The majority of patients diagnosed with bladder cancer have early-stage non-muscle-invasive disease that often can be successfully treated. However, these cancers have a high recurrence rate compared with other solid tumors, and about 20 percent of recurrences progress to more serious muscle-invasive disease.

Transurethral resection of bladder tumor followed by Bacillus Calmette-Guérin (BCG)—a type of intravesical immunotherapy—is the gold standard of treatment for early-stage bladder cancer, recommended by U.S. and European clinical guidelines. However, studies suggest that fewer than one quarter of eligible older patients receive BCG in practice.

A recent analysis co-authored by NYU Langone’s Gary D. Steinberg, MD, professor in the Department of Urology at NYU Langone and director of the Goldstein Urology Bladder Cancer Program at Perlmutter Cancer Center, examines treatment patterns and associated outcomes for patients with early-stage disease included in Medicare’s U.S. Surveillance, Epidemiology, and End Results (SEER) database. Researchers observed that half of patients with intermediate- and high-risk disease did not receive BCG treatment according to guidelines, despite evidence that it improves outcomes.

Dr. Steinberg is a nationally recognized expert in the surgical management of bladder cancer and currently leads several large clinical trials investigating new medications and treatment procedures. His research includes examining the critical need for new agents for patients who are not responsive to BCG therapy or develop resistance to it. For example, one ongoing phase III study is evaluating the immune checkpoint inhibitor pembrolizumab in combination with BCG to potentially improve outcomes and prevent disease recurrence.

Wide Variation in Use of BCG

The recent study by Dr. Steinberg and colleagues reveals wide variations in BCG treatment intensity. Many eligible patients did not receive BCG at all, and among those who did, it was often inadequate, stopping short of ongoing maintenance therapy. Conversely, some patients with low-risk disease received the treatment despite a lack of guideline support.

The retrospective analysis included 39,532 patients over age 65 with early-stage (0–1) urothelial bladder carcinoma diagnosed between 2000 and 2012, according to findings published on July 24, 2020, in Urology. Of the 41 percent who received BCG treatment, only 28.4 percent received adequate therapy. However, at the 12-month point, adequate BCG treatment was associated with decreased risks of recurrence and of cancer-specific and all-cause mortality in patients with intermediate- and high-risk disease.

Although the analysis was not equipped to identify the reasons for such variation, investigators speculated that physicians might be reluctant to give BCG to patients with a high comorbidity burden or other, unknown contraindications. They observed that inadequately treated patients tended to be less healthy than those who received sufficient treatment.

“There seems to be a mismatch in treatment intensity based on disease risk, with many patients receiving too much or too little care,” says Dr. Steinberg. “Overuse of BCG in patients with low-grade disease is also concerning, considering that BCG is in short supply worldwide.”

Practice patterns may also vary according to location, as the study spanned both academic and community care settings, the authors noted. In addition, the analysis does not capture other factors that may have contributed to variability, such as patient refusal of treatment or adverse events that triggered an interruption in treatment.

That said, the study highlights the need for education on appropriate use of BCG, says Dr. Steinberg. In particular, it emphasizes the importance of maintenance therapy, which was not taken into account in several previous studies that did not find an association between treatment intensity and improved survival.

“Our data make it clear that adequate BCG treatment is associated with lower mortality from bladder cancer, especially for patients with higher-risk disease,” he says. “It also stresses the critical role of maintenance BCG in further reducing recurrence and improving survival.”

Disclosures: Gary D. Steinberg, MD, is a member of clinical trial protocol committees for Merck, BMS, Janssen, Cold Genesys, Pfizer, PhotoCure, and Fidia. He is currently or has been a scientific advisor/consultant within the past five years for Heat Biologics, Cold Genesys, PhotoCure, Merck, Roche/Genentech, Ciclomed, Taris Biomedical, MDxHealth, Fidia Farmaceuticals, Urogen, Ferring, Aduro, Boston Scientific, Bristol Myers Squibb, Astra Zeneca, Pfizer, Janssen, Epivax Oncology, Natera, FKD, Ferring, EnGene Bio, SesenBio, BioCanCell, Nucleix, Ipsen, Combat Medical, Astellas, Fergene, Dendreon, Abbvie, and Seattle Genetics. Dr. Steinberg has equity stock/options in Epivax Oncology and Urogen.