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

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.