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Long-term outcomes of a cascading salvage strategy for high-risk non-muscle-invasive bladder cancer
Journal article   Open access   Peer reviewed

Long-term outcomes of a cascading salvage strategy for high-risk non-muscle-invasive bladder cancer

Ian M McElree, Ryan L Steinberg, Helen Y Hougen, Sarah L Mott, Vignesh T Packiam and Michael A O'Donnell
BJU international, Vol.137(2), pp.339-347
02/2026
DOI: 10.1111/bju.70044
PMCID: PMC12789842
PMID: 41121991
url
https://doi.org/10.1111/bju.70044View
Published (Version of record) Open Access

Abstract

To report long-term oncological outcomes of patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) undergoing bladder-sparing therapy (BST) after bacillus Calmette-Guérin (BCG) failure. We retrospectively reviewed patients with HR-NMIBC treated from 2000 to 2025 with intravesical therapies after BCG failure, all of whom received salvage gemcitabine/docetaxel (Gem/Doce). Subsequent BST included valrubicin/docetaxel, sequential doxorubicin/gemcitabine alternating with mitomycin-C/docetaxel, and gemcitabine/cabazitaxel with pembrolizumab. Kaplan-Meier analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), cystectomy-free survival (CFS), and cancer-specific survival (CSS). A total of 85 patients with HR-NMIBC were included of whom 38 (45%) were BCG-unresponsive. The median (interquartile range) follow-up was 86 (43-108) months from induction Gem/Doce. Following Gem/Doce initiation, RFS did not significantly decline with each successive line of salvage therapy: among patients treated with first (Gem/Doce), second, and third line salvage therapy, the 2-year RFS was 47%, 43%, and 39%, respectively (P = 0.68). Overall, the PFS at 5 years was 81% (95% confidence interval [CI] 69-88%). PFS did not significantly decline with each successive salvage line of therapy: among patients treated with first (Gem/Doce), second, and third line salvage therapy, the 2-year PFS was 91%, 88%, and 93%, respectively (P = 0.98). CFS and CSS were 74% (95% CI 62-83%) and 88% (95% CI 79-94%) at 5 years, respectively. Multi-line BST is feasible and can yield durable bladder preservation and oncological control in select patients with HR-NMIBC following BCG failure. Progression-free outcomes remained favourable across successive lines of salvage therapy. These findings support the role of longitudinal BST as an alternative to radical cystectomy in carefully and appropriately selected patients.
 Chemotherapy urinary bladder neoplasms clinical protocols urinary bladder BCG

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