Reasons for refusal of or ineligibility for radical cystectomy (RC) in patients (Pts) with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) from the SunRISe-1 study.
Authors: Jacob Joseph M , Guerrero-Ramos Félix , Xylinas Evanguelos , Simone Giuseppe , Lotan Yair , Pieczonka Christopher Michael , Arentsen Harm , Necchi Andrea , Kulkarni Girish S. , Patel Manish , Cahn David J , Nam Jong Kil , Boegemann Martin , Hampras Shalaka , Stromberg Katherine , Martin Jason L. , Shulka Abhijit , Sweiti Hussein , Van Der Heijden Michiel Simon 
Published: January 2024

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Background: RC is the recommended treatment (tx) option for pts with BCG-unresponsive HR NMIBC. However, RC is associated with significant risk of morbidity, mortality, and impact on quality of life (QoL); some patients may refuse/be ineligible for RC. In a systemic review of 160 real-world studies, <20% of pts with HR NMIBC recurrent after BCG underwent RC (PMID 35046678). For RC-ineligible pts, bladder-sparing tx is recommended. TAR-200, a novel intravesical drug delivery system that provides sustained release of gemcitabine within the bladder, is under investigation in pts with BCG-unresponsive HR NMIBC who are ineligible for/refuse RC in the ongoing ph 2b SunRISe-1 (SR-1) study (NCT04640623). Preliminary results showed a promising complete response (CR) rate of 73% and durable responses in pts with BCG-unresponsive HR NMIBC treated with TAR-200 (Daneshmand et al. AUA 2023). We report reasons for refusal/ineligibility for RC in pts enrolled in the TAR-200 monotherapy cohort of SR-1. Methods: SR-1 is evaluating the efficacy and safety of TAR-200 + cetrelimab (CET; anti–PD-1) (Cohort 1 [C1]), TAR-200 alone (C2), or CET alone (C3). Pts ≥18 y with histologically confirmed carcinoma in situ (CIS) ± papillary disease (T1, high-grade Ta) who completed adequate BCG and recurred ≤12 mo since last BCG dose with ECOG performance status (PS) of 0-2 are randomized to C1, C2, or C3. As of Amendment 4, pts with papillary disease only will be enrolled in C4 with TAR-200 alone. The primary end point is overall CR rate at any time. Refusal/ineligibility for RC was documented in the electronic case report form. Results: As of Aug 24, 2023, 54 pts were treated in C2. Median age was 71 y (range 40-85). Pts had a median of 12 (range 7-42) prior BCG doses with a median of 3.0 mo (range 0.2-22.0) from last BCG dose to recurrence. Most pts (96%) had ECOG PS 0; 33% had CIS with papillary disease. 50%, 48%, and 19% of pts had a medical history of Gr ≥2 metabolic, vascular, and cardiac conditions, respectively, and 9% were current nicotine users. Overall, 51 (94%) pts refused RC; 3 (6%) were ineligible (Table). The most common reason for refusal was a preference for bladder preservation (52%), followed by concern about QoL (37%). Pts were ineligible for RC due to medical/surgical comorbidities (4%) and age (2%). Conclusions: Most pts enrolled in C2 of SR-1 refused RC, with preference for bladder preservation and QoL concerns being the most common reason for refusal. This highlights the need for bladder-sparing tx options for pts with HR NMIBC recurrent after BCG. Clinical trial information: NCT04640623 . [Table: see text]