Bladder-sparing treatments linked with high rates of progression in NMIBC subset

San Francisco-High-grade nonmuscle-invasive bladder cancer is characterized by high rates of disease progression following introduction of bladder-preservation therapy after treatment with Bacillus Calmette-Guérin (BCG).

Among patients identified with high-grade nonmuscle-invasive bladder cancer from the SEER-Medicare database, only 8.8% of patients received bladder-preservation therapy within 6 months of BCG induction. Among this subset, the rate of progression-free survival (PFS) was only 52.3% at year 5, reported Min Yang, MD, PhD, at the Genitourinary Cancers Symposium in San Francisco.

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“Over the 5-year time frame, what we saw is a high rate of disease progression,” said Dr. Yang, vice president, Analysis Group, Inc., Boston. “Even in year 1, 19% of patients progress. By year 3, more than one third, and by year 5, it’s close to half of the patients. Available treatments are not doing a fair job in terms of slowing progression. What these data are calling for is better treatment. It’s needed for this population.”

The data indicate a high unmet need for novel bladder-sparing therapies to improve outcomes in this difficult-to-treat population.

Cystectomy is the recommended treatment following failure of BCG, but many patients are hesitant to undergo cystectomy and instead choose bladder-preservation therapy, she said.

“We wanted to know what happens after BCG failure,” said Dr. Yang.

Continue to the next page for more.The SEER-Medicare database was used to identify 7,074 patients with high-grade nonmuscle-invasive bladder cancer between 2008 and 2015 who received at least one course of BCG induction (defined as ≥5 weekly instillations). Of these, 620 received bladder-preservation therapy within 6 months of the last consecutive BCG instillation. The most common bladder-preservation therapy was mitomycin C, used in 66.0%, followed by BCG plus interferon alpha (22.9%), valrubicin (Valstar) (4.0%), doxorubicin (Adriamycin) (2.9%), and gemcitabine (Gemzar) (2.1%). Others could include docetaxel (Taxotere), epirubicin (Ellence), nab-paclitaxel (Abraxane), thiotepa (Tepadina), gemcetabine plus docetaxel, and gemcitabine plus mitomycin C.

Half (50.5%) of the patients had a high-grade T1 tumor at diagnosis, 31.1% had high-grade Ta, and 18.4% had carcinoma in situ. The mean number of transurethral resections of bladder tumor prior to the index date was 2.5. Patients received a median of 5.9 BCG instillations, and 85.1% received ≥5.

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The mean Charlson Comorbidity index (CCI) was 1.4. CCI comorbidities included diabetes in 37.9%, chronic pulmonary disease in 31.0%, peripheral vascular disease in 25.8%, congestive heart failure in 19.4%, and renal disease in 17.7%. Other common comorbidities were hypertension (86.0%), dyslipidemia (78.9%), urinary tract infection (78.2%), other malignancies (33.5%), anxiety/depression (32.7%), and Alzheimer’s disease (2.9%).

The rate of PFS at 1, 3, and 5 years was 80.9%, 61.8%, and 52.3%, respectively. Time to progression (TTP) was defined as time from bladder preservation therapy initiation to progression event. In TTP analysis, disease progression occurred in 18.7%, 36.4%, and 45.4% at 1, 3, and 5 years, respectively. Disease progression was predominantly identified by metastases, which accounted for 40.5%, 50.0%, and 50.2% of progression events within 1, 3, and 5 years of bladder-preservation therapy, respectively. At 1, 3, and 5 years, 9.5%, 24.8%, and 32.6% of patients, respectively, had metastases. Progression events as identified by radical cystectomy occurred in 35.1% of progressors during year 1, 30.1% of progressors during year 3, and 30.0% of progression events during year 5. Muscle-invasive bladder cancer accounted for 24.3% of progression events in year 1, 19.9% of events in year 3, and 19.8% of events in year 5.

Ferring Pharmaceuticals, Inc. provided funding for the study. For full disclosures, click here.