Management of Clinically Regional Node-Positive Urothelial Carcinoma of the Bladder

Purpose of Review Clinically regional node-positive (cN+) urothelial carcinoma of the bladder requires a multi-modal management approach amidst growing recognition that it represents a spectrum of disease. Herein, we review the contemporary evidence for the natural history, evaluation, and management of clinically regional node-positive urothelial carcinoma of the bladder, highlighting recent changes in lymph node staging. Recent Findings Despite advances in techniques, cross-sectional imaging remains relatively insensitive for the detection of lymph node metastases. Recent changes to nodal staging that distinguish between cN1, cN2–3, and non-regional lymph node metastases reflect an increasing understanding that node-positive disease is heterogeneous and its management must be individualized according to nodal staging. Systemic therapy remains the initial management strategy, either alone or in conjunction with radiotherapy, with choice and sequencing of agents extrapolated from studies of metastatic disease. Consolidative radical cystectomy is an option for patients with disease response to upfront systemic therapy, and several series demonstrate a subset of patients with favorable oncologic outcomes. The comparative effectiveness of radiotherapy and radical cystectomy as local therapy remains an important evidence gap. Future studies that identify predictive biomarkers will help inform optimal choice of systemic therapy. Summary The management of clinically regional node-positive disease requires a multimodal approach comprising both systemic and local therapy, tailored to the patient and to disease response. While choice of systemic therapy will be informed by ongoing studies in patients with metastatic disease, including the elucidation of predictive biomarkers, the comparative effectiveness of local therapies remains an important evidence gap.