Advanced bladder cancer patients who cannot tolerate standard chemotherapy have long faced limited treatment options before undergoing radical surgery. This population—representing roughly 40% of muscle-invasive bladder cancer cases—typically proceeds directly to cystectomy with uncertain long-term outcomes.
A randomized trial involving 344 patients demonstrated that combining enfortumab vedotin with pembrolizumab before and after surgery dramatically improves cancer control. The dual immunotherapy approach reduced the risk of disease recurrence or death by 63% compared to surgery alone. At two years, 74.7% of patients receiving the combination therapy remained event-free versus only 39.4% in the surgery-only group. The nectin-4-targeted antibody-drug conjugate delivered in nine cycles alongside 17 cycles of the PD-1 inhibitor created sustained anti-tumor immunity.
This represents a paradigm shift for cisplatin-ineligible bladder cancer management, addressing a significant unmet need in urologic oncology. The combination leverages complementary mechanisms: enfortumab vedotin delivers cytotoxic payload directly to cancer cells expressing nectin-4, while pembrolizumab unleashes T-cell responses against tumor antigens. However, the perioperative approach requires careful patient selection and toxicity monitoring across an extended treatment timeline. The trial's 25-month median follow-up provides encouraging early signals, though longer observation will clarify durability of responses and late toxicity profiles. For eligible patients, this dual-agent strategy could transform outcomes in a historically challenging clinical scenario where surgical resection alone often proves insufficient for long-term disease control.