective but less expensive than maintenance BCG, the study found surveillance to be the dominant strategy in most clinical scenarios due to lower costs with equivalent effectiveness. In multivariable sensitivity analyses, full-dose and one-third dose maintenance BCG was cost-effective in 17% and 39% of microsimulations, respectively.
However, maintenance BCG became cost-effective if it decreased the five-year bladder cancer recurrence rate by 34.8% relative to surveillance alone. Since this estimate is larger than the vast majority of trials on maintenance BCG, a recurrence benefit alone is unlikely to justify the use of maintenance BCG. Instead, maintenance BCG becomes cost-effective when a 20% recurrence benefit is combined with a progression benefit.
Full-dose maintenance BCG became cost-effective:
- If the absolute reduction in five-year progression was greater than 2.1%. This progression benefit is unlikely to be achieved for intermediate-risk patients with NMIBC because the risk of progression is already very low (less than 6% at five years).
- When maintenance BCG toxicity equaled surveillance toxicity.
Vidit Sharma, M.D., a Mayo Clinic scholar in urologic oncology at Mayo Clinic in Rochester, Minnesota, notes: "While the overall toxicity of BCG is generally acceptable, our study highlights that patients who don't tolerate induction BCG well may actually benefit by forgoing further maintenance BCG. Furthermore, the most cost-effective use of maintenance BCG is in settings where it can realistically amount to a progression benefit. This benefit is more likely to be realized for patients with high-risk nonmuscle invasive bladder cancer, but further research is needed to delineate the progression benefit of maintenance BCG within this high-risk group."
Results of the study to compare the cost-effectiveness of maintenance BCG with surveillance after induction BCG for patients with intermediate- and high-risk nonmuscle invasive bladder cancer were published in the September issue of Journal of Urology.
Maintenance BCG is unlikely to be cost-effective for the overall population of patients with intermediate- and high-risk nonmuscle invasive bladder cancer. Instead, especially in times of BCG shortage, induction BCG should be prioritized, as stated by the American Urological Association's statement.
The study suggests that maintenance BCG may be better reserved for patients with high-risk nonmuscle invasive bladder cancer — particularly those who did not experience major side effects from the initial induction course of BCG — as they are most likely to experience a progression benefit.
Dr. Boorjian notes, "These data are particularly relevant in an era of chronic BCG shortages, where judicious BCG use is paramount to maximizing access for patients most likely to benefit."
For more information
Sharma V, et al. Cost-effectiveness of maintenance bacillus Calmette-Guérin for intermediate and high risk nonmuscle invasive bladder cancer. Journal of Urology. 2020;204:442.