Subgroup Analysis Shows No Key Differences Between High-Grade Recurrence, Cancer Progression Outcomes in BCG-Unresponsive NMIBC

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No significant clinical differences were identified regarding cancer progression, high-grade recurrence, or cystectomy rates among subgroups of patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), according to data from a retrospective subgroup analysis.

These data, which were presented at the 2025 American Urological Association Annual Meeting, challenge clinical practices operating on the assumption that patients with high-grade T1 disease following induction have more aggressive disease and would benefit from upfront cystectomy.

The subgroup analysis included 3 subgroups of patients: those with high-grade T1 disease after induction of BCG (n = 28), recurrent high-grade Ta/T1 disease within 6 months of adequate BCG (n = 49), and persistent or recurrent carcinoma in situ (CIS) within 12 months of adequate BCG (n = 43). Among these respective subgroups, the median progression-free survival (PFS) was 25.5 months (IQR, 15.6-32.9), 18.8 months (IQR, 7.8-36.8), and 11.6 months (IQR, 5.9-32.1).

“Although we hypothesized that earlier time-to-meeting BCG-unresponsive designation would be associated with worse outcomes, we found no [effect] of the amount of maintenance BCG received on PFS,” lead study author Ketty Bai, BS, a 4th-year medical student at Columbia University Irving Medical Center in the Department of Urology in New York, and colleagues wrote on a poster presentation of the data. “[However, limitations included] differences in therapies received after BCG-unresponsive therapy [which] may have affected survival outcomes and a single institution experience that was retrospective in nature.”

Background and Subgroup Analysis Overview

With a significant gap in literature regarding the degree of heterogeneity between subgroups of patients with BCG-unresponsive NMIBC and its impact on prognosis and response to treatments, the analysis aimed to compare PFS and high-grade recurrence-free survival (RFS) outcomes among the 3 subgroups with implications for patient selection criteria for trials and FDA approvals of emerging therapies; and prognosis based on the length of BGC therapy received before becoming BCG unresponsive.

Data from patients included in an institutional database from 2003 to 2022 were collected (n = 727), and patients who met the criteria for BCG-unresponsive NMIBC were identified (n = 120) and sorted into the subgroups of high-grade T1 disease after induction, high-grade Ta/T1 disease within 6 months, and CIS within 12 months.

Of note, the primary outcome of interest was PFS, defined as progression to T1, muscle-invasive, or metastatic disease. Patients were further stratified based on the number of maintenance doses received before BCG-unresponsive designation. Secondary outcomes of interest included high-grade RFS, cystectomy-free rate, and overall survival.

Baseline Patient Characteristics

Among the 3 subgroups—high-grade T1 after induction, high-grade Ta/T1 within 6 months, and CIS within 12 months, respectively—the median ages were 70.1 years (IQR, 62.1-78.8), 71.3 years (IQR, 66.6-79.0), and 69.7 years (IQR, 64.8-76.0). In all subgroups, the majority were male (67.9%; 69.4%; 69.8%). Patients were White (85.7%; 87.8%; 95.4%), Black (3.6%; 2.0%; 2.3%), Asian (0%; 4.1%; 0%), or other (10.7%; 6.1%; 2.3%). Additionally, more than half were current or former smokers (53.6%; 65.3%; 69.8%). Stages at initial diagnosis included Tis (7.1%; 18.4%; 48.8%), Ta (21.4%; 34.7%; 23.3%), T1 (71.4%; 42.9%; 27.9%), and concomitant CIS (50%; 40.8%; 74.4%). Notably, upfront cystectomy was received in 10.7%, 10.2%, and 4.7% of patients from the respective subgroups. The median follow-up was 5.9 years, 5.7 years, and 6.4 years, respectively.

Additional Survival Data and Future Directions

The median high-grade RFS, excluding patients who underwent upfront cystectomy was 12.9 months (IQR, 3.7-17.3), 8.9 months (IQR, 4.5-16.0), and 5.2 months (IQR, 3.5-14.7) among patients from the high-grade T1 after induction, high-grade Ta/T1 within 6 months, and CIS within 12 months subgroups.

“No significant difference in PFS was found among those who received varying lengths of maintenance BCG prior to BCG-unresponsive designation,” the study authors wrote in the poster.

As bladder-sparing treatments continue to emerge in the NMIBC landscape, the potential implications of the BCG-unresponsive subgroup on response to these treatments should be explored as a future direction, the authors concluded.

Reference

Bai K, Pingle SR, Chung R, et al. Assessing clinical differences within BCG-unresponsive NMIBC: a subgroup analysis with treatment implications. Presented at: 2025 American Urological Association Annual Meeting; April 26-29, 2025; Las Vegas, NV. Abstract IP02-37.