TOPLINE:

In patients with non-muscle-invasive bladder cancer, especially those with carcinoma in situ (CIS), most recurrences, progression events, and cystectomies occurred in those with bacillus Calmette-Guérin (BCG)-exposed disease rather than BCG-unresponsive disease, a large retrospective study found. Additionally, only about one quarter of patients received adequate BCG maintenance therapy.

METHODOLOGY:

• Although BCG is the standard of care for non-muscle-invasive bladder cancer, recurrence rates remain high, and adherence to guideline-recommended regimens is often suboptimal.
• To assess the treatment patterns and outcomes of patients with BCG-exposed disease, researchers conducted a retrospective cohort study using Optum’s de-identified Market Clarity Data, linking electronic health records and insurance claims from health systems in the US from January 1, 2007, to June 30, 2024.
• A total of 26,876 patients with non-muscle-invasive bladder cancer (median age at BCG initiation 73 years; 79.5% male) were included, with nearly 36% (n = 9639) having CIS; all patients received at least one full course of BCG induction therapy.
• Adequate BCG therapy was defined as a minimum of four BCG instillations with no more than 3 weeks between doses for induction; adequate maintenance therapy required BCG treatments within 1 year following induction, beginning within 6 months of the induction start date and including at least two doses within 3 months.
• The primary outcome was high-grade disease recurrence within 24 months following completion of BCG therapy. Secondary outcomes included progression to muscle-invasive bladder cancer and radical cystectomy within 24 months, and exploratory outcomes included progression-free survival and cystectomy-free survival.

TAKEAWAY:

• Among 5271 patients with CIS-containing tumors who received adequate BCG induction, 59.3% experienced recurrence within 24 months; among those who recurred, 83.1% were BCG-exposed and 16.9% were BCG-unresponsive.
• Receiving adequate maintenance therapy was associated with better progression-free survival in the overall cohort (hazard ratio [HR], 0.78) and the high-risk CIS cohort (HR, 0.74).
• Among patients with recurrence, those who were BCG-exposed accounted for 83.0% of disease progression cases and 87.8% of cystectomy cases; most of these had received inadequate maintenance therapy (90.2% for progression and 97.0% for cystectomy).
• Adequate BCG maintenance therapy was uncommon across all risk groups, with only 24.9% of patients receiving maintenance therapy, and among high-risk patients with CIS, only 21.1% received adequate maintenance.

IN PRACTICE:

“This cohort study found that patients with BCG-exposed [non-muscle-invasive bladder cancer] represent a large, underserved population and account for most progression and cystectomy events after BCG exposure,” the study authors wrote. “These findings highlight an urgent need for new therapeutic strategies and clinical trial designs targeting this group.”

SOURCE:

The study was led by Maria Giatsoglou, PhD, Pfizer Artificial Intelligence, Data and Analytics Research and Development AI and Data Science, Thessaloniki, Greece. It was published online in JAMA Network Open.

LIMITATIONS:

The data lacked pathology grade and clinical detail, which required use of CIS coding to define a high-risk subgroup and may have excluded high-grade disease without CIS. Because recurrence was the sole primary outcome and no multiplicity adjustment was applied, secondary and exploratory findings should be interpreted as descriptive and hypothesis-generating. Comparisons by maintenance adequacy may be influenced by immortal time bias and residual confounding because adequate maintenance requires patients to remain event-free long enough to complete dosing. Furthermore, analyses were not fully adjusted for age, comorbidities, access-to-care factors, or disease-severity proxies. Finally, the data source represented insured patients within participating US health systems and may not fully represent all patients with non-muscle-invasive bladder cancer nationwide.

DISCLOSURES:

The study was funded by Pfizer Inc. Giatsoglou and Gang Feng, MD, PhD, disclosed owning shares in Pfizer Inc. outside the submitted work. Roger Li, MD, disclosed receiving personal fees from Merck Sharp & Dohme, CG Oncology, ImmunityBio, Pfizer, Johnson & Johnson, AstraZeneca, enGene, Valar Labs, Predicine, and Ferring during the conduct of the study, as well as receiving research support from Predicine, Valar Labs, and Johnson & Johnson. Li also reported serving as scientific advisor or consultant for Bristol Myers Squibb, Merck Sharp & Dohme, CG Oncology, ImmunityBio, Pfizer, Johnson & Johnson, AstraZeneca, enGene, Valar Labs, and Ferring. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.