Phase 2 LUMBER-NAC compares neoadjuvant platinum chemotherapy (DNA crosslinking) vs upfront cystectomy

Rutgers University is running this Phase 2 randomized study in luminal-subtype muscle-invasive urothelial bladder cancer (cT2N0M0) to test whether skipping neoadjuvant systemic therapy is feasible and oncologically safe in this molecularly defined group. The experimental arm receives physician-chosen standard neoadjuvant systemic therapy—typically cisplatin-based combination chemotherapy such as gemcitabine/cisplatin (cisplatin is a DNA–crosslinking platinum; gemcitabine is a nucleoside analog that blocks DNA synthesis)—followed by radical cystectomy with urinary diversion; the comparator goes straight to cystectomy. The primary signal the trial watches is adverse pathologic upstaging at surgery (pT3–pT4 and/or pN+), a pragmatic safety endpoint for “upfront surgery” strategies. The key scientific angle is subtype selection: luminal MIBC may have different chemo-sensitivity than basal tumors, so this trial operationalizes molecular subtyping to personalize the timing of systemic therapy rather than adding a new drug. Current perioperative options now include chemo-immunotherapy and enfortumab vedotin + pembrolizumab around surgery, making the key question here especially interesting: can a molecularly selected luminal subgroup safely skip neoadjuvant systemic treatment altogether?