Introduction:

A large proportion of NMIBC patients become unresponsive to standard-of-care BCG treatment. The recommended subsequent treatment is cystectomy; many patients, however, are medically ineligible or refuse to undergo surgery, and they may be at risk of progression without effective alternative non-invasive treatments. For a deeper understanding of ineligibility or refusal of cystectomy in these patients, country- and demographic-specific reasons were researched.

Methods:

A retrospective chart review was conducted in the EU5, the US, China and Japan from January 2019 to May 2019.  Urologists and medical/clinical oncologists abstracted patient data including demographics, BCG treatment patterns, and use of surgery for BCG-unresponsive patients. BCG-unresponsive status was defined as having at least one of the following: (1) persistent or recurrent carcinoma in situ (CIS) alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, (2) recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, and (3) T1 high-grade disease at the first evaluation following an induction BCG course. Patients were ≥ 18 years and BCG unresponsive for ≥ 3 months prior to data abstraction. Cystectomy status and reasons for cystectomy ineligibility or refusal were captured from the time patients were classified as BCG-unresponsive. Analyses were stratified by country, age, performance status (ECOG) and tumor stage.

Results:

508 physicians abstracted data for 2,554 qualifying patients. Overall, 19% of patients underwent cystectomy, 46% of patients were classed as medically ineligible, and 35% refused cystectomy. Most common reasons for cystectomy ineligibility and refusal, stratified by country are presented in Table 1 and by subgroup in Table 2. Comorbidities (number and type) in the EU5, age (elderly population) in Asia, and risk of post-operative complications in the US were the most common reasons for ineligibility. Comorbidities were a greater factor for patient ineligibility for older age groups (age ≥60), Papillary with CIS, and those with higher ECOG scores (2+). Across countries and subgroups, the desire to conserve the bladder was consistently the most reported reason for patients refusal of cystectomy; however reduction in quality of life (QoL) was an important factor to patient groups with higher ECOG scores (2+ vs <2) and those graded Papillary with CIS tumors.

Conclusion:

81% of patients either refused or were ineligible for cystectomy. Cystectomy refusal and reasons for cystectomy ineligibility varied across countries and patient subgroups. Reasons for refusal of cystectomy were largely due to patients’ desire to conserve their bladder and concerns over impact on patient QoL, irrespective of country and subgroup. These findings highlight that cystectomy is a limited option for BCG-unresponsive patients and therefore there is an urgent need for effective, non-invasive options for subsequent treatment.

Funding: Bristol-Myers Squibb