Two studies underscore need for more effective, bladder-sparing therapies in high-risk cancer

For decades, Bacillus Calmette-Guérin (BCG) immunotherapy has remained the cornerstone of treatment for patients with high-risk nonmuscle-invasive bladder cancer (HR-NMIBC). Yet for many older adults, the benefits are limited, and once BCG fails, few effective options remain.

Two companion studies presented at the AMCP Nexus 2025 meeting in October 2025 and published as posters in the Journal of Managed Care & Specialty Pharmacy the same month provide true real-world pictures of what happens to these patients, highlighting both the clinical and economic burdens of recurrence and the urgent need for more durable, bladder-sparing therapies.

In one study, Honghao Fang of Analysis Group Inc., along with colleagues from Merck & Co., UT Southwestern Medical Center and other institutions, analyzed real-world outcomes and costs among older adults receiving BCG. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2007 to 2020, the researchers identified 5,490 patients aged 65 years and older who received guideline-recommended treatment for HR-NMIBC.

“High-risk NMIBC is typically managed with transurethral resection of the bladder tumor followed by BCG,” the researchers wrote. “Understanding the clinical outcomes and associated disease management costs under the current standard of care is essential for guiding the adoption of emerging treatments.”

Patients were followed for a median of 2.9 years, with a median age of 76. Disease recurrence was classified as nonmuscle-invasive relapse, progression to muscle-invasive bladder cancer (MIBC), or distant metastasis. Kaplan-Meier analyses estimated recurrence-free and overall survival, while bladder cancer–related disease management costs were tracked across different health states. Recurrence-free periods in the first two years carried the lowest mean costs, but these rose sharply once the disease recurred or progressed.

The findings showed that disease progression not only worsens patient outcomes but also significantly increases overall healthcare costs. Late-stage disease and post-recurrence cystectomy were associated with the highest expenditures, largely driven by hospitalization, procedures and end-of-life care.

The researchers noted that prolonging recurrence-free survival and delaying progression to MIBC could help mitigate these costs and improve patient outcomes.

“Our results highlight the importance of improving the durability of the BCG response and delaying progression to muscle-invasive disease to help mitigate costs,” they wrote.

A second related study led by Monika Raut of Merck & Co. and conducted in collaboration with Analysis Group focused on the subset of patients who become BCG-unresponsive. Using the same SEER-Medicare dataset, the investigators examined real-world treatment patterns and recurrence rates among older patients with BCG-unresponsive HR-NMIBC with carcinoma in situ (CIS) who received bladder-sparing therapy rather than cystectomy.

“Among patients who are BCG-unresponsive HR-NMIBC with carcinoma in situ, there are limited data on recurrence and next treatments received,” the researchers wrote.

In the study, patients were considered unresponsive if they received adequate induction therapy — defined as at least five BCG treatments within 70 days — and adequate maintenance (at least two instillations within 180 days) before discontinuing treatment, followed by additional therapy within one year.

The study identified subsequent recurrences through claims for transurethral resections, intravesical or systemic chemotherapy, radiotherapy, pembrolizumab initiation or cystectomy.

Despite multiple subsequent interventions, the data showed that recurrence and progression remain common. Many patients underwent repeated intravesical treatments before eventually requiring cystectomy or systemic therapy.

“The results underscore that many patients continue to receive multiple lines of intravesical therapy even after becoming BCG-unresponsive, delaying definitive treatment,” the authors wrote.

This pattern of ongoing recurrence not only places a heavy toll on patients but also increases costs. Repeated intravesical treatments, ongoing monitoring and delayed definitive therapy contribute to escalating costs and poorer survival outcomes.

“Improved identification of truly unresponsive patients and earlier transition to effective alternatives could enhance both survival and quality of life,” the researchers wrote.

Together, these studies depict a challenging treatment landscape for HR-NMIBC and BCG-unresponsive disease. While BCG remains the standard of care, the recurrence rates and associated costs underscore its limitations, especially for older adults who are often poor candidates for radical surgery. Both studies point to an urgent need for new, effective bladder-sparing treatments, such as intravesical gene therapy and checkpoint inhibitors, to improve durability of response and reduce progression.