Introduction:

Bacillus Calmette-Guérin (BCG) is the standard of care (SOC) for the treatment of patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). However, up to 40% of patients ultimately become unresponsive to BCG, increasing the risk of disease recurrence and progression. Previous research has shown that intravesical chemotherapy is the most common treatment for patients with BCG-unresponsive HR-NMIBC with carcinoma in situ (CIS) in the US. However, real-world studies often rely on treatment duration and healthcare resource utilization as proxies for effectiveness. This is due to limited or unavailable detailed data on treatment response and recurrence in structured data sources, such as payer claims and electronic health records (EHR). For this analysis, we conducted a manual chart review of this population to enhance existing data and better understand real-world treatment outcomes following intravesical chemotherapy after becoming BCG-unresponsive, including complete response (CR), duration of response (DOR), and event-free survival (EFS).

Methods:

This retrospective study utilized both patient charts and EHR from American Urological Association’s Quality (AQUA) Registry, linked to healthcare      claims for comprehensive treatment data. CR and high-risk recurrence were manually abstracted from unstructured clinical notes. CR was confirmed by normal cystoscopy, negative urine cytology or pathology, or physician documentation; recurrence was confirmed by positive TURBT or biopsy with high-grade Ta, T1 or CIS. Adults who received ≥7 BCG doses within 6 months between 2015-2022 and initiated intravesical chemotherapy (index) within a year of adequate BCG for CIS recurrence were included. Baseline characteristics and any time CR were described. DOR in responders and EFS in all patients were evaluated using Kaplan-Meier methods. DOR was defined as time from first CR to the first high-risk recurrence, treatment change, progression to ≥T2 stage or metastatic disease, or death; EFS events included persistent disease at the first disease assessment, high-risk recurrence, progression, or death.

Results:

134 patients with HR-NMIBC CIS who initiated intravesical chemotherapy after becoming BCG-unresponsive met study criteria. Median age was 75 years (range 55–88), 82.1% were male, and 91.3% were White; 67.2% of patients had CIS only, while 32.8% had CIS with papillary tumor. The median number of prior BCG doses was 12 (range 7–19). Most used intravesical chemotherapy was mitomycin (36.6%) and gemcitabine (29.9%). Overall, 26.1% of patients treated with any intravesical chemotherapy achieved CR at some point before switching treatments (ranging 22.4% to 40.0% across individual chemotherapies). Among those who achieved CR (n=35), the median DOR was 8.8 months (95% CI: 7.17–40.60 months; Figure 1), with 51% patients experiencing high-risk recurrence, treatment change, progression, or death by 9 months. In all patients, median EFS was 3.8 months (95% CI: 3.29–4.57), with 76% of patients experiencing persistent disease, high-grade recurrence, progression, or death ≤12 months (Figure 2).

Conclusion:

Despite being the current standard treatment for BCG-unresponsive HR-NMIBC patients with CIS, real-world data from this urology practice network indicate that only a small proportion of patients achieve CR with intravesical chemotherapy. Among responders, the responses were not often durable. Median EFS was modest, with many patients experiencing persistent disease, recurrence, progression, or death within a short timeframe. Findings highlight the significant need for additional effective, durable, tolerable bladder-sparing options for this high-risk population. Limitations include the retrospective nature, lack of central pathology review, and potential missing or unknown data that might confound the results.

Funding: Johnson and Johnson